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  

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

作　　者：袁强 申开文 张瑞波 王强 吴玉婷 沈俊 Yuan Qiang;Shen Kaiwen;Zhang Ruibo;Wang Qiang;Wu Yuting;Shen Jun(Department of Urology Surgery,the Affiliated Hospital of Guizhou Medical University,Guiyang 550004,China)

机构地区：[1]贵州医科大学附属医院泌尿外科,贵阳550004 [2]贵州医科大学附属医院病理科,贵阳550004

出　　处：《器官移植》2021年第6期733-740,共8页Organ Transplantation

基　　金：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]。

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。Objective To investigate the effect and mechanism of artesunate on renal ischemia-reperfusion injury(IRI)in rat.Methods Twenty-five SD rats were randomly divided into the sham operation group(Sham group),model group(IRI group),low-dose artesunate group(ART-L group),high-dose artesunate group(ART-H group)and NLRP3 inflammasome inhibitor group(INF39 group),with 5 rats in each group.The levels of serum creatinine(Scr),blood urea nitrogen(BUN)and pathological damage of renal tissue were analyzed.The levels of tumor necrosis factor(TNF)-αand interleukin(IL)-6 in serum were quantitatively measured.The expression level of IL-1βin renal tissues was determined by immunohistochemical staining.The expression levels of pyroptosis-related proteins were detected by fluorescent staining and Western blot.Results Compared with the Sham group,the levels of Scr and BUN were higher,the renal tissue injury was aggravated,the expression levels of TNF-α,IL-6 and IL-1βwere higher,and the expression levels of kidney injury molecule(KIM-1),pyroptosis-related protein NOD-like receptor protein 3(NLRP3),cysteinyl aspartate specific proteinase(Caspase-1),Gasdermin D(GSDMD)and IL-1βproteins were higher in the IRI group.Compared with the IRI group,the levels of Scr and BUN were decreased,the renal tissue injury was mitigated,the expression levels of TNF-α,IL-6 and IL-1βwere down-regulated,and the expression levels of KIM-1,NLRP3,Caspase-1,GSDMD and IL-1βproteins were down-regulated in the ART-L,ART-H and INF39 groups.Conclusions Artesunate may inhibit pyroptosis induced by NLRP3 inflammasome,down-regulate the expression levels of pyroptosis-related proteins,reduce the release of inflammatory factors after renal IRI and alleviate renal IRI.

关 键 词：青蒿琥酯 肾移植 缺血-再灌注损伤 NOD样受体蛋白3 细胞焦亡 炎症 血清肌酐 血尿素氮 

分 类 号：R617[医药卫生—外科学]