基于HMGB1/TLR4信号通路评价五味子乙素对2型糖尿病肾病大鼠肾脏功能的保护作用

Evalution of Renal Function Protection of Schisandrin B in Rates with Type 2 Diabetic Nephropathy Based on HMGB1/TLR4 pathway

目的研究五味子乙素(Sch B)对2型糖尿病肾病(DN)大鼠肾脏功能的保护作用及其对HMGB1/TLR4炎性通路的影响。方法 40只SD大鼠随机分为正常对照组、DN组、DN低剂量Sch B组及DN高剂量Sch B组,采用尾静脉注射链脲佐菌素构建DN模型,并同时给予药物治疗。治疗4周后处死大鼠取材,检测谷丙转氨酶(ALT)、尿肌酐(Ucr)、血肌酐(Scr)、血胱抑素C(Cys-c)及内生肌酐清除率(Ccr); HE染色观察大鼠肾脏组织结构变化; Western blot法分析肾脏组织HMGB1、TLR4、IL-1β、IL-6及TNF-α蛋白表达量。结果与正常对照组比较,DN组大鼠Scr、Cys-c及ALT水平显著升高,Ucr、Ccr水平则显著降低(P <0. 05),肾脏组织形态明显异常,并且HMGB1、TLR4、IL-1β、IL-6及TNF-α蛋白表达量均显著升高(P <0. 05);与DN组大鼠比较,经低、高剂量Sch B治疗后大鼠Scr、Cys-c及ALT水平明显降低,Ucr、Ccr水平则显著升高(P <0. 05),并且HMGB1、TLR4、IL-1β、IL-6及TNF-α蛋白表达量均显著降低(P <0. 05)。结论 Sch B可改善DN大鼠肾脏功能,其机制可能与降低HMGB1/TLR4信号蛋白表达、发挥抗炎作用有关。

Objective To study the protective effects of Schisandrin B(SchB)on renal function in rates with type 2 diabetic nephropathy,and investigate the influence of Schisandrin B on HMGB1/TLR4 inflammatory pathway.Methods 40 SD rats were randomly divided into normal control group,diabetic nephropathy(DN)group,DN low-dose of SchB group and DN high-dose of SchB group.The DN model was constructed through the tail vein injection of streptozotocin.The rats in each group were sacrificed after treatment for 4 weeks.The levels of alanine transaminase(ALT),urinary creatinine(Ucr),serum creatinine(Scr),blood cystatin C(Cys-C),and creatinine clearance rate(Ccr)were determined.HE staining was used to observe the histological changes of renal tissues.Western blot were used to detect the expressions of HMGB1,TLR4,IL-1β,IL-6 and TNF-α.Results Compared with control group,the levels of Scr,Cys-c and ALT were gratly increased,while the levels of Ucr and Ccr significnatly decreased in DN group(P<0.05).The kidney tissue morphology in DN rats was abnormal.The expression levels of HMGB1,TLR4,IL-1β,IL-6 and TNF-αin DN group were significantly increased compared with control group(P<0.05).However,after treatment with low-and high-dose SchB,the levels of Scr,Cys-c and ALT were gratly decreased,while the levels of Ucr and Ccr significnatly increased in SchB groups(P<0.05).The expression levels of HMGB1,TLR4,IL-1β,IL-6 and TNF-αin SchB groups were significantly decreased compared with DN group(P<0.05).Conclusion SchB can improve the kidney function of diabetic rats,and its mechanism may be related to the down-regulation of HMGB1/TR4 signaling protein expressions,which plays the anti-inflammatory effects.