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青蒿琥酯通过NLRP3炎症小体抑制细胞焦亡减轻大鼠肾缺血-再灌注损伤

袁强 申开文 张瑞波 王强 吴玉婷 沈俊

袁强, 申开文, 张瑞波, 等. 青蒿琥酯通过NLRP3炎症小体抑制细胞焦亡减轻大鼠肾缺血-再灌注损伤[J]. 器官移植, 2021, 12(6): 733-740. doi: 10.3969/j.issn.1674-7445.2021.06.014
引用本文: 袁强, 申开文, 张瑞波, 等. 青蒿琥酯通过NLRP3炎症小体抑制细胞焦亡减轻大鼠肾缺血-再灌注损伤[J]. 器官移植, 2021, 12(6): 733-740. doi: 10.3969/j.issn.1674-7445.2021.06.014
Yuan Qiang, Shen Kaiwen, Zhang Ruibo, et al. Artesunate alleviates renal ischemia-reperfusion injury in rats by inhibiting pyroptosis via NLRP3 inflammasome[J]. ORGAN TRANSPLANTATION, 2021, 12(6): 733-740. doi: 10.3969/j.issn.1674-7445.2021.06.014
Citation: Yuan Qiang, Shen Kaiwen, Zhang Ruibo, et al. Artesunate alleviates renal ischemia-reperfusion injury in rats by inhibiting pyroptosis via NLRP3 inflammasome[J]. ORGAN TRANSPLANTATION, 2021, 12(6): 733-740. doi: 10.3969/j.issn.1674-7445.2021.06.014

青蒿琥酯通过NLRP3炎症小体抑制细胞焦亡减轻大鼠肾缺血-再灌注损伤

doi: 10.3969/j.issn.1674-7445.2021.06.014
基金项目: 

贵州省卫生健康委科学技术基金 gzwkj2021-220

贵州省科技计划项目 (2018)5779-6

国家自然科学基金培育项目(贵州医科大学附属医院) gyfynsfc(2020)-30

详细信息
    作者简介:

    袁强,男,1993年生,硕士研究生,研究方向为肾移植相关缺血-再灌注损伤与保护,Email: 411057131@qq.com

    通讯作者:

    沈俊,男,1973年生,博士,副主任医师,研究方向为肾移植相关缺血-再灌注损伤与保护,Email: shenjun@gmc.edu.cn

  • 中图分类号: R617

Artesunate alleviates renal ischemia-reperfusion injury in rats by inhibiting pyroptosis via NLRP3 inflammasome

More Information
  • 摘要:   目的  探究青蒿琥酯对大鼠肾缺血-再灌注损伤(IRI)的作用及机制。   方法  将25只SD大鼠随机分为假手术组(Sham组)、模型组(IRI组)、低剂量青蒿琥组(ART-L组)、高剂量青蒿琥酯组(ART-H组)和NLRP3炎症小体抑制剂组(INF39组),每组5只。分析各组大鼠血清肌酐(Scr)、血尿素氮(BUN)水平及肾组织病理损伤情况;检测各组大鼠血清肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6水平;用免疫组织化学染色法检测各组大鼠肾组织IL-1β的表达;免疫荧光染色和蛋白质免疫印迹法检测焦亡相关蛋白的表达。   结果  与Sham组比较,IRI组Scr和BUN水平升高,肾组织损伤较重,炎症因子TNF-α、IL-6、IL-1β表达水平升高,肾损伤分子(KIM)-1及焦亡相关蛋白NOD样受体蛋白3(NLRP3)、半胱氨酸天冬氨酸蛋白酶(Caspase)-1、Gasdermin D(GSDMD)、IL-1β蛋白表达水平均升高;与IRI组比较,ART-L组、ART-H组和INF39组Scr和BUN水平均下降,肾组织损伤均较轻,TNF-α、IL-6、IL-1β表达水平均降低,KIM-1、NLRP3、Caspase-1、GSDMD、IL-1β蛋白表达水平均下降。   结论  青蒿琥酯可抑制NLRP3炎症小体诱导的细胞焦亡,减少肾IRI后焦亡相关蛋白的表达及炎症因子的释放,减轻肾IRI。

     

  • 图  1  各组大鼠肾组织病理学表现

    注: A图为各组大鼠肾IRI后24 h肾组织病理学结果(HE,x400); B图为各组大鼠肾IRI后24 h肾组织病理学结果(PAS,x200)。

    Figure  1.  Renal histopathological features of rats in each group

    图  2  各组大鼠肾功能血清学指标

    注: A图为各组大鼠肾IRI后24hBUN水平; B图为各组大鼠肾IRI后24hScr水平; 与Sham组比较,aP<0.05;与IRI组比较,bP<0.05;与ART-L组比较,cP<0.05。

    Figure  2.  Serum indexes of renal function of rats in each group

    图  3  各组大鼠肾组织KIM-1蛋白表达水平

    注: 与Sham组比较,aP<0.05; 与IRI组比较,bP<0.05; 与ART-L组比较,cP<0.05; 与ART-H组比较,dp<0.05。

    Figure  3.  The expression levels of KIM-1 protein in renal tissues of rats in each group

    图  4  各组大鼠肾组织IL-1β的表达情况

    注: 图示各组大鼠肾IRI后24 h肾组织IL-β的表达(免疫组化,x 200)

    Figure  4.  Expression of IL-1 in renal tissues of rats in each group

    图  5  各组大鼠血清炎症因子的水平

    注: A图示各组大鼠肾IRI后24 h血清TNF-ax水平; B图示各组大鼠肾IRI后24 h血清IL-6水平; 与Sham组比较,aP<0.05; 与IRI组比较,bP<0.05; 与ART-L组比较,cP<0.05。

    Figure  5.  The levels of inflammatory factors in serum of rats in each group

    图  6  各组大鼠肾组织焦亡相关蛋白的表达情况

    注: A图为各组大鼠肾组织焦亡相关蛋白表达情况,与Sham组比较,aP<0.05, 与IRI组比较,bP<0.05,与ART-L组比较,cP<0.05;B图为各组大鼠肾IRI后24 h肾组织NLRP3. Caspase-1的表达情况(免疫荧光,x200); C图为各组大鼠肾IRI后24 h肾组织GSDMD的表达情况(免疫荧光,x200)。

    Figure  6.  Expression of pyroptosis related proteins in renal tissues of rats in each group

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  • 收稿日期:  2021-07-22
  • 刊出日期:  2021-11-15

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