基于TLRs/MyD88信号通路探讨丹蛭降糖胶囊对糖尿病肾病大鼠的作用机制研究  

Exploring the mechanism of Danzhi Jiangtang Capsule on diabetic kidney disease in rats based on TLRs/MyD88 signaling pathway

作　　者：鲍陶陶[1] 孟利亚 黄展鹏[1] 方舟 方朝晖[2] BAO Tao-tao;MENG Li-ya;HUANG Zhan-peng;FANG Zhou;FANG Zhao-hui(Anhui University of Chinese Medicine,Hefei 230038,China;First Affiliated Hospital of Anhui University of Chinese Medicine,Hefei 230031,China)

机构地区：[1]安徽中医药大学,安徽合肥230038 [2]安徽中医药大学第一附属医院,安徽合肥230031

出　　处：《时珍国医国药》2024年第9期2076-2080,共5页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金(82174153,81774286);安徽省高校自然科学基金项目(KJ2021A0560)。

摘　　要：目的基于Toll样受体(TLRs)/髓样分化因子88(MyD88)通路探讨丹蛭降糖胶囊对糖尿病肾病大鼠肾脏损伤的干预作用及机制。方法将60只SD大鼠随机分为空白组、模型组、缬沙坦组和丹蛭降糖胶囊组,干预16周,观察各组大鼠一般状况的变化、生化法测定糖脂代谢、肾功能相关指标;酶联免疫吸附法检测相关炎症因子水平;实时荧光定量聚合酶链式反应检测TLR2、TLR4、MyD88 mRNA表达水平;蛋白免疫印迹法检测自噬相关因子Beclin1、LC3-I、LC3-II的表达水平;透射电镜观察大鼠肾组织细胞;流式细胞仪检测肾足细胞活性氧水平;细胞计数法检测细胞增殖情况。结果与模型组大鼠相比,丹蛭降糖组及缬沙坦组大鼠生存质量提高,糖脂代谢、肾功能相关指标显著改善(P<0.01),IL-1β、TNF-α水平降低,IL-10水平升高(P<0.05),肾组织细胞中TLR2、TLR4、MyD88 mRNA表达增加(P<0.05),Beclin1、LC3-I、LC3-II蛋白表达水平降低(P<0.05),肾脏组织病理均有不同程度改善,氧化应激水平减少,细胞增殖增加(P<0.05)。结论丹蛭降糖胶囊能提高糖尿病肾病大鼠生存质量,减少细胞过度自噬,减轻肾脏细胞损伤,其作用机制可能与调节TLRs/MyD88信号通路有关。Objective To investigate the interventional effect and mechanism of Danzhi Jiangtang Capsule on renal injury in dia-betic nephropathy rats based on Toll-like receptors(TLRs)/myeloid differentiation factor 88(MyD88)pathway.Methods Six-ty SD rats were randomly divided into a blank group,a model group,a valsartan group,and a Danzhi Jiangtang Capsule group.After 16 weeks of intervention,changes in the general condition of the rats in each group were observed.Biochemical methods were used to measure glucose and lipid metabolism,and renal function-related indicators.Inflammatory factor levels were detec-ted by enzyme-linked immunosorbent assay.TLR2,TLR4,and MyD88 mRNA expression levels were detected by real-time fluorescent quantitative polymerase chain reaction.The expression levels of autophagy-related factors Beclin1,LC3-I,and LC3-II were detected by Western blot.Renal tissue cells of rats were observed by transmission electron microscopy.Reactive oxygen species levels in renal podocytes were detected by flow cytometry.Cell proliferation was measured by cell counting.Results Com-pared with the model group,rats in the Danzhi Jiangtang Capsule group and the valsartan group showed improved quality of life,significant improvement in glucose and lipid metabolism,and renal function-related indicators(P<0.01).Levels of IL-1βand TNF-αwere reduced,while IL-10 levels were elevated(P<0.05).TLR2,TLR4,and MyD88 mRNA expression in re-nal tissue cells increased(P<0.05),while Beclin1,LC3-I,and LC3-II protein expression levels decreased(P<0.05).Renal tissue pathology improved to varying degrees,oxidative stress levels decreased,and cell proliferation increased(P<0.05).Conclusion Danzhi Jiangtang Capsule can improve the quality of life of diabetic nephropathy rats,reduce excessive auto-phagy of cells,and attenuate renal cell injury.Its mechanism of action may be related to the regulation of the TLRs/MyD88 signa-ling pathway.

关 键 词：丹蛭降糖胶囊 糖尿病肾病 TLRs/MyD88信号通路 细胞自噬 

分 类 号：R285.5[医药卫生—中药学]