雷公藤多苷对过敏性紫癜肾炎大鼠的影响机制研究OA
Mechanism of effect of tripterygium wilfordii glycosides on rats with henoch-schonlein purpura nephritis
目的:探讨雷公藤多苷(GTW)对过敏性紫癜肾炎(HSPN)大鼠肾组织的保护机制,及其对Toll样受体4(TLR4)信号介导的M1/M2型巨噬细胞极化的调控机制.方法:采用牛血清白蛋白(BSA)+LPS+四氯化碳(CCl4),辅以干姜水灌胃形成瘀热刺激,复合影响制备HSPN大鼠模型;实验分组如下:对照组、模型组(HSPN)、GTW低(GTW-L)、GTW高(GTW-H)剂量组、激动剂组(LPS).自动生化仪检测各组大鼠的24 h尿蛋白定量及肾功能;ELISA测定各组大鼠血清中IL-6及TNF-α含量;TUNEL染色检测肾组织中细胞凋亡率,免疫组化检测大鼠肾组织巨噬细胞极化;Western blot检测各组大鼠肾组织中TLR4、髓样分化因子88(MyD88)、NF-κB、p-NF-κB、Bcl-2和Bax表达.结果:GTW能明显降低HSPN大鼠的24 h尿蛋白定量,改善大鼠肾功能,降低血清中IL-6和TNF-α含量,下调肾组织中的细胞凋亡率,抑制TLR4的信号传导,降低TLR4、MyD88、p-NF-κB和Bax表达,提高Bcl-2表达,而LPS可部分逆转GTW对肾组织的保护作用,差异均具有统计意义(均P<0.05).结论:GTW能明显抑制HSPN大鼠肾组织中炎症介质表达,降低肾组织细胞凋亡率,减轻大鼠肾组织病理损伤,改善大鼠肾功能,可能与其能抑制TLR4信号表达,推动肾组织巨噬细胞向M2型转换有关.
Objective:To investigate the protective effect of tripterygium wilfordii glycosides(GTW)on kidney in rats with henoch-schonlein purpura nephritis(HSPN),and its regulation on polarization of M1/M2 macrophages mediated by Toll-like receptor 4(TLR4)signaling pathway.Methods:Rat model of HSPN was established by intragastric administration of bovine serum albumin(BSA)+LPS+carbon tetrachloride(CCl4),supplemented with dried ginger water.Experimental groups were as follows:control group,model group(HSPN),GTW low dose group(GTW-L),GTW high dose group(GTW-H),agonist group(LPS).Automatic biochemi-cal instrument was used to detect 24-hour urinary protein and renal function.ELISA was used to determine contents of IL-6 and TNF-α in serum of rats in each group.TUNEL staining was used to detect apoptosis rate in renal tissue,immunohistochemistry was used to de-tect the polarization of macrophages in rat renal tissue.Western blot was used to detect expressions of TLR4,myeloid differentiation factor 88(MyD88),NF-κB,p-NF-κB,Bcl-2 and Bax.Results:GTW could significantly reduce the quantity of 24-hour urinary pro-tein,improve renal function,decrease contents of IL-6 and TNF-α in serum,down-regulate rate of apoptosis in renal tissue,inhibit sig-nal transduction of TLR4,decrease expressions of TLR4,MyD88,NF-κB and Bax,increase expression of Bcl-2,while LPS could partially reverse the protective effect of GTW on renal tissue,and the differences were statistically significant(all P<0.05).Conclu-sion:GTW can significantly inhibit expressions of inflammatory mediators in renal tissue of HSPN rats,reduce apoptosis rate of renal tissue,reduce the pathological injury of renal tissue,and improve the renal function of rats,which may be related to its ability to inhibit the expression of TLR4 signaling pathway and promote the conversion of renal macrophages to type M2.
郑晓娟
郑州市中医院儿科,郑州 450003
医药卫生
雷公藤多苷过敏性紫癜肾炎Toll样受体4信号通路巨噬细胞极化
Tripterygium wilfordii glycosidesHenoch-schonlein purpura nephritisToll-like receptor 4 signaling pathwayMacrophage polarization
《中国免疫学杂志》 2026 (4)
794-800,807,8
河南省中医药传承与创新第二批拔尖人才培养项目(豫卫中医函[2021]15号)河南省中医药科学研究专项课题(2023ZY2157).
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