Article(id=1151437195169640745, tenantId=1146029695717560320, journalId=1149652044408987649, issueId=1151437189243089177, articleNumber=null, orderNo=null, doi=10.19812/j.cnki.jfsq11-5956/ts.20240926003, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1727280000000, receivedDateStr=2024-09-26, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1752453619996, onlineDateStr=2025-07-14, pubDate=1749916800000, pubDateStr=2025-06-15, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1752453619996, onlineIssueDateStr=2025-07-14, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1752453619996, creator=13701087609, updateTime=1752453619996, updator=13701087609, issue=Issue{id=1151437189243089177, tenantId=1146029695717560320, journalId=1149652044408987649, year='2025', volume='16', issue='11', pageStart='1', pageEnd='320', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1752453618584, creator=13701087609, updateTime=1767768054466, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1215670588966883492, tenantId=1146029695717560320, journalId=1149652044408987649, issueId=1151437189243089177, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1215670588966883493, tenantId=1146029695717560320, journalId=1149652044408987649, issueId=1151437189243089177, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=222, endPage=227, ext={EN=ArticleExt(id=1151895326035636827, articleId=1151437195169640745, tenantId=1146029695717560320, journalId=1149652044408987649, language=EN, title=Protective effect of β-nicotinamide mononucleotide on the liver of hyperlipidemic rats, columnId=1151895321388347923, journalTitle=Journal of Food Safety & Quality, columnName=Food Analysis and Detection, runingTitle=null, highlight=null, articleAbstract=

Objective To investigate the lipid-lowering and liver protective effects of β-nicotinamide mononucleotide (NMN) on hyperlipidemic model rats. Methods The 50 male SD rats were randomly divided into a normal group, a model group and low, medium and high dose groups of NMN (10, 50, 250 mg/kg), with 10 rats in each group. The normal group was given maintenance feed, while the other groups were given high-fat feed to establish a high-fat model. After successful modeling, gastric lavage intervention was performed in each group. After 5 weeks of intervention, serum biochemical indicators and blood lipids were measured, including total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-c), high densitylipoprotein cholesterol (HDL-c) levels, glucose (GLU), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CREA) levels, combined with pathological observation of liver histological changes and nonalcoholic fattyliver disease activity score (NAS) of liver tissues was evaluated. Results Compared with the normal group, the body weight of the model group rats increased significantly, and the levels of TG, TC, LDL-c and ALT (P<0.01) in their serum increased significantly, AST and ALP levels significantly increased (P<0.05) The level of HDL-c (P<0.05) decreased significantly, while GLU and CREA showed no significant changes. Compared with the model group, the TG, TC and ALT levels in the low and medium dose groups were significantly reduced (P<0.05), the LDL-c in the medium dose group was significantly reduced (P<0.01). The TG, AST and ALT content in the high-dose group was significantly reduced (P<0.05). However, TC and LDL-c were significantly reduced (P<0.01); there was no significant difference in HDL-c, ALP, GLU and CREA. Compared with the model group, the low, medium, and high dose groups improved hepatic steatosis and inflammatory infiltration in rats, and the total score of NAS in the medium and high dose groups was reduced and showed statistical significance. Conclusion NMN can reduce the blood lipid levels in hyperlipidemic SD rats and has a certain protective effect on the liver.

, correspAuthors=Tong-Jin YANG, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, authorCompany=null, fund=null, authors=null, authorsList=Xiao-Han JIANG, Ning-Juan LIANG, Rui LI, Yan WANG, Tong-Jin YANG), CN=ArticleExt(id=1151895330808754915, articleId=1151437195169640745, tenantId=1146029695717560320, journalId=1149652044408987649, language=CN, title=β-烟酰胺单核苷酸对高脂血症大鼠肝脏的保护作用研究, columnId=1151895321958773274, journalTitle=食品安全质量检测学报, columnName=食品分析与检测, runingTitle=null, highlight=null, articleAbstract=

目的 探究β-烟酰胺单核苷酸(nicotinamide mononucleotide, NMN)对高脂血症模型大鼠的降脂和对肝脏的保护作用。方法 50只雄性SD大鼠, 随机分为正常组、模型组和NMN低、中、高剂量组(10、50、250 mg/kg), 每组10只, 正常组给予维持饲料, 其余各组给予高脂饲料建立高脂模型, 造模成功后分别进行灌胃干预。干预5周后, 检测血清中总胆固醇(total cholesterol, TC)、甘油三酯(triglyceride,TG)、低密度脂蛋白(low density lipoprotein cholesterol, LDL-c)及高密度脂蛋白(high densitylipoprotein cholesterol, HDL-c)、血糖(glucose, GLU)、碱性磷酸酶(alkaline phosphatase, ALP)、丙氨酸氨基转移酶(alanine aminotransferase, ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase, AST)、肌酐(creatinine, CREA)水平, 并结合病理观察肝脏组织学变化和进行非酒精性脂肪肝活动度评分(nonalcoholic fattyliver disease activity score, NAS)评分。结果 与正常组相比, 模型组大鼠体重增加明显, 其血清中的TG、TC、LDL-c和ALT含量极显著上升(P<0.01), AST和ALP含量显著上升(P<0.05), HDL-c含量显著降低(P<0.05), GLU和CREA无显著变化。与模型组相比, 低中剂量组TG、TC、ALT显著降低(P<0.05), 中剂量组LDL-c极显著降低(P<0.01); 高剂量组TG、AST和ALT含量显著降低(P<0.05)而TC和LDL-c极显著降低(P<0.01); HDL-c、ALP、GLU和CREA无显著差异。与模型组相比, 低中高剂量组对大鼠的肝细胞脂肪变性, 炎症浸润均有改善, 中高剂量组的NAS总分降低且有统计学意义。结论 NMN能降低高脂血症SD大鼠的血脂水平, 并对肝脏有一定的保护作用。

, correspAuthors=杨同金, authorNote=null, correspAuthorsNote=
* 杨同金(1982—), 男, 硕士, 副主任技师, 主要研究方向为毒性病理学。E-mail:
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蒋小涵(1991—), 女, 硕士, 主管技师, 主要研究方向为毒性病理学。E-mail:

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Archives of Pharmacal Research, 2018, 41(12): 1190-1198., articleTitle=Flavonoids extracted from Linaria vulgaris protect against hyperlipidemia and hepatic steatosis induced by western-type diet in mice, refAbstract=null)], funds=[Fund(id=1167033391137436628, tenantId=1146029695717560320, journalId=1149652044408987649, articleId=1151437195169640745, awardId=AHWJ2023A30153, language=CN, fundingSource=安徽省卫生健康委科研项目(AHWJ2023A30153), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1167033388646020004, tenantId=1146029695717560320, journalId=1149652044408987649, articleId=1151437195169640745, xref=null, ext=[AuthorCompanyExt(id=1167033388650214309, tenantId=1146029695717560320, journalId=1149652044408987649, articleId=1151437195169640745, companyId=1167033388646020004, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Anhui Provincial Center for Disease Control and Prevention, Hefei 230601, China), AuthorCompanyExt(id=1167033388658602918, tenantId=1146029695717560320, journalId=1149652044408987649, articleId=1151437195169640745, companyId=1167033388646020004, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=安徽省疾病预防控制中心, 合肥 230601)])], figs=[ArticleFig(id=1167033390227272648, tenantId=1146029695717560320, journalId=1149652044408987649, articleId=1151437195169640745, language=EN, label=Fig.1, caption=HE-stained pathological sections of liver tissuesfrom SD rats after drug administration (×200), figureFileSmall=ESTS7Vi7ZnpaJsP00SVhww==, figureFileBig=CPTbvEWFAc4xvAO+RE99EQ==, tableContent=null), ArticleFig(id=1167033390294381513, tenantId=1146029695717560320, journalId=1149652044408987649, articleId=1151437195169640745, language=CN, label=图1, caption=干预后高脂血症SD大鼠肝组织HE病理切片图(×200)

注: A. 正常组; B. 模型组; C. NMN-L组; D. NMN-M组; E. NMN-H组。

, figureFileSmall=ESTS7Vi7ZnpaJsP00SVhww==, figureFileBig=CPTbvEWFAc4xvAO+RE99EQ==, tableContent=null), ArticleFig(id=1167033390340518858, tenantId=1146029695717560320, journalId=1149652044408987649, articleId=1151437195169640745, language=EN, label=Table 1, caption=

Comparison of blood lipids in model group and normal group after 2 weeks of modeling (mmol/L)

, figureFileSmall=null, figureFileBig=null, tableContent=
组别 个数 TG TC HDL-c LDL-c
正常组 10 1.80±1.37 1.37±0.49 0.78±0.14 0.32±0.26
模型组 40 3.04±1.24** 2.24±0.42** 0.73±0.13 0.81±0.20**
), ArticleFig(id=1167033390407627723, tenantId=1146029695717560320, journalId=1149652044408987649, articleId=1151437195169640745, language=CN, label=表1, caption=

造模2周后模型组与正常组血脂的比较(mmol/L)

, figureFileSmall=null, figureFileBig=null, tableContent=
组别 个数 TG TC HDL-c LDL-c
正常组 10 1.80±1.37 1.37±0.49 0.78±0.14 0.32±0.26
模型组 40 3.04±1.24** 2.24±0.42** 0.73±0.13 0.81±0.20**
), ArticleFig(id=1167033390453765068, tenantId=1146029695717560320, journalId=1149652044408987649, articleId=1151437195169640745, language=EN, label=Table 2, caption=

Effects of NMN on weight of SD rats with hyperlipidemia (n=8)

, figureFileSmall=null, figureFileBig=null, tableContent=
组别 干预第1周 干预第2周 干预第3周 干预第4周 干预第5周
正常组 353.00±41.61 394.89±34.28 450.22±35.48 441.22±35.25 486.14±40.35
模型组 384.40±18.56* 426.25±27.87* 492.38±34.57* 523.38±29.19* 545.00±33.59*
NMN-L 376.17±27.07 414.00±34.00 483.44±40.88* 498.78±40.25 519.56±40.44
NMN-M 365.25±26.75 412.38±30.80 466.50±33.30 484.88±38.77# 506.75±40.21#
NMN-H 368.65±19.45 411.25±23.63 463.50±26.60 486.88±30.15# 507.13±27.85#
), ArticleFig(id=1167033390516679629, tenantId=1146029695717560320, journalId=1149652044408987649, articleId=1151437195169640745, language=CN, label=表2, caption=

NMN对高脂血症SD大鼠体重的影响(n=8)

, figureFileSmall=null, figureFileBig=null, tableContent=
组别 干预第1周 干预第2周 干预第3周 干预第4周 干预第5周
正常组 353.00±41.61 394.89±34.28 450.22±35.48 441.22±35.25 486.14±40.35
模型组 384.40±18.56* 426.25±27.87* 492.38±34.57* 523.38±29.19* 545.00±33.59*
NMN-L 376.17±27.07 414.00±34.00 483.44±40.88* 498.78±40.25 519.56±40.44
NMN-M 365.25±26.75 412.38±30.80 466.50±33.30 484.88±38.77# 506.75±40.21#
NMN-H 368.65±19.45 411.25±23.63 463.50±26.60 486.88±30.15# 507.13±27.85#
), ArticleFig(id=1167033390579594190, tenantId=1146029695717560320, journalId=1149652044408987649, articleId=1151437195169640745, language=EN, label=Table 3, caption=

Effects of NMN on blood lipids and blood glucose of SD rats with hyperlipidemia (mmol/L, n=8)

, figureFileSmall=null, figureFileBig=null, tableContent=
组别 TG TC HDL-c LDL-c GLU
正常组 0.69±0.15 1.28±0.20 0.78±1.59 0.50±0.50 8.59±1.23
模型组 1.18±0.14** 1.98±0.19** 0.69±0.12* 1.25±0.12** 9.40±0.99
NMN-L 0.91±0.25# 1.75±1.27# 0.65±0.08 1.15±0.17 9.94±0.59
NMN-M 0.89±0.20# 1.73±1.49# 0.61±0.05 1.11±0.11# 8.61±1.26
NMN-H 0.86±0.16# 1.61±1.98## 0.67±0.08 0.97±0.08## 9.29±0.56
), ArticleFig(id=1167033390650897359, tenantId=1146029695717560320, journalId=1149652044408987649, articleId=1151437195169640745, language=CN, label=表3, caption=

NMN对高脂血症SD大鼠血脂和血糖的影响(mmol/L, n=8)

, figureFileSmall=null, figureFileBig=null, tableContent=
组别 TG TC HDL-c LDL-c GLU
正常组 0.69±0.15 1.28±0.20 0.78±1.59 0.50±0.50 8.59±1.23
模型组 1.18±0.14** 1.98±0.19** 0.69±0.12* 1.25±0.12** 9.40±0.99
NMN-L 0.91±0.25# 1.75±1.27# 0.65±0.08 1.15±0.17 9.94±0.59
NMN-M 0.89±0.20# 1.73±1.49# 0.61±0.05 1.11±0.11# 8.61±1.26
NMN-H 0.86±0.16# 1.61±1.98## 0.67±0.08 0.97±0.08## 9.29±0.56
), ArticleFig(id=1167033390713811920, tenantId=1146029695717560320, journalId=1149652044408987649, articleId=1151437195169640745, language=EN, label=Table 4, caption=

Effects of NMN on liver and renal function of SD rats with hyperlipidemia (mmol/L, n=8)

, figureFileSmall=null, figureFileBig=null, tableContent=
组别 ALT AST ALP CREA
正常组 32.74±4.02 89.83±12.60 173.29±35.31 28.33±3.49
模型组 70.26±44.27** 163.88±112.70* 254.57±38.92* 28.31±1.26
NMN-L 44.87±14.51# 142.08±53.06 240.86±79.73 30.04±3.96
NMN-M 44.37±4.63# 131.21±20.31 224.86±30.34 27.60±2.68
NMN-H 43.14±8.12# 105.10±8.99# 219.57±54.27 28.63±4.87
), ArticleFig(id=1167033390772532177, tenantId=1146029695717560320, journalId=1149652044408987649, articleId=1151437195169640745, language=CN, label=表4, caption=

NMN对高脂血症SD大鼠肝肾功能的影响(mmol/L, n=8)

, figureFileSmall=null, figureFileBig=null, tableContent=
组别 ALT AST ALP CREA
正常组 32.74±4.02 89.83±12.60 173.29±35.31 28.33±3.49
模型组 70.26±44.27** 163.88±112.70* 254.57±38.92* 28.31±1.26
NMN-L 44.87±14.51# 142.08±53.06 240.86±79.73 30.04±3.96
NMN-M 44.37±4.63# 131.21±20.31 224.86±30.34 27.60±2.68
NMN-H 43.14±8.12# 105.10±8.99# 219.57±54.27 28.63±4.87
), ArticleFig(id=1167033390835446738, tenantId=1146029695717560320, journalId=1149652044408987649, articleId=1151437195169640745, language=EN, label=Table 5, caption=

Effects of NMN on NAS score of liver tissue in SD rats with hyperlipidemia (n=8)

, figureFileSmall=null, figureFileBig=null, tableContent=
组别 脂肪变性 小叶炎症 气球样变 NAS总分
正常组 0.25±0.46 0.25±0.46 0±0 0.50±0.76
模型组 2.63±0.52** 1.88±0.83** 0±0 4.50±1.20**
NMN-L 2.50±0.53** 1.25±0.71* 0±0 3.75±0.71**
NMN-M 1.75±0.46**# 1.38±0.92* 0±0 3.13±1.25**#
NMN-H 1.13±0.64*## 0.50±0.53# 0±0 1.63±0.92*##
), ArticleFig(id=1167033391003218899, tenantId=1146029695717560320, journalId=1149652044408987649, articleId=1151437195169640745, language=CN, label=表5, caption=

NMN对高脂血症SD大鼠肝组织NAS评分的影响(n=8)

, figureFileSmall=null, figureFileBig=null, tableContent=
组别 脂肪变性 小叶炎症 气球样变 NAS总分
正常组 0.25±0.46 0.25±0.46 0±0 0.50±0.76
模型组 2.63±0.52** 1.88±0.83** 0±0 4.50±1.20**
NMN-L 2.50±0.53** 1.25±0.71* 0±0 3.75±0.71**
NMN-M 1.75±0.46**# 1.38±0.92* 0±0 3.13±1.25**#
NMN-H 1.13±0.64*## 0.50±0.53# 0±0 1.63±0.92*##
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β-烟酰胺单核苷酸对高脂血症大鼠肝脏的保护作用研究
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蒋小涵 , 梁宁娟 , 李锐 , 王岩 , 杨同金 *
食品安全质量检测学报 | 食品分析与检测 2025,16(11): 222-227
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食品安全质量检测学报 | 食品分析与检测 2025, 16(11): 222-227
β-烟酰胺单核苷酸对高脂血症大鼠肝脏的保护作用研究
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蒋小涵 , 梁宁娟, 李锐, 王岩, 杨同金*
作者信息
  • 安徽省疾病预防控制中心, 合肥 230601
  • 蒋小涵(1991—), 女, 硕士, 主管技师, 主要研究方向为毒性病理学。E-mail:

通讯作者:

* 杨同金(1982—), 男, 硕士, 副主任技师, 主要研究方向为毒性病理学。E-mail:
Protective effect of β-nicotinamide mononucleotide on the liver of hyperlipidemic rats
Xiao-Han JIANG , Ning-Juan LIANG, Rui LI, Yan WANG, Tong-Jin YANG*
Affiliations
  • Anhui Provincial Center for Disease Control and Prevention, Hefei 230601, China
出版时间: 2025-06-15 doi: 10.19812/j.cnki.jfsq11-5956/ts.20240926003
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目的 探究β-烟酰胺单核苷酸(nicotinamide mononucleotide, NMN)对高脂血症模型大鼠的降脂和对肝脏的保护作用。方法 50只雄性SD大鼠, 随机分为正常组、模型组和NMN低、中、高剂量组(10、50、250 mg/kg), 每组10只, 正常组给予维持饲料, 其余各组给予高脂饲料建立高脂模型, 造模成功后分别进行灌胃干预。干预5周后, 检测血清中总胆固醇(total cholesterol, TC)、甘油三酯(triglyceride,TG)、低密度脂蛋白(low density lipoprotein cholesterol, LDL-c)及高密度脂蛋白(high densitylipoprotein cholesterol, HDL-c)、血糖(glucose, GLU)、碱性磷酸酶(alkaline phosphatase, ALP)、丙氨酸氨基转移酶(alanine aminotransferase, ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase, AST)、肌酐(creatinine, CREA)水平, 并结合病理观察肝脏组织学变化和进行非酒精性脂肪肝活动度评分(nonalcoholic fattyliver disease activity score, NAS)评分。结果 与正常组相比, 模型组大鼠体重增加明显, 其血清中的TG、TC、LDL-c和ALT含量极显著上升(P<0.01), AST和ALP含量显著上升(P<0.05), HDL-c含量显著降低(P<0.05), GLU和CREA无显著变化。与模型组相比, 低中剂量组TG、TC、ALT显著降低(P<0.05), 中剂量组LDL-c极显著降低(P<0.01); 高剂量组TG、AST和ALT含量显著降低(P<0.05)而TC和LDL-c极显著降低(P<0.01); HDL-c、ALP、GLU和CREA无显著差异。与模型组相比, 低中高剂量组对大鼠的肝细胞脂肪变性, 炎症浸润均有改善, 中高剂量组的NAS总分降低且有统计学意义。结论 NMN能降低高脂血症SD大鼠的血脂水平, 并对肝脏有一定的保护作用。

β-烟酰胺单核苷酸  /  高脂血症模型  /  降血脂  /  护肝

Objective To investigate the lipid-lowering and liver protective effects of β-nicotinamide mononucleotide (NMN) on hyperlipidemic model rats. Methods The 50 male SD rats were randomly divided into a normal group, a model group and low, medium and high dose groups of NMN (10, 50, 250 mg/kg), with 10 rats in each group. The normal group was given maintenance feed, while the other groups were given high-fat feed to establish a high-fat model. After successful modeling, gastric lavage intervention was performed in each group. After 5 weeks of intervention, serum biochemical indicators and blood lipids were measured, including total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-c), high densitylipoprotein cholesterol (HDL-c) levels, glucose (GLU), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CREA) levels, combined with pathological observation of liver histological changes and nonalcoholic fattyliver disease activity score (NAS) of liver tissues was evaluated. Results Compared with the normal group, the body weight of the model group rats increased significantly, and the levels of TG, TC, LDL-c and ALT (P<0.01) in their serum increased significantly, AST and ALP levels significantly increased (P<0.05) The level of HDL-c (P<0.05) decreased significantly, while GLU and CREA showed no significant changes. Compared with the model group, the TG, TC and ALT levels in the low and medium dose groups were significantly reduced (P<0.05), the LDL-c in the medium dose group was significantly reduced (P<0.01). The TG, AST and ALT content in the high-dose group was significantly reduced (P<0.05). However, TC and LDL-c were significantly reduced (P<0.01); there was no significant difference in HDL-c, ALP, GLU and CREA. Compared with the model group, the low, medium, and high dose groups improved hepatic steatosis and inflammatory infiltration in rats, and the total score of NAS in the medium and high dose groups was reduced and showed statistical significance. Conclusion NMN can reduce the blood lipid levels in hyperlipidemic SD rats and has a certain protective effect on the liver.

β-nicotinamide mononucleotide  /  hyperlipidemia model  /  lipid-lowering  /  liver protection
蒋小涵, 梁宁娟, 李锐, 王岩, 杨同金. β-烟酰胺单核苷酸对高脂血症大鼠肝脏的保护作用研究. 食品安全质量检测学报, 2025 , 16 (11) : 222 -227 . DOI: 10.19812/j.cnki.jfsq11-5956/ts.20240926003
Xiao-Han JIANG, Ning-Juan LIANG, Rui LI, Yan WANG, Tong-Jin YANG. Protective effect of β-nicotinamide mononucleotide on the liver of hyperlipidemic rats[J]. Journal of Food Safety & Quality, 2025 , 16 (11) : 222 -227 . DOI: 10.19812/j.cnki.jfsq11-5956/ts.20240926003
高脂血症是一种由于脂质代谢异常导致血液中甘油三酯、总胆固醇和低密度脂蛋白中的一种或多种超过正常范围水平的病症[1-3]。与肥胖症之间存在紧密联系, 可导致高血压、冠心病和糖尿病等一系列慢性疾病, 给人类和社会造成重大影响[4]。因此, 采取必要的手段治疗或者减轻高脂血症的影响, 对人类健康具有重要价值。
β-烟酰胺单核苷酸(nicotinamide mononucleotide, NMN)是一种具有重要生物学活性的核苷酸, 是NAD+(辅酶I)和NADP+(辅酶II)的重要前体物之一[5-6]。这两种酶广泛参与体内许多重要的生化反应都与其有关, 包括DNA修复, 细胞调亡, 细胞衰老和细胞内能量代谢等[7-10]。NMN主要存在于西兰花、卷心菜和虾等天然食物中, 但含量稀少, 因此在一些国家将作其为食品原料和膳食补充剂原料成分使用。目前在中国市场上, NMN是通过跨境电商的方式使众多添加NMN的产品进入国内市场, 同时, 本研究也有大量厂家在生产研发以NMN为主要原料的食品和保健品。在2022年8月12日, 《β-烟酰胺单核苷酸产品要求和测试方法》(T/FDSA 029-2022)团体标准正式实施, 这也为NMN产品的生产和质量控制提供了规范[11]。目前, 相关研究表明NMN的补充剂可以降低血压并改善血管内皮的炎症反应[12], 补充NMN可预防小鼠切除卵巢后骨质疏松症的发生并能增强骨折后愈合能力[13]。为探究NMN更多的作用价值, 根据团队前期研究其急性经口毒性试验半数致死剂量(median lethal dose, LD50)>5000 mg/kg[14], 本研究将NMN作为受试物, 分低、中、高3个剂量组对高脂血症SD大鼠灌胃, 评价其降脂效果并观察对肝脏保护作用, 为后期NMN研究研发提供科学依据。
选用SPF级雄性SD大鼠[(体重200 g±20 g), 生产许可证号: SCXK(浙)2019-0004], 购于杭州子源实验动物科技有限公司; 饲养的温度保持在22~26 ℃, 湿度维持在40%~50%, 实验动物使用许可证号: SYXK(皖)2019-011。动物实验经安徽省疾病预防控制中心实验动物福利伦理委员会批准, 编号: 2024003。
NMN(白色粉末, 纯度99.9%, 中航新材料有限公司), 高脂饲料(组成: 20%蔗糖、15%猪油、1.2%胆固醇、0.2%胆酸钠)(江苏省协同医药生物公司); 总胆固醇(total cholesterol, TC)、甘油三酯(triglyceride, TG)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol, LDL-c)、高密度脂蛋白胆固醇(high densitylipoprotein cholesterol, HDL-c)、葡萄糖(glucose, GLU)、丙氨酸氨基转移酶(alanine aminotransferase, ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase, AST)、碱性磷酸酶(alkaline phosphatase, ALP)、肌酐(creatinine, CREA)(中国贝克曼库尔特公司); 苏木精伊红染色液(珠海贝索生物公司)。
AU480全自动生物化学分析仪(中国贝克曼库尔特公司); RM2126RT徕卡石蜡病理切片机(上海徕卡公司); HP300全自动病理组织脱水机、DP360+CS500病理染封一体机(中国达科为医疗科技公司); OlympusBX51显微镜(日本奥林巴斯公司); L4-5K医用离心机(湖南可成仪器设备公司); JA1203电子天平(精度0.001 g, 上海精科仪器公司)。
参考《保健食品功能检验与评价方法(2023年版)》中的方法进行动物实验。实验大鼠适应性饲养一周, 然后按体重随机分为2组, 10只大鼠给予维持饲料作为正常组, 40只大鼠给予高脂饲料作为模型组。每周称重一次, 2周后, 不禁食, 心脏采血并分离血清, 测定血清TC、TG、LDL-c、HDL-c水平。各组与正常组比较, TC、TG、LDL-c升高差异均有显著性, 判定模型成立。
筛选成模大鼠40只, 随机分为4组; 模型组, NMN低剂量组(NMN-L), NMN中剂量组(NMN-M), NMN高剂量组(NMN-H), 药物剂量: 10、50、250 mg/kg(根据人体推荐摄入量的1倍、5倍、25倍来设置)。每组10只, 以1 mL/100 g每日灌胃给予受试物; 正常组和模型组给予等体积的纯水, 每日定时灌胃, 连续干预5周后, 处死进行取材。灌胃期间除正常对照组继续维持饲料喂养, 其余各组高脂饲料喂养。
每日观察大鼠毛色, 状态, 每周测量大鼠体重, 并记录。
干预期结束后乙醚麻醉, 腹主动脉采集血样。分离血清, 检测血液生化指标, 血脂(TG、TC、HDL-c、LDL-c); 血糖(GLU); 肝肾功能(ALT、AST、ALP、CREA)。
取部分肝脏于4%的多聚甲醛中固定, 脱水, 石蜡包埋, 连续切片(5 μm), 苏木精-伊红(hematoxylin-eosin, HE)染色, 中性树胶封片, OlympusBX51显微镜观察肝脏组织病变情况并采集照片。
评估肝脏病变程度是通过非酒精性脂肪肝活动度评分(nonalcoholic fattyliver disease activity score, NAS): (1)肝细胞脂肪变(低倍镜下)<5%为0分, 5%~33%为1分, 34%~66%为2分, >66%为3分; (2)肝小叶内未见炎症病灶(20倍视野)为0分, <2个炎症病灶为1分, 2~4个炎症病灶为2分, >4个炎症病灶为3分; (3)肝细胞未见气球样变为0分, 气球样变少见为1分, 气球样变多见为2分; 3个方面的积分之和即为NAS总分[15]
采用SPSS 27.0对实验数据进行统计分析, 计量资料数据用平均数±标准偏差表示。两组间比较采用两独立样本均数t检验; 多组间比较采用单因素方差分析进行检验, 若方差齐, 采用最小显著差法(least significant difference, LSD); 若方差不齐, 采用Dunnett-t3。检验以P<0.05认为差异有统计学意义。
2周后乙醚麻醉, 心脏采血检测血脂4项。由表1可知, 与正常组对比, 模型组的TG、TC和LDL-c均显著高于正常组(P<0.01), 可认为高脂血症SD大鼠造模成功, 且为混合型高脂血症动物模型。可进行下一步干预实验。
高脂血脂SD大鼠体重呈不同的变化结果如表2所示。在实验初期, 各组大鼠体重差异不显著。实验过程中正常组大鼠的体重增长趋势较为平缓, 而模型组的体重增长迅速, 且与正常组相比, 具有显著性(P<0.05)。NMN各剂量组可以减缓其体重增速, 其中NMN-M和NMN-H组体重增长趋势大致相同, 但NMN干预4周后, NMN-M和NMN-H组体重均显著低于模型组(P<0.05)。
表3所示, 与正常组对比, 模型组大鼠血清中TG、TC和LDL-c含量极显著上升(P<0.01); HDL-c的水平显著降低(P<0.05); 血糖虽有上升, 但不显著。与模型组对比, NMN各剂量组血清中的TG、TC含量显著降低(P<0.05或P<0.01), 其中NMN-H组降脂效果最明显, HDL-c和血糖的含量变化无显著性变化。
表4所示, 与正常组对比, 模型组大鼠血清中的ALT、AST和ALP含量显著上升(P<0.05或P<0.01), 但CREA无显著性变化; 与模型组对比, NMN各剂量组血清中的ALT含量显著降低(P<0.05), 而NMN-L和NMN-M组血清中的AST虽有下降, 但不显著, NMN-H组显著性下降(P<0.05); ALP和CREA无显著性变化。
图1所示, 正常组肝细胞肝小叶结构清楚, 肝窦清晰可见, 呈放射状排列, 几乎未见肝细胞脂肪变性、坏死等改变。模型组肝细胞内脂肪明显可见, 肝组织结构异常, 细胞内有大量小脂质空泡伴有肿胀现象, 呈“泡沫”样外观。与模型组对比, NMN干预后, 各组的大鼠肝细胞损伤有不同程度的改善, 肝细胞脂肪蓄积减少, 细胞肿胀也改善且呈剂量依赖性改变。
表5所示, 与正常组相比, 模型组和各剂量组的脂肪变性, 小叶炎症的评分均显著增高(P<0.05或P<0.01), 除NMN-H组的小叶炎症评分, 都未见明显的气球样变。与模型组相比, NMN-H组的脂肪变性的评分和NMN-H组的小叶炎症评分显著降低(P<0.05或P<0.01)。计算NAS总分, 正常组最低, 模型组最高, 各剂量组介于两者之间。与模型组相比, NMN-M和NMN-H组的NAS总分显著降低(P<0.05或P<0.01)。
随着人们生活方式和饮食结构的改变, 血脂异常逐年增多, 脂肪肝、冠心病和脑卒中等疾病都与其有关, 已成为威胁我国居民健康重要因素[16-17]。目前, 临床上常用他汀[18]、贝特类[19]或二者联用治疗高脂血症[20], 但会引发肌肉毒性和肝毒性等相关性不良反应, 且停药后易导致血脂反弹[21-22]。因此, 寻找开发其他的降脂药具有重要意义。
本研究采用高脂饲料(组成: 20%蔗糖、15%猪油、1.2%胆固醇、0.2%胆酸钠)喂养SD大鼠2周, 经血脂生化检测, 构建了混合型高脂血症模型。与正常组相比, 模型组大鼠的血清TG、TC和LDL-c (P<0.01)水平极显著升高, 而HDL-c (P<0.05)水平显著降低, 这与高脂饮食引起的代谢紊乱相符且与相关报道一致[23-24]。NMN (10、50、250 mg/kg)干预后, 这些血脂指标得到了显著改善, 特别是TG、TC和LDL-c (P<0.05)的显著降低, 且呈剂量依赖性。各干预组大鼠的体重与模型组相比, 也增长缓慢, 其中中和高剂量组的体重增长趋势一致。目前, MILLS等[25]分别用100和300 mg/kg剂量的NMN作用小鼠12个月, 有效缓解小鼠与年龄相关的生理衰退, 减少由年龄带来的体重增加, 并增加胰岛素敏感性, 降低血脂水平, 呈剂量依赖。TIAN等[26]研究发现通过补充NMN恢复NAD+的水平, 来降低HFD小鼠的血脂。LI等[27]研究发现补充NMN增加NAD+的水平, 改善了HFD小鼠肝脏的氧化应激和线粒体功能障碍, 从而使脂质代谢紊乱减轻。本研究在给予SD大鼠补充NMN也有降血脂作用。
肝脏是机体脂类物质合成和分解的重要器官[28]。高脂血症的发生是破坏了体内脂质代谢的平衡, 导致体内过多的脂类物质以脂滴方式储存于肝细胞中, 造成肝脏发生脂肪变性, 可进一步导致肝细胞损伤或肝功能障碍。其中ALT主要分布在肝细胞胞浆中, AST分布在线粒体中, 它们作为肝脏内关键的功能性酶, 可从受损的肝细胞或死亡的肝细胞中分泌进入血液; 同时, 肝细胞受损又会增加血脂水平, 从而形成了脂质代谢的恶性循环[29-31]。本研究的结果显示, NMN显著降低了ALT (P<0.05)和AST的水平, 这些酶的活性通常在肝细胞损伤时升高。此外, 高剂量NMN对AST (P<0.05)的降低效果更为显著, 这可能表明更高剂量的NMN具有更强的肝脏保护作用。肝脏病理组织学观察也支持了这一点, 且高剂量NMN的NAS评分是最低, 也显示出高剂量NMN干预后大鼠肝脏损伤较轻。
尽管NMN的降脂和肝脏保护作用能为高脂血症和相关肝脏疾病的治疗提供了新的视角, 并且具有开发成为减肥降脂功能性食品及保健品的潜力, 但其具体作用机制仍需进一步探究。此外, 长期使用NMN的安全性和有效性, 以及它对人类健康的具体影响仍需要更多的临床试验来验证。
  • 安徽省卫生健康委科研项目(AHWJ2023A30153)
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doi: 10.19812/j.cnki.jfsq11-5956/ts.20240926003
  • 接收时间:2024-09-26
  • 首发时间:2025-07-14
  • 出版时间:2025-06-15
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  • 收稿日期:2024-09-26
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安徽省卫生健康委科研项目(AHWJ2023A30153)
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    安徽省疾病预防控制中心, 合肥 230601

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* 杨同金(1982—), 男, 硕士, 副主任技师, 主要研究方向为毒性病理学。E-mail:
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2种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

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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