中国临床药理学杂志

利拉鲁肽对急性肾损伤的作用及机制研究

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周璇 ^1a , 周晶晶 ^1a , 杜亚丽 ² , 林佩谕 ^1a , 王琪瑛 ^1b , 陈健 ³

中国临床药理学杂志 | 临床与基础桥接研究 2026,42(9): 1271-1276

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中国临床药理学杂志 |临床与基础桥接研究 2026 , 42 (9) : 1271 -1276

利拉鲁肽对急性肾损伤的作用及机制研究

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周璇^1a, 周晶晶^1a, 杜亚丽², 林佩谕^1a, 王琪瑛^1b, 陈健³

作者信息

^1a.温州医科大学附属第二医院，药学部，浙江温州 325000

^1b.温州医科大学附属第二医院，临床研究中心，浙江温州 325000

^2.浙江大学附属邵逸夫医院药学部，浙江绍兴 312300

^3.浙江省台州医院，浙江台州 317013

通讯作者:

陈健，副主任医师 MP: 13958585522 E-mail: chenjian@enzemed.com

作者简介:

周璇（1980-），女，副主任药师，主要从事医院药学、临床药学和临床药理方面的工作和研究

Research on the effects and mechanisms of liraglutide on acute kidney injury

Xuan ZHOU^1a, Jing-jing ZHOU^1a, Ya-li DU², Pei-yu LIN^1a, Qi-ying WANG^1b, Jian CHEN³

Affiliations

^1a.Department of Pharmacy, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China

^1b.Clinical Research Center, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China

^2.Department of Pharmacy, Sir Run Run Shaw Hospital Afflicated to School of Medicine of Zhejiang University, Shaoxing 312300, Zhejiang Province, China

^3.Taizhou Hospital of Zhejiang Province, Taizhou 317013, Zhejiang Province, China

出版时间: 2026-05-17 doi: 10.13699/j.cnki.1001-6821.2026.09.012

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摘要

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目的

探究利拉鲁肽对顺铂诱导的肾小管上皮（HK-2）细胞急性肾损伤的作用及相关机制。

方法

将HK-2细胞随机分为对照组、模型组和实验组。对照组常规培养，模型组用20 μmol·L^-1顺铂试剂处理48 h，实验组在模型组的基础上用100 nM利拉鲁肽试剂共同处理48 h。用细胞计数试剂盒-8（CCK-8）法检测细胞增殖活性，用蛋白质印迹法检测半胱氨酸天冬氨酸蛋白酶-3（Caspase 3）、活化的半胱氨酸天冬氨酸蛋白酶-3（C-Caspase3）、B细胞淋巴瘤-2（Bcl-2）相关X蛋白（BAX）、核因子E2相关因子2（Nrf-2）、超氧化物歧化酶2（SOD2）、血红素加氧酶1（HO-1）和内参β-actin蛋白相对表达水平，用实时荧光定量聚合酶链反应法检测肾损伤分子-1（Kim-1）、Bcl-2和BAX相关信使核糖核酸（mRNA）相对表达水平，用原位末端标记法（TUNEL）检测细胞凋亡情况，用超氧化物阴离子荧光探针（DHE）法检测活性氧（ROS）水平。

结果

CCK-8法检测得出，100 nmol·L^-1作为利拉鲁肽最佳干预浓度。干预48 h后，对照组、模型组和实验组的K1M-1 mRNA相对表达水平分别为0.98±0.25、56.23±23.25和2.61±0.79；BAX/Bcl-2 mRNA相对表达水平分别为1.01±0.08、15.47±3.01和5.41±0.54；细胞凋亡率分别为（5.60±0.40）%、（40.00±4.79）%和（6.40±0.87）%；DHE阳性率荧光值分别为1.95±0.03、3.01±0.28和1.51±0.13；Nrf-2蛋白相对表达水平分别为0.80±0.01、0.47±0.01和0.68±0.02；SOD2蛋白相对表达水平分别为0.96±0.04、0.57±0.28和0.91±0.04；HO-1蛋白相对表达水平分别为1.01±0.08、0.47±0.05和1.56±0.18。模型组与对照组比较、实验组与模型组比较，上述指标在统计学上差异均有统计学意义（P<0.05，P<0.01，P<0.001，P<0.000 1）。

结论

利拉鲁肽可以降低顺铂诱导的急性肾损伤肾小管上皮细胞凋亡率与氧化应激水平，并提高超氧化物水平。

关键词

利拉鲁肽 / 顺铂 / 急性肾损伤 / 肾小管上皮细胞 / 氧化应激

Abstract

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Objective

To investigate the effect and mechanism of liraglutide on cisplatin-induced acute kidney injury in renal tubular epithelial (HK-2) cells.

Methods

HK-2 cells were randomly divided into control group, model group and experimental group. The control group was cultured conventionally, the model group was treated with 20 μmol·L^-1 cisplatin reagent for 48 hours, and the experimental group was treated with 100 nM liraglutide reagent in addition to the model group for 48 hours. Cell proliferation activity was detected by cell counting kit-8 (CCK-8) method. Western blot was used to detect cysteine-aspartic acid protease 3 (Caspase 3), cleaved cysteine-aspartic acid protease 3(C-Caspase3), B cell lymphoma-2 (Bcl-2) associated X protein (BAX), nuclear factor E2 related factor 2 (Nrf-2), superoxide dismutase 2 (SOD2), heme oxygenase-1 (HO-1) and reference β-actin protein relative expression levels; the relative expression levels of kidney injury molecule-1 (Kim-1), BAX and Bcl-2 related messenger ribonucleic acid (mRNA) were detected by real-time fluorescent quantitative polymerase chain reaction, and cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dutP nick end labeling (TUNEL). Reactive oxygen species (ROS) levels were measured by superoxide anion fluorescent probe (DHE).

Results

CCK-8 assay showed that 100 nmol·L^-1 was the optimal intervention concentration of liraglutide. After 48 hours of intervention, the relative expression levels of K1M-1 mRNA in control group, model group and experimental group were 0.98±0.25, 56.23±23.25 and 2.61±0.79, respectively; BAX /Bcl-2 mRNA relative expression levels were 1.01±0.08, 15.47±3.01 and 5.41±0.54, respectively; the apoptosis rates were (5.60±0.40)%, (40.00±4.79)% and (6.40±0.87)%, respectively; the fluores cence value of positive rates of DHE were 1.95±0.03, 3.01±0.28 and 1.51±0.13, respectively; the relative expression levels of Nrf-2 protein were 0.80±0.01, 0.47±0.01 and 0.68±0.02, respectively; the relative expression levels of SOD2 protein were 0.96±0.04, 0.57±0.28 and 0.91±0.04, respectively; the relative expression levels of HO-1 were 1.01±0.08, 0.47±0.05 and 1.56±0.18, respectively. There were statistically significant differences in the above indicators between model group and control group, and between experimental group and model group (P<0.05, P<0.01, P<0.001, P<0.000 1).

Conclusion

Liraglutide can reduce the apoptosis rate and oxidative stress level of renal tubular epithelial cells in cisplatin-induced acute kidney injury, and increase the level of superoxide.

Key words

liraglutide / cisplatin / acute kidney injury / renal tubular epithelial cell / oxidative stress

引用本文

周璇, 周晶晶, 杜亚丽, 林佩谕, 王琪瑛, 陈健. 利拉鲁肽对急性肾损伤的作用及机制研究. 中国临床药理学杂志, 2026 , 42 (9) : 1271 -1276 . DOI: 10.13699/j.cnki.1001-6821.2026.09.012

Xuan ZHOU, Jing-jing ZHOU, Ya-li DU, Pei-yu LIN, Qi-ying WANG, Jian CHEN. Research on the effects and mechanisms of liraglutide on acute kidney injury[J]. Chinese Journal of Clinical Pharmacology, 2026 , 42 (9) : 1271 -1276 . DOI: 10.13699/j.cnki.1001-6821.2026.09.012

基金

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温州市科技局基金支持项目(Y20220897)

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2026年第42卷第9期

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文章信息

doi: 10.13699/j.cnki.1001-6821.2026.09.012

接收时间：2025-09-13
首发时间：2026-08-06
出版时间：2026-05-17

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收稿日期：2025-09-13

基金

温州市科技局基金支持项目(Y20220897)

作者信息

^1a.温州医科大学附属第二医院，药学部，浙江温州 325000

^1b.温州医科大学附属第二医院，临床研究中心，浙江温州 325000

^2.浙江大学附属邵逸夫医院药学部，浙江绍兴 312300

^3.浙江省台州医院，浙江台州 317013

通讯作者:

陈健，副主任医师 MP: 13958585522 E-mail: chenjian@enzemed.com

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https://castjournals.cast.org.cn/joweb/zglcylxzz/CN/10.13699/j.cnki.1001-6821.2026.09.012

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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