摘要
目的研究地黄多糖对糖尿病肾病(diabetic nephropathy,DN)大鼠的治疗作用并初步探索其分子机制。方法注射链脲佐菌素(streptozotocin,STZ)诱导糖尿病肾病大鼠模型,分为模型组,地黄多糖低剂量组(10 mg/kg)、中剂量组(20 mg/kg)、高剂量组(30 mg/kg),罗格列酮处理组以及正常对照组。检测各组大鼠24 h尿蛋白、肾质量指数(肾质量/体质量)和血糖以及肾功能参数三酰甘油(TG)、尿素氮(BUN)及肌酐(Scr)水平。酶联免疫吸附试验(ELISA)检测各组大鼠血清中转化生长因子(TGF)-β含量。逆转录-聚合酶链反应(RT-PCR)和免疫印迹实验(Western blot)检测各组大鼠骨骼肌中过氧化物酶体增殖物激活受体γ(PPARγ)、脂肪细胞脂肪酸结合蛋白(a P2)和葡萄糖转运蛋白4(GLU4)mRNA和蛋白表达水平。结果糖尿病肾病大鼠模型(DN模型)24 h蛋白、肾质量指数、血糖、TGF-β、TG、BUN和Scr高于正常对照组(P<0.05),PPARγ、a P2和GLUT4水平低于正常对照组(P<0.05),显示造模成功。随着地黄多糖剂量增加,a P2/GAPDH和GLUT4/GAPDH水平增高(P<0.05),其余指标随着剂量增加而降低(P<0.05)。高剂量组地黄多糖治疗效果略低于罗格列酮组。模型组DN大鼠骨骼肌中PPARγ、a P2和GLUT4蛋白水平显著低于对照组(P<0.05),地黄多糖能够明显上调各蛋白表达水平。结论地黄多糖能够通过调节PPARγ信号通路相关蛋白的表达对糖尿病肾病大鼠起到治疗作用,且该治疗作用有剂量依赖性。
Objective To investigate therapeutic effect and molecular mechanism of RPS on Diabetic Nephropathy rats. Methods DN rats were induced by STZ injection and grouped into model group,low-dose RPS group,middle-dose RPS group,high-dose RPS group,Rosiglitazone group and normal group. 24 h urine protein,kidney weight index,blood glucose level and TG,BUN and Scr level in normal and DN rats were detected. TGF-β level of serum of rats in all groups by ELISA were detected. mRNA and protein expression level of PPARγ,a P2 and GLUT4 by RT PCR and Western blot were also detected. Results DN rats were induced successfully because the 24 h urine protein,kidney weight index and the levels of blood sugar and TG,BUN,Scr l and TGF-βevels,and the mRNA level of PPARγ,a P2 and GLUT4 level in DN rats increased than normal group（ P〈0. 05）. The mRNA level of PPARγ,a P2 and GLUT4 level increased（ P〈0. 05） and other indexes decreased（ P〈0. 05） as the doses of RPS increasing. The therapeutic effects of Rosiglitazone group was better than high dose PRS group. The protein level of PPARγ,a P2 and GLUT4 in DN rat skeletal muscle were significantly lower than normal group（ P〈0. 05）,and RPS can increase their expression level obviously. Conclusion RPS has a dose-dependent therapeutic effect on DN rats by improving the expression level of related protein in PPAR gamma signaling pathways.
出处
《中国生化药物杂志》
CAS
2015年第9期30-33,37,共5页
Chinese Journal of Biochemical Pharmaceutics
