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基于NLRP3炎性小体通路探讨金樱子乙醇提取物对系膜增生性肾小球肾炎大鼠的保护作用 被引量:21

Protective effect of ethanol extract of Rosa laevigata michx.on mesangial prolifera-tive glomerulonephritis in rats based on NLRP3 inflammatory corpuscle pathway
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摘要 目的:探究金樱子乙醇提取物(RLM)对系膜增生性肾小球肾炎(MsPGN)大鼠的保护作用,并初步探究其作用机制。方法:将SD大鼠分为假手术组(Sham),MsPGN组,金樱子乙醇提取物低、中、高剂量组(RLM-L、RLM-M、RLM-H),阳性对照组(醋酸泼尼松组,Prednisone acetate),每组12只大鼠,给药4周后收集24 h蛋白尿液处死大鼠,观察各组大鼠体重变化情况,检测血清肾功能相关指标肌酐(Scr)、尿素氮(BUN)等;HE染色检测肾组织病理形态学变化;蛋白免疫印迹法(WB)、免疫组化法检测肾组织中NLRP3、凋亡相关斑点样蛋白(ASC)、半胱天冬酶(caspase-1)表达;ELISA法检测肾组织匀浆中IL-1β和IL-18表达。结果:与Sham组相比,MsPGN组大鼠体重降低,24 h尿蛋白、BUN、Scr水平升高,TP、ALB水平降低,肾组织损伤评分升高,肾组织中NLRP3、ASC和caspase-1蛋白表达升高,组织匀浆中IL-1β、IL-18水平升高(P<0.05);与MsPGN组相比,RLM-L、RLM-M、RLM-H、Prednisone acetate组大鼠体重升高,24 h尿蛋白、BUN、Scr降低,TP、ALB水平升高,肾组织损伤评分降低,肾组织中NLRP3、ASC、caspase-1蛋白表达降低,组织匀浆中IL-1β、IL-18水平降低(P<0.05)。结论:RLM对MsPGN大鼠肾脏损伤具有保护作用,这种作用可能通过抑制NLRP3炎性小体通路,进而抑制通路介导的促炎性因子IL-1β和IL-18的表达,最终缓解肾损伤。 Objective:To investigate the protective effect of ethanol extract of Rosa laevigata michx.(RLM)on mesangial proliferative glomerulonephritis(MsPGN)rats and to explore its mechanism.Methods:SD rats were divided into sham group(Sham),MsPGN group,low,medium and high dose ethanol extract of Rosa laevigata michx.groups(RLM-L,RLM-M,RLM-H)and positive control group(Prednisone acetate group),with 12 rats in each group.After 4 weeks of administration,24 h urinary protein were collected and the rats were killed.The changes of body weight were observed,serum creatinine(Scr)and urea nitrogen(BUN)were detected,HE staining was used to detect the pathological changes of renal tissue,the expressions of NLRP3,ASC and caspase-1 in renal tissue were detected by Western blot(WB)and immunohistochemistry,and the expressions of IL-1βand IL-18 in renal homogenate were detected by ELISA.Results:Compared with Sham group,the weight of rats in MsPGN group decreased,the levels of 24 h urinary protein,BUN and Scr increased,the levels of TP and ALB decreased,the score of renal tissue injury increased,the expressions of NLRP3,ASC and caspase-1 proteins in renal tissue increased,and the levels of IL-1βand IL-18 in tissue homogenate increased(P<0.05).Compared with MsPGN group,the weight of rats in RLM-L,RLM-M,RLM-H,Prednisone acetate groups increased,the levels of 24 h urinary protein,BUN and Scr decreased,the levels of TP and ALB increased,the score of renal tissue injury decreased,the expressions NLRP3,ASC and caspase-1 proteins in renal tissue increased,and the levels of IL-1βand IL-18 in tissue homogenate decreased(P<0.05).Conclusion:RLM has protective effect on renal injury in MsPGN rats,which may inhibit the expression of IL-1βand IL-18 mediated by NLRP3 inflammatory body pathway,and ultimately relieve kidney damage.
作者 林艳梅 彭庆海 陈杰 林小小 LIN Yan-Mei;PENG Qing-Hai;CHEN Jie;LIN Xiao-Xiao(Clinical Drug Trial Department,the People′s Hospital of Pingxiang,Pingxiang 337000,China)
出处 《中国免疫学杂志》 CAS CSCD 北大核心 2020年第5期560-565,共6页 Chinese Journal of Immunology
基金 萍乡市2018年度市级科技计划项目(No.2018PY024)。
关键词 系膜增生性肾小球肾炎 金樱子乙醇提取物 NLRP3炎性小体 凋亡相关斑点样蛋白 半胱天冬酶 Mesangial proliferative glomerulonephritis Ethanol extract of Rosa laevigata michx Inflammatory body of NLRP3 Apoptosis-related spot-like protein Caspase-1
作者简介 林艳梅,女,副主任药师,主要从事医院药学及药物临床试验方面的研究,E-mail:duye200062@163.com;通讯作者及指导教师:彭庆海,男,副主任药师,主要从事医院药学及药物临床试验方面的研究,E-mail:1816524594@qq.com。
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