通心络调控 p38 MAPK通路抑制细胞外基质沉积的研究

摘要

Objective To investigate the influence of Tongxinluo( TXL) on renal tissue p38 MAPK signaling pathway, transforming growth factor β1 ( TGF-β1 ) , extracellular matrix FN and Col-Ⅳ in spontaneous T2DM KK-Ay mice, and to explore the mechanism of TXL inhibiting renal fibrosis in diabetic nephropathy. Methods 45 spontaneous T2DM KK-Ay mice were used to induced diabetic nephropathy models, and randomly divided into model group, TXL group and western medicine group, 15 mice in each group. 15 C57BL/6J mice were chosen as the normal group. Diabetic nephropathy models were treated for 12 weeks. Blood glucose( FBG) , body weight( BW) , kidney weight( KW) , index of kidney weight= KW/BW, renal function ( Scr, Urea ) as well as urinary micro-albumin biochemical parameters ( mALB ) were detected;TGF-β1, p38, P-p38, FN, Col-Ⅳ were detected with Western blot. Results Comparing with the normal group, the expressions of FBG, urinary micro-albumin, Scr, Urea were significantly increased (P<0. 05), and the expressions of TGF-β1, P-p38, FN, Col-Ⅳ were increased(P<0. 05). On the other hand, comparing with the model group, the expressions of FBG, urinary micro-albumin, Scr, Urea were decreased in both administration groups(P<0. 05). However, the expression of FBG stayed unchanged (P<0.05). Moreover, there were no differences in all groups in the expressions of p38(P<0. 05). Conclusion TXL had no effect on blood glucose, but it could reduce the expressions of TGF-β1, inhibit the phosphorylation of p38 and affect extracellular matrix deposition, which might become one of the mechanisms for its treatment of DN.%目的：观察通心络对自发性2型糖尿病 KK-Ay小鼠肾组织 p38 MAPK信号通路、TGF-β1及细胞外基质FN、Col-Ⅳ的影响,探讨其抑制糖尿病肾病肾脏纤维化的作用机制。方法采用自发性2型糖尿病KK-Ay小鼠建立糖尿病肾病模型,随机分为模型组、通心络组和缬沙坦组各15只,设C57BL/6J小鼠15只为正常组；造模组连续给药12周,比较各组 KK-Ay小鼠空腹血糖( fasting blood glucose,FBG)、体重( body weight,BW)、肾重( kidney weight,KW)、肾重指数=KW/BW；24小时尿微量白蛋白(24 hours urinary microalbumin,24 h mALB)；血清肌酐( serum creatinine,SCr)、血清尿素(Urea)的水平；检测转化生长因子β1(transforming growth factor-β1,TGF-β1)、p38、P-p38、纤维连接蛋白( fibronectin,FN),Ⅳ型胶原蛋白( Collagen in Serum-Ⅳ,Col-Ⅳ)等表达水平。结果与正常组比较,模型组空腹血糖、体重、肾重、肾重指数、24h mALB、SCr、Urea均明显升高(P<0.05),肾组织P-p38、FN、Col-Ⅳ蛋白表达升高(P<0.05)。与模型组比较,通心络组和缬沙坦组FBG无明显变化(P>0.05)；体重、肾重减轻、肾重指数、24h mALB、SCr、Urea均降低(P<0.05),肾组织P-p38、FN、Col-Ⅳ蛋白表达减少(P<0.05),但给药组间无显著差异(P>0.05)。各组间p38表达均无统计学差异(P>0.05)。结论提示通心络无明显降糖作用；通心络可降低自发性2型糖尿病KK-Ay小鼠24 h mALB、SCr、Urea,保护肾功能；通心络可抑制TGF-β1、P-p38蛋白的过度表达,减少FN、Col-Ⅳ等细胞外基质在肾组织的沉积,从而抑制肾脏的纤维化,延缓糖尿病肾病的发生发展。