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Article(id=1198602001446695871, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1198601997155922872, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.2255.2023.0604, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1667145600000, receivedDateStr=2022-10-31, revisedDate=null, revisedDateStr=null, acceptedDate=1675353600000, acceptedDateStr=2023-02-03, onlineDate=1763698586093, onlineDateStr=2025-11-21, pubDate=1719504000000, pubDateStr=2024-06-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1763698586093, onlineIssueDateStr=2025-11-21, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1763698586093, creator=13701087609, updateTime=1763698586093, updator=13701087609, issue=Issue{id=1198601997155922872, tenantId=1146029695717560320, journalId=1189873630562394117, year='2024', volume='49', issue='6', pageStart='611', pageEnd='732', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1763698585070, creator=13701087609, updateTime=1763698770557, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1198602775211901122, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1198601997155922872, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1198602775211901123, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1198601997155922872, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=670, endPage=678, ext={EN=ArticleExt(id=1198602001748685768, articleId=1198602001446695871, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Correlation between MDA, AOPP, Nrf2, GSH levels and acute kidney injury after laparoscopic partial nephrectomy, columnId=1190310109000602400, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Clinical Research, runingTitle=null, highlight=null, articleAbstract=

Objective To analyze the correlation of malondialdehyde (MDA), advanced oxidation protein products (AOPP), nuclear factor erythroid-2 related factor 2 (Nrf2), glutathione (GSH) levels with postoperative acute kidney injury (AKI) among patients undergoing laparoscopic partial nephrectomy (LPN). Methods A total of 110 patients with renal cell carcinoma who were admitted to the Department of Urology, the Third Medical Center of Chinese PLA General Hospital from February to August 2022 were included in the study. Patients were divided into AKI group (n=30) and non-AKI group (n=80) based on the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, and then divided into elderly AKI (>65 years old, n=14), middle-aged AKI (50-65 years old, n=16), elderly non-AKI (>65 years old, n=30), and middle-aged non-AKI (50-65 years old, n=50) four sub-groups based on age. Clinical characteristics and laboratory examination data were recorded. Venous blood was collected from the patients before the operation (T1), immediately after the surgery (T2), and 24 h after surgery (T3), and MDA, AOPP, Nrf2 and GSH levels were measured. MDA, AOPP, Nrf2 and GSH levels were compared between the four subgroups at different time points, and their correlation with the occurrence of AKI after LPN were explored. The risk factors for AKI after LPN were analyzed using the univariate and multivariate logistic regression. Results Spearman correlation analysis revealed that AKI was not associated with the MDA level at each time point (P>0.05), was positively associated with AOPP-T3 level (r=0.315, P=0.037), was negatively associated with the Nrf2-T3 level (r=-0.365, P=0.015) and GSH-T2 level (r=-0.338, P=0.025) in elderly patients after LPN. AKI was not associated with MDA, AOPP, Nrf2, and GSH levels (P>0.05) in middle-aged patients after LPN. Multivariate logistic regression analysis showed that BMI (OR=2.724, P=0.040) and surgically resected kidney volume (OR=1.309, P=0.049) were independent risk factors for AKI in elderly patients after LPN, GSH-T2 (OR=0.271, P=0.042) was an independent protective factor for AKI in elderly patients after LPN. Intraoperative colloid fluid intake (OR=1.006, P=0.007) was an independent risk factor for AKI in middle-aged patients after LPN, intraoperative urine output (OR=0.104, P=0.007) was an independent protective factor for AKI in middle-aged patients after LPN. Conclusions The AKI after LPN may be related to the increase of AOPP level and the decrease of Nrf2 and GSH levels in elderly patients, and the postoperative GSH is an independent protective factor for AKI in elderly patients after LPN. The correlation of AKI after LPN is not significant with the levels of MDA, AOPP, Nrf2 and GSH in the middle-aged patients.

, correspAuthors=Yong-Zhe Liu, authorNote=null, correspAuthorsNote=
E-mail:
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目的 分析丙二醛(MDA)、人晚期氧化蛋白产物(AOPP)、血浆核因子E2相关因子(Nrf2)和谷胱甘肽(GSH)水平与肾细胞癌患者腹腔镜肾部分切除术(LPN)后急性肾损伤(AKI)的相关性。方法 纳入2022年2-8月解放军总医院第三医学中心泌尿外科收治的110例肾细胞癌患者。依据国际肾病改善全球预后(KDIGO)标准分为AKI组(n=30)和非AKI组(n=80)，再依据年龄分为老年AKI(>65岁，n=14)、中年AKI(50~65岁，n=16)与老年非AKI(>65岁，n=30)、中年非AKI(50~65岁，n=50) 4个亚组。收集患者的临床资料和实验室检查结果，并于手术开始前(T1)、手术结束后(T2)、术后24 h(T3)采集静脉血，检测MDA、AOPP、Nrf2、GSH水平，比较各亚组不同时间点MDA、AOPP、Nrf2、GSH水平，并分析其与LPN术后AKI发生的相关性，采用单因素和多因素logistic回归分析LPN术后发生AKI的危险因素。结果 Spearman相关分析显示，老年患者各时间点MDA水平与LPN术后AKI的发生无明显相关性(P>0.05)，AOPP-T3水平与LPN术后AKI的发生呈正相关(r=0.315，P=0.037)，Nrf2-T3、GSH-T2水平与LPN术后AKI的发生呈负相关(r=-0.365，P=0.015；r=-0.338，P=0.025)。中年患者各时间点MDA、AOPP、Nrf2、GSH水平与LPN术后AKI的发生无明显相关性(P>0.05)。多因素logistic回归分析显示，BMI、手术切除肾体积是老年患者LPN术后AKI发生的独立危险因素(OR=2.724，P=0.040；OR=1.309，P=0.049)，GSH-T2是老年患者LPN术后AKI发生的独立保护因素(OR=0.271，P=0.042)；术中胶体液入量是中年患者LPN术后AKI发生的独立危险因素(OR=1.006，P=0.007)，术中尿量是中年患者LPN术后AKI发生的独立保护因素(OR=0.104，P=0.007)。结论 老年患者LPN术后AKI的发生可能与术后AOPP水平升高和Nrf2、GSH水平降低有关，且术后GSH是老年患者LPN术后AKI发生的独立保护因素，而中年患者LPN术后AKI的发生则与围手术期MDA、AOPP、Nrf2、GSH水平变化无明显相关性。

, correspAuthors=刘永哲, authorNote=null, correspAuthorsNote=
刘永哲，E-mail：
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董钰妍，硕士研究生，主要从事围手术期器官功能保护方面的研究

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董钰妍，硕士研究生，主要从事围手术期器官功能保护方面的研究

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董钰妍，硕士研究生，主要从事围手术期器官功能保护方面的研究

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Biomed Res Int, 2020, 2020: 5824209., articleTitle=Clinical study of three-dimensional laparoscopic partial nephrectomy for the treatment of highly complex renal tumors with renal nephrometry scores of ≥10 points, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1198602002633683942, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198602001446695871, xref=1, ext=[AuthorCompanyExt(id=1198602002642072551, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198602001446695871, companyId=1198602002633683942, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1College of Anesthesiology, Shanxi Medical University, Taiyuan, Shanxi 030001, China), AuthorCompanyExt(id=1198602002650461160, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198602001446695871, companyId=1198602002633683942, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1山西医科大学麻醉学院，山西太原 030001)]), AuthorCompany(id=1198602003745174511, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198602001446695871, xref=2, ext=[AuthorCompanyExt(id=1198602003753563120, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198602001446695871, companyId=1198602003745174511, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2Department of Anesthesiology, the Third Medical Center of Chinese PLA General Hospital, Beijing 100039, China), AuthorCompanyExt(id=1198602003757757425, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198602001446695871, companyId=1198602003745174511, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2解放军总医院第三医学中心麻醉科，北京 100039)])], figs=[ArticleFig(id=1198602005448060987, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198602001446695871, language=EN, label=Fig.1, caption=Comparison of MDA, AOPP, Nrf2, and GSH levels at different time points of patients with renal cell carcinoma in each group, figureFileSmall=eQLvRyukqvr7+0vj7PZenQ==, figureFileBig=Ffp2MGEHVYzrVl41ilHwog==, tableContent=null), ArticleFig(id=1198602005573890115, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198602001446695871, language=CN, label=图1, caption=各组肾细胞癌患者不同时间点MDA、AOPP、Nrf2、GSH水平比较

MDA. 丙二醛；AOPP. 高级氧化蛋白质产物；Nrf2. 核因子E2相关因子2；GSH. 谷胱甘肽；AKI. 急性肾损伤；T1. 手术开始前；T2. 手术结束后；T3. 术后24 h；A. 老年AKI亚组与老年非AKI亚组不同时间点MDA、AOPP、Nrf2、GSH水平比较；B. 中年AKI亚组与中年非AKI亚组不同时间点MDA、AOPP、Nrf2、GSH水平比较；*P<0.05，**P<0.01，***P<0.001

, figureFileSmall=eQLvRyukqvr7+0vj7PZenQ==, figureFileBig=Ffp2MGEHVYzrVl41ilHwog==, tableContent=null), ArticleFig(id=1198602005787799630, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198602001446695871, language=EN, label=Tab.1, caption=

Comparison of baseline data of patients with renal cell carcinoma in each group

, figureFileSmall=null, figureFileBig=null, tableContent=
指标总体老年中年
AKI组(n=30)非AKI组(n=80)PAKI亚组(n=14)非AKI亚组(n=30)PAKI亚组(n=16)非AKI亚组(n=50)P
年龄[岁, M(Q1, Q3)]61.0(57.0, 66.3)60.5(55.0, 67.0)0.48266.50(65.00, 70.50)68.50(65.75, 71.00)0.35257.50(55.25, 59.00)57.00(53.75, 60.00)0.642
男/女(例)28/252/280.00314/022/80.04114/230/200.042
BMI[kg/m2, M(Q1, Q3)]25.86(22.96, 28.56)23.93(21.85, 25.78)0.00927.37(24.55, 29.38)24.01(22.57, 25.29)0.00223.91(21.96, 28.40)23.90(21.48, 25.85)0.415
吸烟[例(%)]19(63.3)36(45.0)0.0878(57.1)10(33.3)0.13511(68.8)26(52.0)0.240
饮酒[例(%)]13(43.3)20(25.0)0.0616(42.9)6(20.0)0.1137(43.8)14(28.0)0.239
FBG[mmol/L, M(Q1, Q3)]5.37(5.04, 8.06)5.57(5.15, 6.35)0.9685.35(5.17, 6.53)5.57(4.94, 6.86)0.7626.45(4.67, 8.56)5.57(5.17, 6.15)0.875
GSP[μmol/L, M(Q1, Q3)]145.50(135.75, 158.25)149.00(137.00, 159.00)0.650144.50(130.75, 152.75)147.00(133.25, 155.75)0.705149.00(136.00, 166.50)150.00(139.25, 163.00)0.875
Hb[g/L, M(Q1, Q3)]151.00(135.00, 164.36)149.00(136.00, 165.88)0.981144.50(125.75, 169.63)149.50(136.50, 163.63)0.687152.00(142.50, 162.50)148.50(135.75, 169.13)0.703
sCr[μmoI/L, M(Q1, Q3)]75.00(69.75, 87.25)73.00(59.00, 80.75)0.07970.00(69.00, 85.00)73.00(56.00, 80.00)0.72485.50(71.75, 88.00)72.50(62.75, 81.00)0.057
eGFR[ml/min, M(Q1, Q3)]92.32(84.86, 106.17)91.15(77.80, 101.32)0.33792.63(77.92, 111.84)84.23(75.95, 96.89)0.15191.29(86.64, 102.58)93.57(84.39, 103.65)0.976
肾肿瘤体积[cm3, M(Q1, Q3)]4.95(3.62, 12.67)4.76(1.71, 8.58)0.0644.95(2.41, 12.67)4.40(1.51, 8.67)0.1825.73(3.82, 15.38)5.07(1.79, 8.44)0.135
合并疾病[例(%)]
高血压23(76.7)49(61.3)0.13013(92.9)17(56.7)0.04010(62.5)31(62.0)0.971
糖尿病10(33.3)20(25.0)0.3822(14.3)6(20.0)0.9708(50.0)14(28.0)0.104
心血管疾病8(26.7)22(27.5)0.9302(14.3)12(40.0)0.1746(37.5)10(20.0)0.155
), ArticleFig(id=1198602005892657238, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198602001446695871, language=CN, label=表1, caption=

各组肾细胞癌患者基线资料比较

, figureFileSmall=null, figureFileBig=null, tableContent=
指标总体老年中年
AKI组(n=30)非AKI组(n=80)PAKI亚组(n=14)非AKI亚组(n=30)PAKI亚组(n=16)非AKI亚组(n=50)P
年龄[岁, M(Q1, Q3)]61.0(57.0, 66.3)60.5(55.0, 67.0)0.48266.50(65.00, 70.50)68.50(65.75, 71.00)0.35257.50(55.25, 59.00)57.00(53.75, 60.00)0.642
男/女(例)28/252/280.00314/022/80.04114/230/200.042
BMI[kg/m2, M(Q1, Q3)]25.86(22.96, 28.56)23.93(21.85, 25.78)0.00927.37(24.55, 29.38)24.01(22.57, 25.29)0.00223.91(21.96, 28.40)23.90(21.48, 25.85)0.415
吸烟[例(%)]19(63.3)36(45.0)0.0878(57.1)10(33.3)0.13511(68.8)26(52.0)0.240
饮酒[例(%)]13(43.3)20(25.0)0.0616(42.9)6(20.0)0.1137(43.8)14(28.0)0.239
FBG[mmol/L, M(Q1, Q3)]5.37(5.04, 8.06)5.57(5.15, 6.35)0.9685.35(5.17, 6.53)5.57(4.94, 6.86)0.7626.45(4.67, 8.56)5.57(5.17, 6.15)0.875
GSP[μmol/L, M(Q1, Q3)]145.50(135.75, 158.25)149.00(137.00, 159.00)0.650144.50(130.75, 152.75)147.00(133.25, 155.75)0.705149.00(136.00, 166.50)150.00(139.25, 163.00)0.875
Hb[g/L, M(Q1, Q3)]151.00(135.00, 164.36)149.00(136.00, 165.88)0.981144.50(125.75, 169.63)149.50(136.50, 163.63)0.687152.00(142.50, 162.50)148.50(135.75, 169.13)0.703
sCr[μmoI/L, M(Q1, Q3)]75.00(69.75, 87.25)73.00(59.00, 80.75)0.07970.00(69.00, 85.00)73.00(56.00, 80.00)0.72485.50(71.75, 88.00)72.50(62.75, 81.00)0.057
eGFR[ml/min, M(Q1, Q3)]92.32(84.86, 106.17)91.15(77.80, 101.32)0.33792.63(77.92, 111.84)84.23(75.95, 96.89)0.15191.29(86.64, 102.58)93.57(84.39, 103.65)0.976
肾肿瘤体积[cm3, M(Q1, Q3)]4.95(3.62, 12.67)4.76(1.71, 8.58)0.0644.95(2.41, 12.67)4.40(1.51, 8.67)0.1825.73(3.82, 15.38)5.07(1.79, 8.44)0.135
合并疾病[例(%)]
高血压23(76.7)49(61.3)0.13013(92.9)17(56.7)0.04010(62.5)31(62.0)0.971
糖尿病10(33.3)20(25.0)0.3822(14.3)6(20.0)0.9708(50.0)14(28.0)0.104
心血管疾病8(26.7)22(27.5)0.9302(14.3)12(40.0)0.1746(37.5)10(20.0)0.155
), ArticleFig(id=1198602005993320541, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198602001446695871, language=EN, label=Tab.2, caption=

Comparison of MDA, AOPP, Nrf2, and GSH levels at different time points of patients with renal cell carcinoma in the two group (μmol/L, $\bar{x}±s$)

, figureFileSmall=null, figureFileBig=null, tableContent=
指标AKI组(n=30)非AKI组(n=80)P
MDA
T11.69±0.561.84±0.900.026
T22.39±1.152.23±1.280.897
T32.71±1.162.39±1.010.499
AOPP
T138.11±8.8538.14±9.460.958
T241.55±9.6740.84±8.650.278
T343.96±6.5640.62±8.810.128
Nrf2
T11088.93±189.471151.04±152.520.043
T21128.16±178.171133.14±115.080.026
T31058.44±205.471118.27±176.680.148
GSH
T111.53±3.1311.86±2.660.153
T210.14±2.9611.10±2.900.881
T310.43±3.0311.11±2.900.535
), ArticleFig(id=1198602006110761063, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198602001446695871, language=CN, label=表2, caption=

两组肾细胞癌患者不同时间点MDA、AOPP、Nrf2、GSH水平比较(μmol/L， $\bar{x}±s$)

, figureFileSmall=null, figureFileBig=null, tableContent=
指标AKI组(n=30)非AKI组(n=80)P
MDA
T11.69±0.561.84±0.900.026
T22.39±1.152.23±1.280.897
T32.71±1.162.39±1.010.499
AOPP
T138.11±8.8538.14±9.460.958
T241.55±9.6740.84±8.650.278
T343.96±6.5640.62±8.810.128
Nrf2
T11088.93±189.471151.04±152.520.043
T21128.16±178.171133.14±115.080.026
T31058.44±205.471118.27±176.680.148
GSH
T111.53±3.1311.86±2.660.153
T210.14±2.9611.10±2.900.881
T310.43±3.0311.11±2.900.535
), ArticleFig(id=1198602006244978802, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198602001446695871, language=EN, label=Tab.3, caption=

Correlation analysis of MDA, AOPP, Nrf2, GSH kevels and AKI at different time points of elderly and middle-aged patients with renal cell carcinoma

, figureFileSmall=null, figureFileBig=null, tableContent=
指标老年中年
rPrP
MDA
T10.0420.785-0.0710.574
T20.7860.185-0.0550.662
T30.2670.080-0.0010.994
AOPP
T1-0.0810.6030.2040.100
T2-0.0850.5850.0460.711
T30.3150.0370.0580.646
Nrf2
T1-0.0420.785-0.1090.381
T2-0.2650.0820.1470.240
T3-0.3650.0150.0060.965
GSH
T1-0.2310.1320.0500.689
T2-0.3380.0250.0540.668
T3-0.2810.0650.0330.790
), ArticleFig(id=1198602006391779450, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198602001446695871, language=CN, label=表3, caption=

老年和中年肾细胞癌患者不同时间点MDA、AOPP、Nrf2、GSH水平与AKI的相关性分析

, figureFileSmall=null, figureFileBig=null, tableContent=
指标老年中年
rPrP
MDA
T10.0420.785-0.0710.574
T20.7860.185-0.0550.662
T30.2670.080-0.0010.994
AOPP
T1-0.0810.6030.2040.100
T2-0.0850.5850.0460.711
T30.3150.0370.0580.646
Nrf2
T1-0.0420.785-0.1090.381
T2-0.2650.0820.1470.240
T3-0.3650.0150.0060.965
GSH
T1-0.2310.1320.0500.689
T2-0.3380.0250.0540.668
T3-0.2810.0650.0330.790
), ArticleFig(id=1198602006576328831, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198602001446695871, language=EN, label=Tab.4, caption=

Comparison of perioperative indexes of patients with renal cell carcinoma in each group [M(Q1, Q3)]

, figureFileSmall=null, figureFileBig=null, tableContent=
指标总体老年中年
AKI组(n=30)非AKI组(n=80)PAKI亚组(n=14)非AKI亚组(n=30)PAKI亚组(n=16)非AKI亚组(n=50)P
手术时间(h)2.67(2.31, 3.04)2.53(2.00, 3.00)0.1052.71(2.48, 2.94)2.29(2.00, 3.00)0.0752.54(2.12, 3.23)2.58(1.83, 3.09)0.423
肾动脉阻断时间(min)28.00(25.75, 32.25)22.00(15.00, 28.00)0.00127.00(23.75, 30.50)19.00(14.75, 25.25)0.00528.50(26.00, 33.75)24.50(17.00, 31.00)0.030
术中心率(次/min)56.99(51.83, 61.29)57.80(52.40, 65.15)0.35456.30(52.15, 61.44)59.26(52.87, 65.45)0.31356.99(51.48, 62.48)56.35(52.15, 64.16)0.659
术中平均动脉压(mmHg)83.35(80.50, 89.11)87.00(81.00, 92.75)0.21483.85(81.09, 87.75)87.00(80.75, 94.00)0.59682.50(79.00, 89.34)87.00(80.86, 91.03)0.284
术中晶体液入量(ml)1500.00(1500.00, 2000.00)1500.00(1500.00, 1937.50)0.4251500.00(1500.00, 2000.00)1500.00(1500.00, 1812.50)0.7801500.00(1500.00, 2000.00)1500.00(1500.00, 2000.00)0.399
术中胶体液入量(ml)500.00(500.00, 500.00)500.00(0.00, 500.00)0.000500.00(500.00, 500.00)500.00(375.00, 500.00)0.049500.00(500.00, 500.00)500.00(0, 500.00)0.003
术中出血量(ml)50.00(50.00, 50.00)50.00(50.00, 50.00)0.24950.00(50.00, 50.00)50.00(50.00, 50.00)0.69850.00(50.00, 50.00)50.00(50.00, 50.00)0.348
术中尿量[ml/(kg·h)]0.61(0.42, 0.72)1.03(0.64, 1.52)0.0000.61(0.46, 0.75)1.14(0.62, 1.30)0.0040.61(0.31, 0.68)0.98(0.66, 2.01)0.000
手术切除肾体积(cm3)17.84(14.01, 30.17)9.02(5.81, 16.99)0.00116.10(11.24, 29.87)7.64(3.82, 13.33)0.00519.86(14.63, 31.63)9.67(6.78, 18.77)0.031
切除正常肾体积(cm3)11.15(6.79, 16.08)4.42(2.75, 8.36)0.00110.61(3.10, 16.83)2.98(1.53, 5.80)0.00814.13(7.65, 15.75)5.41(3.10, 9.27)0.007
), ArticleFig(id=1198602006693769352, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198602001446695871, language=CN, label=表4, caption=

各组肾细胞癌患者围手术期指标比较[M(Q1, Q3)]

, figureFileSmall=null, figureFileBig=null, tableContent=
指标总体老年中年
AKI组(n=30)非AKI组(n=80)PAKI亚组(n=14)非AKI亚组(n=30)PAKI亚组(n=16)非AKI亚组(n=50)P
手术时间(h)2.67(2.31, 3.04)2.53(2.00, 3.00)0.1052.71(2.48, 2.94)2.29(2.00, 3.00)0.0752.54(2.12, 3.23)2.58(1.83, 3.09)0.423
肾动脉阻断时间(min)28.00(25.75, 32.25)22.00(15.00, 28.00)0.00127.00(23.75, 30.50)19.00(14.75, 25.25)0.00528.50(26.00, 33.75)24.50(17.00, 31.00)0.030
术中心率(次/min)56.99(51.83, 61.29)57.80(52.40, 65.15)0.35456.30(52.15, 61.44)59.26(52.87, 65.45)0.31356.99(51.48, 62.48)56.35(52.15, 64.16)0.659
术中平均动脉压(mmHg)83.35(80.50, 89.11)87.00(81.00, 92.75)0.21483.85(81.09, 87.75)87.00(80.75, 94.00)0.59682.50(79.00, 89.34)87.00(80.86, 91.03)0.284
术中晶体液入量(ml)1500.00(1500.00, 2000.00)1500.00(1500.00, 1937.50)0.4251500.00(1500.00, 2000.00)1500.00(1500.00, 1812.50)0.7801500.00(1500.00, 2000.00)1500.00(1500.00, 2000.00)0.399
术中胶体液入量(ml)500.00(500.00, 500.00)500.00(0.00, 500.00)0.000500.00(500.00, 500.00)500.00(375.00, 500.00)0.049500.00(500.00, 500.00)500.00(0, 500.00)0.003
术中出血量(ml)50.00(50.00, 50.00)50.00(50.00, 50.00)0.24950.00(50.00, 50.00)50.00(50.00, 50.00)0.69850.00(50.00, 50.00)50.00(50.00, 50.00)0.348
术中尿量[ml/(kg·h)]0.61(0.42, 0.72)1.03(0.64, 1.52)0.0000.61(0.46, 0.75)1.14(0.62, 1.30)0.0040.61(0.31, 0.68)0.98(0.66, 2.01)0.000
手术切除肾体积(cm3)17.84(14.01, 30.17)9.02(5.81, 16.99)0.00116.10(11.24, 29.87)7.64(3.82, 13.33)0.00519.86(14.63, 31.63)9.67(6.78, 18.77)0.031
切除正常肾体积(cm3)11.15(6.79, 16.08)4.42(2.75, 8.36)0.00110.61(3.10, 16.83)2.98(1.53, 5.80)0.00814.13(7.65, 15.75)5.41(3.10, 9.27)0.007
), ArticleFig(id=1198602006781849742, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198602001446695871, language=EN, label=Tab.5, caption=

Univariate logistic regression analysis of risk factors for the AKI in renal cell carcinoma patients after LPN

, figureFileSmall=null, figureFileBig=null, tableContent=
因素βWald χ2OR95%CIP
老年患者
BMI0.4517.9891.5701.148~2.1470.005
肾动脉阻断时间(参考：无)0.0763.4871.0790.996~1.1680.062
术中胶体液入量0.0043.2301.0041.000~1.0080.072
术中尿量-3.6016.8850.0270.002~0.4020.009
手术切除肾体积0.1087.5971.1141.032~1.2030.006
切除正常肾体积0.1556.7061.1671.038~1.3120.010
MDA-T30.6733.6461.9610.982~3.9150.056
AOPP-T30.1084.4771.1141.008~1.2320.034
Nrf2-T3-0.0065.5230.9940.989~0.9990.019
GSH-T2-0.2744.4930.7600.590~0.9800.034
中年患者
男性(参考：女性)-1.5403.6240.2140.044~1.0470.057
肾动脉阻断时间(参考：无)0.0432.3041.0440.987~1.1040.129
术中胶体液入量0.0056.0501.0051.001~1.0090.014
术中尿量-2.0925.7630.1230.022~0.6810.016
手术切除肾体积0.0443.6351.0450.999~1.0940.057
切除正常肾体积0.0703.8081.0731.000~1.1510.051
), ArticleFig(id=1198602006882513046, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198602001446695871, language=CN, label=表5, caption=

单因素logistic回归分析肾细胞癌患者LPN术后AKI发生的影响因素

, figureFileSmall=null, figureFileBig=null, tableContent=
因素βWald χ2OR95%CIP
老年患者
BMI0.4517.9891.5701.148~2.1470.005
肾动脉阻断时间(参考：无)0.0763.4871.0790.996~1.1680.062
术中胶体液入量0.0043.2301.0041.000~1.0080.072
术中尿量-3.6016.8850.0270.002~0.4020.009
手术切除肾体积0.1087.5971.1141.032~1.2030.006
切除正常肾体积0.1556.7061.1671.038~1.3120.010
MDA-T30.6733.6461.9610.982~3.9150.056
AOPP-T30.1084.4771.1141.008~1.2320.034
Nrf2-T3-0.0065.5230.9940.989~0.9990.019
GSH-T2-0.2744.4930.7600.590~0.9800.034
中年患者
男性(参考：女性)-1.5403.6240.2140.044~1.0470.057
肾动脉阻断时间(参考：无)0.0432.3041.0440.987~1.1040.129
术中胶体液入量0.0056.0501.0051.001~1.0090.014
术中尿量-2.0925.7630.1230.022~0.6810.016
手术切除肾体积0.0443.6351.0450.999~1.0940.057
切除正常肾体积0.0703.8081.0731.000~1.1510.051
), ArticleFig(id=1198602007008342174, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198602001446695871, language=EN, label=Tab.6, caption=

Multivariate logistic regression analysis of risk factors for the AKI in renal cell carcinoma patients after LPN

, figureFileSmall=null, figureFileBig=null, tableContent=
因素βWald χ2OR95%CIP
老年患者
BMI1.0024.2152.7241.047~7.0920.040
术中尿量-7.3512.7380.0010.000~3.8790.098
手术切除肾体积0.2693.8891.3091.002~1.7090.049
AOPP-T30.2993.1891.3490.971~1.8730.074
Nrf2-T3-0.0142.1530.9860.968~1.0050.142
GSH-T2-1.3054.1550.2710.077~0.9510.042
中年患者
术中胶体液入量0.0067.3491.0061.002~1.0100.007
术中尿量-2.2657.1760.1040.020~0.5440.007
), ArticleFig(id=1198602007100616866, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1198602001446695871, language=CN, label=表6, caption=

多因素logistic回归分析肾细胞癌患者LPN术后AKI发生的影响因素

, figureFileSmall=null, figureFileBig=null, tableContent=
因素βWald χ2OR95%CIP
老年患者
BMI1.0024.2152.7241.047~7.0920.040
术中尿量-7.3512.7380.0010.000~3.8790.098
手术切除肾体积0.2693.8891.3091.002~1.7090.049
AOPP-T30.2993.1891.3490.971~1.8730.074
Nrf2-T3-0.0142.1530.9860.968~1.0050.142
GSH-T2-1.3054.1550.2710.077~0.9510.042
中年患者
术中胶体液入量0.0067.3491.0061.002~1.0100.007
术中尿量-2.2657.1760.1040.020~0.5440.007
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MDA、AOPP、Nrf2、GSH水平与肾细胞癌患者腹腔镜肾部分切除术后急性肾损伤的相关性
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董钰妍 1 , 刘永哲 1, 2, *
解放军医学杂志 | 临床研究 2024,49(6): 670-678
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解放军医学杂志 | 临床研究 2024, 49(6): 670-678
MDA、AOPP、Nrf2、GSH水平与肾细胞癌患者腹腔镜肾部分切除术后急性肾损伤的相关性
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董钰妍1, 刘永哲1, 2, *
作者信息
  • 1山西医科大学麻醉学院，山西太原 030001
  • 2解放军总医院第三医学中心麻醉科，北京 100039

    • 董钰妍，硕士研究生，主要从事围手术期器官功能保护方面的研究

通讯作者:

刘永哲，E-mail：
Correlation between MDA, AOPP, Nrf2, GSH levels and acute kidney injury after laparoscopic partial nephrectomy
Yu-Yan Dong1, Yong-Zhe Liu1, 2, *
Affiliations
  • 1College of Anesthesiology, Shanxi Medical University, Taiyuan, Shanxi 030001, China
  • 2Department of Anesthesiology, the Third Medical Center of Chinese PLA General Hospital, Beijing 100039, China
出版时间: 2024-06-28 doi: 10.11855/j.issn.0577-7402.2255.2023.0604
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摘要
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目的 分析丙二醛(MDA)、人晚期氧化蛋白产物(AOPP)、血浆核因子E2相关因子(Nrf2)和谷胱甘肽(GSH)水平与肾细胞癌患者腹腔镜肾部分切除术(LPN)后急性肾损伤(AKI)的相关性。方法 纳入2022年2-8月解放军总医院第三医学中心泌尿外科收治的110例肾细胞癌患者。依据国际肾病改善全球预后(KDIGO)标准分为AKI组(n=30)和非AKI组(n=80)，再依据年龄分为老年AKI(>65岁，n=14)、中年AKI(50~65岁，n=16)与老年非AKI(>65岁，n=30)、中年非AKI(50~65岁，n=50) 4个亚组。收集患者的临床资料和实验室检查结果，并于手术开始前(T1)、手术结束后(T2)、术后24 h(T3)采集静脉血，检测MDA、AOPP、Nrf2、GSH水平，比较各亚组不同时间点MDA、AOPP、Nrf2、GSH水平，并分析其与LPN术后AKI发生的相关性，采用单因素和多因素logistic回归分析LPN术后发生AKI的危险因素。结果 Spearman相关分析显示，老年患者各时间点MDA水平与LPN术后AKI的发生无明显相关性(P>0.05)，AOPP-T3水平与LPN术后AKI的发生呈正相关(r=0.315，P=0.037)，Nrf2-T3、GSH-T2水平与LPN术后AKI的发生呈负相关(r=-0.365，P=0.015；r=-0.338，P=0.025)。中年患者各时间点MDA、AOPP、Nrf2、GSH水平与LPN术后AKI的发生无明显相关性(P>0.05)。多因素logistic回归分析显示，BMI、手术切除肾体积是老年患者LPN术后AKI发生的独立危险因素(OR=2.724，P=0.040；OR=1.309，P=0.049)，GSH-T2是老年患者LPN术后AKI发生的独立保护因素(OR=0.271，P=0.042)；术中胶体液入量是中年患者LPN术后AKI发生的独立危险因素(OR=1.006，P=0.007)，术中尿量是中年患者LPN术后AKI发生的独立保护因素(OR=0.104，P=0.007)。结论 老年患者LPN术后AKI的发生可能与术后AOPP水平升高和Nrf2、GSH水平降低有关，且术后GSH是老年患者LPN术后AKI发生的独立保护因素，而中年患者LPN术后AKI的发生则与围手术期MDA、AOPP、Nrf2、GSH水平变化无明显相关性。

腹腔镜  /  肾部分切除术  /  急性肾损伤  /  核因子E2相关因子  /  谷胱甘肽

Objective To analyze the correlation of malondialdehyde (MDA), advanced oxidation protein products (AOPP), nuclear factor erythroid-2 related factor 2 (Nrf2), glutathione (GSH) levels with postoperative acute kidney injury (AKI) among patients undergoing laparoscopic partial nephrectomy (LPN). Methods A total of 110 patients with renal cell carcinoma who were admitted to the Department of Urology, the Third Medical Center of Chinese PLA General Hospital from February to August 2022 were included in the study. Patients were divided into AKI group (n=30) and non-AKI group (n=80) based on the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, and then divided into elderly AKI (>65 years old, n=14), middle-aged AKI (50-65 years old, n=16), elderly non-AKI (>65 years old, n=30), and middle-aged non-AKI (50-65 years old, n=50) four sub-groups based on age. Clinical characteristics and laboratory examination data were recorded. Venous blood was collected from the patients before the operation (T1), immediately after the surgery (T2), and 24 h after surgery (T3), and MDA, AOPP, Nrf2 and GSH levels were measured. MDA, AOPP, Nrf2 and GSH levels were compared between the four subgroups at different time points, and their correlation with the occurrence of AKI after LPN were explored. The risk factors for AKI after LPN were analyzed using the univariate and multivariate logistic regression. Results Spearman correlation analysis revealed that AKI was not associated with the MDA level at each time point (P>0.05), was positively associated with AOPP-T3 level (r=0.315, P=0.037), was negatively associated with the Nrf2-T3 level (r=-0.365, P=0.015) and GSH-T2 level (r=-0.338, P=0.025) in elderly patients after LPN. AKI was not associated with MDA, AOPP, Nrf2, and GSH levels (P>0.05) in middle-aged patients after LPN. Multivariate logistic regression analysis showed that BMI (OR=2.724, P=0.040) and surgically resected kidney volume (OR=1.309, P=0.049) were independent risk factors for AKI in elderly patients after LPN, GSH-T2 (OR=0.271, P=0.042) was an independent protective factor for AKI in elderly patients after LPN. Intraoperative colloid fluid intake (OR=1.006, P=0.007) was an independent risk factor for AKI in middle-aged patients after LPN, intraoperative urine output (OR=0.104, P=0.007) was an independent protective factor for AKI in middle-aged patients after LPN. Conclusions The AKI after LPN may be related to the increase of AOPP level and the decrease of Nrf2 and GSH levels in elderly patients, and the postoperative GSH is an independent protective factor for AKI in elderly patients after LPN. The correlation of AKI after LPN is not significant with the levels of MDA, AOPP, Nrf2 and GSH in the middle-aged patients.

laparoscopic  /  partial nephrectomy  /  acute kidney injury  /  nuclear factor erythroid-2 related factor 2  /  glutathione
董钰妍, 刘永哲. MDA、AOPP、Nrf2、GSH水平与肾细胞癌患者腹腔镜肾部分切除术后急性肾损伤的相关性. 解放军医学杂志, 2024 , 49 (6) : 670 -678 . DOI: 10.11855/j.issn.0577-7402.2255.2023.0604
Yu-Yan Dong, Yong-Zhe Liu. Correlation between MDA, AOPP, Nrf2, GSH levels and acute kidney injury after laparoscopic partial nephrectomy[J]. Medical Journal of Chinese People’s Liberation Army, 2024 , 49 (6) : 670 -678 . DOI: 10.11855/j.issn.0577-7402.2255.2023.0604
正文
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腹腔镜肾部分切除术(laparoscopic partial neph-rectomy，LPN)是国际泌尿外科指南推荐的治疗T1期和部分T2期肾细胞癌的金标准[1]。LPN手术期间通常夹闭肾动脉阻断血流，当肿瘤较大、结构复杂或实质浸润较深时，可为肿瘤切除和缝合提供更好的视野，但长时间缺血/再灌注(ischemia/reperfusion，I/R)可通过活性氧(reactive oxygen species，ROS)过度产生、炎症、微循环障碍和线粒体损伤等机制，诱发急性肾损伤(acute kidney injury，AKI)，而氧化应激在这一过程中起着核心作用[2-3]。丙二醛(malondi-aldehyde，MDA)和人晚期氧化蛋白产物(advanced oxidation protein products，AOPP)均为ROS攻击的产物，可作为氧化应激标志物[4-5]，多项动物研究证实肾损伤过程中伴随MDA和AOPP水平显著增高[6-7]。核因子E2相关因子2(nuclear factor erythroid-2 related factor 2，Nrf2)是细胞内源性抗氧化系统的核心调节因子之一[8]，在应激状态下可易位进入细胞核并结合抗氧化反应原件，激活下游抗氧化剂并调控谷胱甘肽(glutathione，GSH)的合成[9-10]，GSH可直接有效地清除ROS[11]。Nrf2/GSH信号通路可反映机体抗氧化防御的能力，有动物研究证实其对肾具有保护作用[12-13]。衰老可引起机体ROS及氧化应激产物逐渐增加，内源性抗氧化防御能力逐渐下降，导致机体氧化/抗氧化系统失衡和严重的器官功能障碍[14-15]。虽然目前已有关于氧化应激/抗氧化水平对AKI影响的动物研究，但针对不同年龄段机体氧化应激/抗氧化水平与术后AKI的相关临床研究较少，基于此，本研究分析不同年龄段肾细胞癌患者机体MDA、AOPP、Nrf2、GSH水平与LPN术后AKI的相关性。
1 资料与方法
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1.1 研究对象
本研究为临床病例对照研究，经解放军总医院第三医学中心医学伦理委员会批准(KY2021-022)，所有受试者均签署知情同意书。纳入2022年2-8月在解放军总医院第三医学中心泌尿外科行择期LPN术的110例肾细胞癌患者。纳入标准：(1)年龄不限；(2)美国麻醉医师协会(American Society of Anesthesiologists，ASA)分级Ⅰ-Ⅱ级；(3)术前血清肌酐(serum creatinine，SCr)<133 μmol/L；(4)估计肾小球滤过率(estimated glomerular filtration rate，eGFR)≥60 ml/min。排除标准：(1)术前有肾手术史；(2)慢性肾病史；(3)围手术期重要脏器功能障碍。最终纳入的所有研究对象年龄均在50岁以上，术后依据改善全球肾病预后组织(Kidney Disease： Improving Global Outcomes，KDIGO)指南诊断标准分为AKI组(n=30)与非AKI组(n=80)，再按照年龄(>65岁或≤65岁)分为4个亚组：[老年AKI(>65岁，n=14)、中年AKI(≤65岁，n=16)、老年非AKI(>65岁，n=30)、中年非AKI(≤65岁，n=50)]。
1.2 麻醉方法
患者入室后建立外周静脉通路，连接监护仪，局麻下行桡动脉穿刺。麻醉诱导：咪达唑仑0.03 mg/kg、舒芬太尼0.5 μg/kg、依托咪酯0.3 mg/kg、顺式阿曲库铵0.2 mg/kg。呼吸机参数：新鲜气体流量2 L/min，潮气量8~10 ml/kg，呼吸频率12~20次/min，吸呼比1:2，吸入氧浓度60%。麻醉维持：中长链丙泊酚4~12 mg/(kg.h)，瑞芬太尼5~15 μg/(kg.h)，七氟醚1%~2%，根据手术情况追加舒芬太尼和顺式阿曲库铵。围手术期采用去氧肾上腺素或麻黄碱维持平均动脉压在基础值的±20%。术后静脉镇痛采用羟考酮0.6 mg/kg、昂丹司琼0.4 mg/kg、地塞米松5 mg，生理盐水配制100 ml，背景剂量2 ml/h，Bolus 0.5 ml，锁定时间15 min。围手术期所有患者均未使用非甾体抗炎药。
1.3 临床资料收集
收集患者的年龄、性别、体重指数(body mass index，BMI)、ASA分级、合并疾病(如高血压、糖尿病、心血管疾病等)，术前空腹血糖(fasting blood-glucose，FBG)、糖化血清蛋白(glycated serum protein，GSP)、血红蛋白(hemoglobin，Hb)水平，术前及术后24 h SCr水平，术中情况(包括手术时间、肾动脉阻断时间、心率、平均动脉压、晶体液入量、胶体液入量、出血量、尿量)，以及术后病理报告等。应用Cockcroft-Gault公式估算eGFR：男性eGFR(ml/min)=(140-年龄)×体重(kg)/[0.818×SCr(μmol/L)]；女性eGFR(ml/min)=eGFR(男性)×0.85。应用椭圆体体积计算公式计算肿瘤体积和手术切除肾体积。V=4π(abc)/3(a、b、c为椭球最大半径)。切除正常肾体积=手术切除肾体积-肿瘤体积。
1.4 生物标志物检测
手术开始前(T1)、手术结束后(T2)、术后24 h(T3)采集患者静脉血，于1 h内3000 r/min(离心半径117 mm)离心10 min，取上层血浆分装入冻存管，于-80 ℃冰箱备存。采用硫代巴比妥酸法检测血浆MDA水平，酶联免疫吸附法检测血浆AOPP、Nrf2和GSH水平。试剂盒购自南京建成科技有限公司，所有操作按照试剂盒说明书进行。
1.5 AKI诊断标准及分期
根据KDIGO指南诊断标准：术后48 h内SCr上升≥26.5 μmol/L或7 d内SCr上升至基线值的1.5倍，或尿量<0.5 ml/(kg·h)持续6 h及以上即诊断为AKI。
AKI分为Ⅰ-Ⅲ期：Ⅰ期，48 h内SCr上升≥26.5 μmol/L和(或)SCr≥基线值的1.5倍，7 d内尿量<0.5 ml/(kg.h)持续6~12 h；Ⅱ期，SCr≥基线值的2倍，尿量<0.5 ml/(kg.h)持续≥12 h；Ⅲ期，SCr≥基线值的3倍或上升至≥353.6 μmol/L或开始肾替代治疗，尿量<0.3 ml/(kg.h)持续≥24 h或无尿≥12 h。
1.6 LPN术后AKI发生与MDA、AOPP、Nrf2、GSH水平的相关性分析
采用Spearman相关分析老年和中年肾细胞癌患者LPN术后AKI发生与MDA、AOPP、Nrf2、GSH水平的相关性。
1.7 LPN术后AKI发生的危险因素分析
采用单因素和多因素logistic回归分析老年和中年肾细胞癌患者LPN术后AKI发生的危险因素。
1.8 统计学处理
采用SPSS 26.0软件进行统计分析。符合正态分布的计量资料以$\bar{x}±s$表示，两组间比较采用两独立样本t检验，组内不同时间点各指标比较采用重复测量的方差分析，并采用Bonferroni检验进行事后两两比较，并将P值经Bonferroni校正；非正态分布的计量资料以M(Q1，Q3)表示，两组间比较采用两独立样本秩和检验；计数资料以例(%)表示，两组间比较采用Pearson χ2检验或Fisher确切概率法。P<0.05为差异有统计学意义。
2 结果
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2.1 各组基线资料比较
共纳入肾细胞癌患者110例，其中30例(27.3%)术后发生AKI，均为I期AKI。老年患者44例，AKI发生率为31.8%(14/44)；中年患者66例，AKI发生率为24.2%(16/66)；老年与中年患者AKI发生率差异无统计学意义(P>0.05，表1)。
AKI组与非AKI组性别、BMI差异有统计学意义(P<0.05)，年龄，吸烟、饮酒比例，FBG、GSP、Hb、sCr、eGFR水平，肾肿瘤体积，以及合并疾病比例差异均无统计学意义(P>0.05，表1)。
老年AKI亚组与老年非AKI亚组性别、BMI、合并高血压比例差异有统计学意义(P<0.05)，其余变量差异均无统计学意义(P>0.05)。中年AKI亚组与中年非AKI亚组性别差异有统计学意义(P<0.05)，其余变量差异均无统计学意义(P>0.05) (表1)。
2.2 各组不同时间点MDA、AOPP、Nrf2、GSH水平比较
与非AKI组比较，AKI组T1时MDA和T1、T2时Nrf2水平明显降低(P<0.05)，其余时间点MDA、Nrf2以及各时间点AOPP、GSH水平差异均无统计学意义(P>0.05，表2)。
与老年非AKI亚组比较，老年AKI亚组T3时MDA、AOPP水平明显升高(P<0.05)，Nrf2水平明显降低(P<0.01)，T2、T3时GSH水平明显降低(P<0.05)。与中年非AKI亚组比较，中年AKI亚组T1、T2、T3时MDA、AOPP、Nrf2、GSH水平差异均无统计学意义(P>0.05) (图1A、B)。
与T1时比较，老年AKI亚组T2、T3时MDA、AOPP水平明显增高(Bonferroni校正P<0.05或Bonferroni校正P<0.01)，T2时GSH水平明显降低(Bonferroni校正P<0.05)；老年非AKI亚组T2、T3时MDA水平明显增高(Bonferroni校正P<0.01或Bonferroni校正P<0.001)，但AOPP、Nrf2、GSH水平均无明显变化(Bonferroni校正P>0.05)。与T1时比较，中年AKI亚组和中年非AKI亚组T2、T3时MDA、AOPP、Nrf2、GSH水平均无明显变化(Bonferroni校正P>0.05) (图1A、B)。
与T2时比较，老年AKI亚组T3时Nrf2水平明显降低(Bonferroni校正P<0.05)，T3时MDA、AOPP、GSH水平无明显变化(Bonferroni校正P>0.05)；老年非AKI亚组、中年AKI亚组、中年非AKI亚组T3时MDA、AOPP、Nrf2、GSH水平均无明显变化(Bonferroni校正P>0.05) (图1A、B)。
2.3 老年与中年肾细胞癌患者不同时间点MDA、AOPP、Nrf2、GSH水平与AKI的相关性分析
Spearman相关分析显示，老年肾细胞癌患者T1–T3各时间点MDA水平与LPN术后AKI发生无明显相关性(P>0.05)，AOPP-T3水平与LPN术后AKI的发生呈正相关(r=0.315，P=0.037)，Nrf2-T3、GSH-T2水平与LPN术后AKI的发生呈负相关(r=-0.365，P=0.015；r=-0.338，P=0.025)。中年肾细胞癌患者T1–T3各时间点MDA、AOPP、Nrf2、GSH水平与LPN术后AKI的发生无明显相关性(P>0.05) (表3)。
2.4 各组围手术期指标比较
AKI组与非AKI组肾动脉阻断时间、术中胶体液入量、术中尿量、手术切除肾体积和切除正常肾体积差异有统计学意义(P<0.05)，其余变量差异均无统计学意义(P>0.05，表4)。
老年AKI亚组与老年非AKI亚组肾动脉阻断时间、术中胶体液入量、术中尿量、手术切除肾体积和切除正常肾体积差异有统计学意义(P<0.05)，其余变量差异均无统计学意义(P>0.05)。中年AKI亚组与中年非AKI亚组肾动脉阻断时间、术中胶体液入量、术中尿量、手术切除肾体积和切除正常肾体积差异有统计学意义(P<0.05)，其余变量差异均无统计学意义(P>0.05，表4)。
2.5 肾细胞癌患者LPN术后AKI发生的影响因素分析
老年肾细胞癌患者性别和高血压分布严重不均匀，影响数据质量，故将其移除。单因素logistic回归分析结果显示，BMI(OR=1.570，P=0.005)、手术切除肾体积(OR=1.114，P=0.006)、切除正常肾体积(OR=1.167，P=0.010)和AOPP-T3(OR=1.114，P=0.034)是老年肾细胞癌患者术后AKI发生的危险因素，术中尿量(OR=0.027，P=0.009)、Nrf2-T3(OR=0.994，P=0.019)和GSH-T2(OR=0.760，P=0.034)是老年肾细胞癌患者术后AKI发生的保护因素；术中胶体液入量(OR=1.005，P=0.014)是中年肾细胞癌患者术后AKI发生的危险因素，术中尿量(OR=0.123，P=0.016)是中年肾细胞癌患者术后AKI发生的保护因素(表5)。
老年肾细胞癌患者手术切除肾体积与切除正常肾体积有明显相关性(P=0.000)，故移除切除正常肾体积。多因素logistic回归分析结果显示，BMI(OR=2.724，P=0.040)和手术切除肾体积(OR=1.309，P=0.049)是老年肾细胞癌患者LPN术后AKI发生的独立危险因素，GSH-T2(OR=0.271，P=0.042)是老年肾细胞癌患者LPN术后AKI发生的独立保护因素；术中胶体液入量(OR=1.006，P=0.007)是中年肾细胞癌患者LPN术后AKI发生的独立危险因素，术中尿量(OR=0.104，P=0.007)是中年肾细胞癌患者LPN术后AKI发生的独立保护因素(表6)。
3 讨论
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肾脏I/R损伤和外科手术操作创伤导致的缺氧和氧化应激是LPN术后AKI发生的主要原因之一[16]。老年患者机体ROS产生及氧化应激产物较青年患者多且差异大，内源性抗氧化系统活力下降，易造成机体氧化/抗氧化系统失调，从而导致细胞功能损伤甚至丧失[15]。本研究分析不同年龄段肾细胞癌患者发现，老年患者LPN术后AKI的发生可能与术后AOPP水平升高和Nrf2、GSH水平降低有关，而中年患者LPN术后AKI的发生则与围手术期MDA、AOPP、Nrf2、GSH水平变化无明显相关性。
既往研究发现，肾部分切除术后AKI的发生率为16.5%~54.0%[17-18]，本研究中LPN术后AKI发生率为27.3%(30/110)，且均为I期AKI，其中65岁以上患者AKI发生率为31.8%，50~65岁患者为24.2%，该结果与既往研究一致。老年患者术后AKI发生率稍高于中年患者，但差异无统计学意义，分析原因可能与样本量不足有关，应扩大研究进一步验证。
MDA是ROS与多不饱和脂肪酸、花生四烯酸等脂质反应的最终产物，可作为氧化应激标志物[4]，Jawad等[6]发现，I/R可引起ROS暴发致使肾氧化还原状态失衡，导致肾结构和功能性肾小管细胞受损，肾组织MDA水平随之明显增高。AOPP是体内血浆蛋白被ROS攻击后氧化修饰形成的双酪氨酸蛋白复合物[5]，在预测氧化应激方面较脂质过氧化产物更灵敏、准确，更适合反映急性氧化应激过程[19]。Gyurászová等[7]发现，切除大鼠双侧肾诱导AKI，手术组术后48 h血浆AOPP水平明显高于假手术组。Du等[20]发现，AOPP参与缺血性AKI的病理生理过程，且其水平升高与ICU患者的AKI严重程度相关。本研究结果显示，AKI组术前MDA水平较非AKI组降低，分组分析显示，与术前相比，老年AKI亚组术后MDA、AOPP水平均明显升高，而老年非AKI亚组、中年AKI亚组和中年非AKI亚组术后MDA、AOPP水平无明显变化，AOPP水平仅在老年AKI亚组术后升高可能与老年AKI患者机体氧化应激和肾损伤程度更严重有关。Spearman相关分析显示，老年患者LPN术后AKI的发生与术后AOPP水平升高呈正相关，与MDA水平无明显相关性，而中年患者LPN术后AKI的发生与围手术期MDA、AOPP水平无明显相关性。单因素logistic回归分析显示，术后AOPP是老年患者LPN术后AKI发生的危险因素，但多因素logistic回归分析显示术后AOPP水平与老年患者LPN术后AKI的发生无明显相关性。提示老年患者LPN术中更需注重缩短肾动脉阻断时间和优化手术操作，减轻再灌注和手术损伤引起的氧化应激损伤，并关注围手术期肾功能的变化，及时进行干预治疗。
Nrf2是抗氧化基因的重要转录激活因子，在抗氧化保护中起重要作用，生理条件下，细胞质中的Nrf2与其抑制因子Kelch样ECH关联蛋白1(Kelch-like ECH-associated protein 1，Keap 1)结合，受Keap 1泛素化修饰，进而持续被蛋白酶系统降解。在中毒、高血糖和缺氧等导致氧化应激的因素诱导下，ROS可修饰Keap 1的半胱氨酸残基，削弱Keap 1对Nrf2的结合抑制作用，促进Nrf2与Keap 1解偶联后易位进入细胞核[9]，细胞核中Nrf2与小Maf等转录因子组成异二聚体，该异二聚体可识别并结合抗氧化反应原件，激活下游抗氧化蛋白的表达，包括谷氨酸-半胱氨酸连接酶亚单位(GCLC和GCLM)和谷胱甘肽-S-转移酶等[10]。GSH是细胞内最丰富、有效的ROS直接清除剂，可通过与氧化型GSH的转换来调节ROS水平，也是许多抗氧化酶的关键底物，通过作为多种抗氧化蛋白的辅助因子起到还原活性[11]。细胞内GSH水平降低可严重削弱细胞的抗氧化能力，而Nrf2可调控GSH合成限速酶(谷氨酸-半胱氨酸连接酶)、GSH结合反应关键酶(谷胱甘肽-S-转移酶)及谷胱甘肽过氧化物酶的表达，调节GSH的再生[21-23]。Guerrero-Hue等[24]研究表明，Nrf2缺失会加重机体氧化应激和炎症反应，导致不可逆和永久性的生物分子损伤，如DNA损伤、脂质过氧化或蛋白质变性，从而导致AKI的发生。Zhu等[12]发现，敲除Nrf2基因的小鼠肾组织切片中可检测到较高的ROS水平和更严重的肾小球损伤。Kim等[25]证实，老年鼠肾细胞核中Nrf2蛋白水平随着肾衰老而显著降低，并伴有肾小管间质纤维化、氧化应激和肾凋亡的增加。
侯静等[13]发现，GSH(600 mg/kg)治疗的I/R AKI模型大鼠SOD水平明显高于对照组，MDA、白细胞介素-6水平均明显低于对照组，并且治疗组尿素氮和SCr水平均有不同程度的降低。本研究发现，AKI组术前和术后的Nrf2水平明显低于非AKI组，分组分析显示，与术前相比，老年AKI亚组术后Nrf2、GSH水平均明显下降，而老年非AKI亚组、中年AKI亚组和中年非AKI亚组手术前后Nrf2、GSH水平无明显变化。Spearman相关分析显示，老年患者LPN术后AKI的发生与术后Nrf2、GSH水平的下降呈负相关，而中年患者LPN术后AKI的发生与围手术期Nrf2、GSH水平无明显相关性。单因素logistic回归分析显示，术后Nrf2、GSH是老年患者LPN术后AKI发生的保护因素；多因素logistic回归分析显示，术后GSH是老年患者LPN术后AKI发生的独立保护因素。提示以Nrf2/GSH为靶点的抗氧化剂治疗可能成为老年患者LPN术后AKI的新型预防策略。Han等[26]发现，益母草(7.5、15、30 mg/kg)对I/R大鼠模型预处理7 d可促进Nrf2核异位，上调血红素加氧酶-1等抗氧化剂水平，剂量依赖性地减轻肾炎症和氧化应激，并提高抗氧化活性，预防I/R相关AKI。Xu等[27]发现，枇杷苷(60、30、10 mg/kg)可通过上调人肾皮质近曲小管上皮细胞中Nrf2而降低核因子-κB的磷酸化，从而抑制炎症和氧化应激，并剂量依赖性地抑制氧糖剥夺/再灌注介导的细胞凋亡。目前尚无以Nrf2/GSH为靶点的抗氧化剂预防老年患者AKI的临床试验，未来可进一步探讨。
LPN术后AKI发生的危险因素一直是临床研究关注的重点，肥胖可加重机体氧化应激、内皮功能障碍和炎症反应[28]，增加eGFR、肾血流量和肾小管对钠的重吸收，促进肾小球高血压，还可促进高血压、动脉粥样硬化和II型糖尿病的进展，从而间接促进肾损伤；BMI相同但内脏脂肪过高的人患慢性肾病的风险更高[29]。本研究结果显示，AKI组BMI明显高于非AKI组，分组分析显示，老年AKI亚组的BMI明显高于老年非AKI亚组，而中年AKI亚组与中年非AKI亚组BMI没有明显差异，可能与老年人外周和皮下脂肪减少、内脏脂肪增加有关[30]；进一步分析证实，BMI是老年患者LPN术后AKI发生的独立危险因素，提示合并肥胖的老年患者LPN术后发生AKI的风险可能更高。
补液是预防低血容量和改善肾灌注的主要疗法，胶体中大分子在体内的停留时间较晶体长，扩容效果较晶体好，但有研究发现，羟乙基淀粉可能导致肾间质增生、巨噬细胞浸润和肾小管损伤，影响eGFR，从而引起肾损伤，且与低分子量羟乙基淀粉比较，高分子量羟乙基淀粉更容易引起肾损伤[31-32]。本研究发现，AKI组、老年AKI亚组和中年AKI亚组术中均明显输注了更多的羟乙基淀粉；进一步分析证实，术中胶体液入量是中年患者LPN术后AKI发生的独立危险因素，但不是老年患者LPN术后AKI发生的独立危险因素，该结果仍需扩大研究进一步验证。术中尿量可反映肾灌注情况来指导围手术期补液[33]，本研究发现，老年AKI亚组术中尿量明显少于老年非AKI亚组，中年AKI亚组明显少于中年非AKI亚组；进一步分析证实，术中尿量是老年和中年患者LPN术后AKI发生的保护因素，是中年患者LPN术后AKI发生的独立保护因素。因此，LPN术中补液应以晶体液为主，谨慎使用羟乙基淀粉，同时需密切观察术中尿量的变化。
有研究表明，肾体积与肾功能之间存在明显的相关性，保留肾实质体积的大小也是术后肾功能恢复的重要影响因素[34]。本研究中各组患者术前肿瘤大小并无差异，但老年AKI亚组术中切除肾体积和切除正常肾体积均明显大于老年非AKI亚组，中年AKI亚组明显大于中年非AKI亚组；进一步分析发现，手术切除肾体积是老年患者LPN术后AKI发生的独立危险因素，但不是中年患者LPN术后AKI发生的独立危险因素，提示老年患者LPN手术需更加注重肿瘤切除范围，在切除完整肿瘤的前提下尽量保留更多的肾单位。
本研究存在一定局限性：为单中心、小样本量研究，LPN术后AKI的影响因素较多，需要进一步大规模研究探讨各因素对AKI的影响；仅收集检测手术前后和术后24 h的指标，未评估长期肾功能的变化；对AKI的诊断依靠KDIGO指南诊断标准，无肾穿刺活检评估肾病理变化。
综上所述，本研究结果表明，老年患者LPN术后AKI的发生可能与术后AOPP水平升高和Nrf2、GSH水平降低有关，且术后GSH是老年患者LPN术后AKI发生的独立保护因素，而中年患者LPN术后AKI的发生则与围手术期MDA、AOPP、Nrf2、GSH水平变化无明显相关性。
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doi: 10.11855/j.issn.0577-7402.2255.2023.0604
  • 接收时间：2022-10-31
  • 首发时间：2025-11-21
  • 出版时间：2024-06-28
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  • 收稿日期：2022-10-31
  • 录用日期：2023-02-03
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    1山西医科大学麻醉学院，山西太原 030001
    2解放军总医院第三医学中心麻醉科，北京 100039

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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
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