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烟酰胺单核苷酸通过Sirt3减轻心脏死亡供肝诱导的缺血-再灌注损伤

贾志兴, 程颖, 李慧源, 等. 烟酰胺单核苷酸通过Sirt3减轻心脏死亡供肝诱导的缺血-再灌注损伤[J]. 器官移植, 2022, 13(5): 618-625. doi: 10.3969/j.issn.1674-7445.2022.05.011
引用本文: 贾志兴, 程颖, 李慧源, 等. 烟酰胺单核苷酸通过Sirt3减轻心脏死亡供肝诱导的缺血-再灌注损伤[J]. 器官移植, 2022, 13(5): 618-625. doi: 10.3969/j.issn.1674-7445.2022.05.011
Jia Zhixing, Cheng Ying, Li Huiyuan, et al. Nicotinamide mononucleotide attenuates ischemia-reperfusion injury induced by donor liver from cardiac death through Sirt3[J]. ORGAN TRANSPLANTATION, 2022, 13(5): 618-625. doi: 10.3969/j.issn.1674-7445.2022.05.011
Citation: Jia Zhixing, Cheng Ying, Li Huiyuan, et al. Nicotinamide mononucleotide attenuates ischemia-reperfusion injury induced by donor liver from cardiac death through Sirt3[J]. ORGAN TRANSPLANTATION, 2022, 13(5): 618-625. doi: 10.3969/j.issn.1674-7445.2022.05.011

烟酰胺单核苷酸通过Sirt3减轻心脏死亡供肝诱导的缺血-再灌注损伤

doi: 10.3969/j.issn.1674-7445.2022.05.011
基金项目: 

河南省医学科技攻关计划联合共建项目 LHGJ20200507

新乡医学院第一附属医院青年培育基金项目 QN-2021-B12

详细信息
    作者简介:
    通讯作者:

    贾德功,主治医师,研究方向为器官移植,Email:jdgsci@163.com

  • 中图分类号: R617, R575

Nicotinamide mononucleotide attenuates ischemia-reperfusion injury induced by donor liver from cardiac death through Sirt3

More Information
  • 摘要:   目的  探讨烟酰胺单核苷酸(NMN)对大鼠心脏死亡供肝诱导的缺血-再灌注损伤(IRI)的作用及机制。  方法  通过“磁环+双袖套”法建立大鼠原位肝移植模型。将SD大鼠随机分为假手术组(Sham组)、原位肝移植组(OLT组)、NMN处理+原位肝移植组(NMN组)、NMN+去乙酰化酶-3(Sirt3)抑制剂(3-TYP)+原位肝移植组(NMN+3-TYP组)。观察各组大鼠肝组织病理学改变及肝细胞凋亡情况,检测血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平,测定肝组织超氧化物歧化酶(SOD)和丙二醛(MDA)含量,检测肝组织Sirt3、微管相关蛋白1轻链3(LC3)Ⅱ、PTEN诱导假定激酶1(PINK1)、Parkin、线粒体外膜转位酶20(TOMM20)表达水平。分析各组大鼠术后生存情况。  结果  与Sham组比较,OLT组ALT、AST水平升高;与OLT组比较,NMN组ALT、AST水平均下降;与NMN组比较,NMN+3-TYP组ALT、AST水平升高(均为P < 0.05)。Sham组大鼠肝组织结构基本正常;OLT组大鼠肝组织可见明显的淤血、空泡变性和肝细胞坏死等病理改变。OLT组Suzuki评分、细胞凋亡率较Sham组升高;NMN组Suzuki评分、细胞凋亡率较OLT组降低;NMN+3-TYP组Suzuki评分、细胞凋亡率较NMN组升高(均为P < 0.05)。与Sham组比较,OLT组SOD含量下降,MDA含量升高;与OLT组比较,NMN组SOD含量升高,MDA含量下降;与NMN组比较,NMN+3-TYP组SOD含量下降,MDA含量升高(均为P < 0.05)。与Sham组比较,OLT组Sirt3、TOMM20蛋白相对表达量下降,PINK1、Parkin、LC3Ⅱ蛋白相对表达量升高;与OLT组比较,NMN组Sirt3、PINK1、Parkin、LC3Ⅱ蛋白相对表达量升高,TOMM20蛋白相对表达量下降;与NMN组比较,NMN+3-TYP组PINK1、Parkin、LC3Ⅱ蛋白相对表达量下降,TOMM20蛋白相对表达量升高(均为P < 0.05)。Sham组、OLT组、NMN组、NMN+3-TYP组大鼠术后7 d生存率分别为100%、50%、75%、58%。  结论  NMN可通过上调Sirt3,增强肝脏抗氧化能力及诱导PINK1/Parkin介导的线粒体自噬,减轻肝IRI,从而对心脏死亡供肝发挥保护作用。

     

  • 图  1  各组大鼠肝功能血清学指标

    注:A图为各组大鼠肝移植术后6 h ALT水平;B为各组大鼠肝移植后6 h AST水平。与Sham组比较,aP < 0.05;与OLT组比较,bP < 0.05;与NMN组比较,cP < 0.05。

    Figure  1.  Serological indexes of liver function of rats in each group

    图  2  各组大鼠肝组织病理学表现

    注:A图为各组大鼠肝移植术后6 h肝组织病理学检测结果(HE,上图×200,下图×400);B图为各组Suzuki评分比较。与Sham组比较,aP < 0.05;与OLT组比较,bP < 0.05;与NMN组比较,cP < 0.05。

    Figure  2.  Hepatic histopathological features of rats in each group

    图  3  各组大鼠肝细胞凋亡情况

    注:A图为各组大鼠肝移植术后6 h肝细胞凋亡检测结果(TUNEL,×400);B图为各组细胞凋亡率比较。与Sham组比较,aP < 0.05;与OLT组比较,bP < 0.05;与NMN组比较,cP < 0.05。

    Figure  3.  Hepatocyte apoptosis of rats in each group

    图  4  各组大鼠氧化应激水平

    注:A图各组大鼠术后6 h肝组织SOD的含量;B图各组大鼠术后6 h肝组织MDA的含量。与Sham组比较,aP < 0.05;与OLT组比较,bP < 0.05;与NMN组比较,cP < 0.05。

    Figure  4.  The levels of oxidative stress of rats in each group

    图  5  各组大鼠肝组织线粒体自噬相关蛋白表达情况

    注:与Sham组比较,aP < 0.05;与OLT组比较,bP < 0.05;与NMN组比较,cP < 0.05。

    Figure  5.  Expression of mitophagy-related proteins in liver tissue of rats in each group

    图  6  各组大鼠肝移植术后生存率

    Figure  6.  Survival rate of rats in each group after liver transplantation

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出版历程
  • 收稿日期:  2022-04-24
  • 网络出版日期:  2022-09-14
  • 刊出日期:  2022-09-15

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