基于TLR4/MyD88/TRIF信号通路探讨“从风论治”治疗糖尿病肾病作用机制  

Exploration of the Mechanism of“Treating Diabetic Kidney Disease from Wind”Based on TLR4/MyD88/TRIF Signaling Pathway

作　　者：王羲文 赵进喜[2] WANG Xiwen;ZHAO Jinxi(Beijing University of Traditional Chinese Medicine,Beijing 100700,China;Dongzhimen Hospital,Beijing University of Traditional Chinese Medicine,Beijing 100700,China)

机构地区：[1]北京中医药大学,北京100700 [2]北京中医药大学东直门医院,北京100700

出　　处：《辽宁中医药大学学报》2025年第3期17-20,F0003,共5页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(82074354)。

摘　　要：目的基于Toll样受体4(Toll-like receptor 4,TLR4)/髓分化因子88(myeloid differential protein-88,MyD88)/β干扰素TIR结构域衔接蛋白(TIR-domain containing adaptor inducing interferon-β,TRIF)信号通路探索“从风论治”法治疗糖尿病肾病(diabetic kidney disease,DKD)的作用机制。方法db/db小鼠分为对照组、糖尿病肾病组和益气祛风方组,药物干预时限为8周。留存血清、尿液备用,检测24 h尿蛋白定量、白细胞介素-1(interleukin-1,IL-1)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)的表达水平。留取肾组织,光镜下观察肾组织病理改变,同时采用Western Blot以及免疫组化法检测肾脏组织中TLR4、MyD88、TRIF、TNF受体关联因子6(TNF-receptor associated factor 6,TRAF6)蛋白的相对表达情况。结果药物干预后,与糖尿病肾病组相比,益气祛风方组24 h尿蛋白明显降低,且差异具有统计学意义。Elisa结果显示:与糖尿病肾病组相比,益气祛风方组TNF-α、IL-1水平明显降低,且差异具有统计学意义(P<0.05)。对照组肾组织的肾小球结构完整,系膜细胞和系膜基质均增生,少量炎症细胞浸润于细胞间质,益气祛风方组较糖尿病肾病组病理情况有所减轻。Western Blot及免疫组化结果显示:与对照组相比,糖尿病肾病组肾组织TLR4、MyD88、TRIF、TRAF6蛋白相对表达水平升高(P<0.05);与糖尿病肾病组相比,益气祛风方组肾组织TLR4、MyD88、TRIF、TRAF6蛋白相对表达水平降低(P<0.05)。结论“从风论治”法通过TLR4/MyD88/TRIF信号通路能够减轻糖尿病肾病炎症因子的表达,以延缓糖尿病肾病进展。Objective Based on Toll-like receptor 4/myeloid differential protein-88/TIR-domain containing adaptor inducing interferon-β(TLR4/MyD88/TRIF)signaling pathway,explore the mechanism of the treatment of diabetic kidney disease(DKD)with“treating from wind”method.Methods db/db mice were divided into control group,DKD group and Yiqi Qufeng Recipe Decoction(益气祛风方).The duration of drug intervention was eight weeks.Retain serum and urine reserve,measure 24 hour urine protein quantification,interleukin-1(IL-1),and tumor necrosis factor-α(TNF-α)level expression to collect renal tissue and observe pathological changes under light microscopy.At the same time,Western Blot and immunohistochemistry were used to detect the relative expression of TLR4,MyD88,TRIF,and TNF-receptor-associated factor 6(TRAF6)proteins in renal tissue.Results After drug intervention,the Yiqi Qufeng Decoction group showed a significant decrease in 24 hour urinary protein compared to the DKD group,and the difference was statistically significant.Elisa's results showed that compared to the DKD group,the Yiqi Qufeng Decoction group had lower levels of TNF-αand IL-1,with statistical value(P<0.05).In the control group,the glomerulus structure of renal tissue was intact,mesangial cells and mesangial matrix were proliferating,and a small amount of inflammatory cells were infiltrating into the intercellular matrix.The pathological condition of the Yiqi Qufeng Decoction group was less than that of the DKD group.Western blot and immunohistochemical results showed that the relative expression levels of TLR4,MyD88,TRIF and TNF-receptor associated factor 6 protein in renal tissue of DKD group were higher than those of normal control group(P<0.05);Compared with the DKD group,the relative expression levels of TLR4,MyD88,TRIF and TRAF6 proteins in kidney tissue of the Yiqi Qufeng Decoction group decreased(P<0.05).Conclusion“Treating from wind”method can reduce the expression of inflammatory factors in DKD and delay the progression of DKD through TL

关 键 词：TLR4/MyD88/TRIF信号通路 从风论治 糖尿病肾病 

分 类 号：R255.4[医药卫生—中医内科学]