摘要
目的:探讨止消通脉宁干预糖尿病肾病小鼠肾间质纤维化作用机制。方法:50只12周龄KKAy小鼠成模后随机分为模型组、厄贝沙坦组、止消通脉宁(ZXTMN)高、中、低剂量组,另设10只C57BL/6为正常组。实验期间,记录小鼠一般状态,血糖,24h尿蛋白定量,血清肌酐(Scr),肾组织Masson染色。Western Blot检测肾α-SMA,TGF-β1,BMP-7和VEGF蛋白表达,实时荧光定量PCR检测肾TGF-β1 mRNA,TGF-βR1 mRNA和Smad2 mRNA表达。结果:与模型组相比较,第4周时,ZXTMN治疗组和厄贝沙坦组小鼠体质量、血糖和24h尿蛋白定量显著性减小(P<0.05),肾间质纤维化评分显著性减低(P<0.05)。ZXTMN高、中组和厄贝沙坦组α-SMA和TGF-β1蛋白表达显著性减少(P<0.01),BMP-7和VEGF蛋白表达显著性增加(P<0.01);ZXTMN各治疗组TGF-β1 mRNA和Smad2 mRNA显著性减少(P<0.01)。结论:调节TGF-β1/Smad抑制肾小管上皮细胞转分化可能是止消通脉宁治疗糖尿病肾病肾间质纤维化的分子机制之一。
Objective： Study on mechanism of action of traditional Chinese preparation Zhixiaotongmaining in renal interstitial fibrosis （RIF） of mouse with diabetic nephropathy. Methods： Fifty healthy 12-week-old male KKAy mice and ten C57BL/6 12-week-old mice were randomly divided into Vehicle group, model group, Valsartan group and Zhixiaotongmaining （ZXTMNN） high-, medium-, low-dose group. Then we recorded the general state of the mice, detected the blood glucose, urine protein quantification,Scr in 24h, levels of serum creatinine （Scr） and Masson staining of kidney; we detected the protein expressions of u-SMA, TGF-β1, BMP-7 and VEGF of nephridial tissue with Western Blot; and analyzed the expression of TGF-β1 mRNA, TGF-β R1 mRNA and Smad2 mRNA of nephridial tissue with Real-time RT-PCR. Results： ZXTMN and valsartan could drop body weight, blood glucose and the 24h urine protein. The quantitative and semi-quantitative analysis of RIF results of the mice were significant （P〈0.05） in the fourth week. The protein expressions of ct-SMA and TGF-β1 of the mice in the Valsartan group, high- and medium-dose ZXTMN groups dropped significantly （P〈0.01）. And the protein expressions of BMP-7 and VEGF both increased significantly （P〈0.01）. The expressions of TGF-β1 mRNA and Smad2 mRNA in the high-, medium- and low-ZXTMN groups dropped significantly （P〈0.01）. Conclusion： Regulating renal TGF-β1/Smad signal pathway might be one of the mechanisms of ZXTMN therapeutic effect of DN.
出处
《中华中医药杂志》
CAS
CSCD
北大核心
2013年第5期1466-1470,共5页
China Journal of Traditional Chinese Medicine and Pharmacy
基金
International Science and Technology Cooperation Project(No.2009DFA31520)
Innovation Team Project of Beijing University of Chinese Medicine(No.2011-CXTD-19)~~
