基于TLR4/NF-κB信号通路探讨何首乌提取物二苯乙烯苷对糖尿病肾病早期大鼠的影响

Effect of tetrahydroxystilbene glucoside of Polygonum multiflorum extract on early diabetic nephropathy rats based on TLR4/NF-κB signaling pathway

目的探讨何首乌提取物对单侧肾切除联合链脲佐菌素(STZ)诱导的糖尿病肾病(DN)大鼠的影响。方法 60只SPF级雄性Wistar大鼠成功造模后,按照随机数字表法分为对照组,模型组,厄贝沙坦组,二苯乙烯苷(TSG)低、中、高剂量组,每组10只。各组大鼠每日灌服相应剂量的药物,对照组和模型组每日灌服相应体积的蒸馏水。记录并分析各组小鼠的各项指标。结果与对照组比较,模型组体重、核因子(NF)-κB抑制蛋白(IκBα)表达量显著降低,肾指数,血清肌酐(Scr)、尿素氮(UN)水平,24 h尿蛋白含量,白细胞介素(IL)-1β、IL-6和单核细胞趋化蛋白1(MCP-1)水平及m RNA表达,Toll样受体4(TLR4)、NF-κB p65及磷酸化(p)-IκBα蛋白表达量显著升高,肾小球受损程度较重,差异有高度统计学意义(P <0.01)。与模型组比较,各实验组体重明显升高,Scr、UN水平,24 h尿蛋白含量,IL-1β、IL-6、MCP-1水平,TLR4、NF-κB p65和p-IκBα蛋白表达水平明显下降,肾小球受损程度明显好转,差异有高度统计学意义(P <0.01)。结论 TSG可能通过下调TLR4/NF-κB信号通路抑制炎性因子的生成,从而保护DN大鼠的肾脏组织。

Objective To explore the effect of Polygonum multiflorum extract on unilateral nephrectomy combined with streptozotocin(STZ)-induced diabetic nephropathy(DN)rats.Methods A total of 60 SPF male Wistar rats were successfully modeled,while divided into control group,model group,irbesartan group,tetrahydroxystilbene glucoside(TSG)low,medium and high dose groups,with 10 rats in each group.Rats were given the corresponding dose of drugs daily,while the control and the model group were infused with a corresponding volume of distilled water.Indexes of rats in each group were recorded and analyzed.Results Compared with the control group,body weight and nuclear factor(NF)-κB inhibition(IκBα)protein expression were reduced in the model group,renal index,the level of serum creatinine(Scr),urea nitrogen(UN),24 h urine protein content,the levels and m RNA expression of interleukin(IL)-1β,IL-6 and monocyte chemoattractant protein 1(MCP-1),and the protein expression of Toll-like receptor 4(TLR4),NF-κB p65 and phosphorylated(p)-IκBαwere significantly increased,while the glomerular damage was severe,and the differences were highly statistically significant(P<0.01).Compared with the model group,the weight of each experimental group was significantly increased,the levels of Scr,UN,24 h urine protein content,IL-1β,IL-6,MCP-1,the protein expression of TLR4,NF-κB p65 and p-IκBαwere significantly decreased,while the degree of glomerular damage was significantly improved,and the differences were highly statistically significant(P<0.01).Conclusion TSG may in-hibit the formation of inflammatory factors by down-regulating TLR4/NF-κB signaling pathway to protect the kidney tissue of DN rats.