摘要
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 m ALB);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 m ALB、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 m ALB、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 m ALB、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。
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 T2 DM KK-Ay mice,and to explore the mechanism of TXL inhibiting renal fibrosis in diabetic nephropathy. Methods 45 spontaneous T2 DM 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. 15C57 BL /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,renalfunction（ Scr,Urea） as well as urinary micro-albumin biochemical parameters（ m ALB） 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.
出处
《环球中医药》
CAS
2017年第2期146-150,共5页
Global Traditional Chinese Medicine
基金
国家重点基础研究发展计划(973计划)(2012CB518602)
