|
|
Effects of alpha-lipoic acid on TGF-β1/Smads signal transduction pathway in cardiac fibroblast under high glucose condition |
WANG Guo-xian, LIU Shan-shan, LI Fei, LI Zhao-gang, LI Rui-fang |
(Department of Pharmacology, Liaoning Medical College, Jinzhou Liaoning 121001, China) |
|
|
Abstract Objective: To investigate the effects of alpha-lipoic acid (α-LA) on TGF-β1/Smads signal transduction pathway in cardiac fibroblasts(CFb) under high glucose condition. Methods: The primarily cultured neonatal rat CFb were divided into five groups in accordance with different nutrient solutions: NG group(Normal Glucose, 5.5 mmol/L glucose),HG group(High Glucose ,25.5 mmol/L glucose),and medication groups: HG+100 μmol/L alpha-lipoic group,HG+200 μmol/L alphalipoic group,HG+300 μmol/L alphalipoic group. CFb prolifertion was measured by thiazolyl blue(MTT) assay. The collagen Ⅰ contents were detected by enzyme linked immunosorbent assay(ELISA), and the protein expression levels of TGF-β1, p-Smad2/3, Smad7 were detected by Western blot. Results: Compared with those of the NG group, in HG group, the CFb proliferation was stimulated, MTT-OD was concomitantly increased(P<0.01),the secretion of collagen Ⅰ was increased(P<0.01),the protein expression levels of TGF-β1,p-Smad2/3 were also significantly raised, the protein expression levels of Smad7 was reduced; however, after being processed by alpha-lipoic(100, 200, 300 μmol/L),its CFb proliferation, secretion of collagen Ⅰ and the protein expression level of TGF-β1, p-Smad2/3 were all significantly reduced. Compared with those in the HG group,the protein expression levels of Smad7 was up-regulated. Conclusion: Alpha-lipoic suppressed the proliferation of CFs induced by high glucose, which was possibly related with the suppression of TGF-β1/Smads signal transduction pathway.
|
Received: 07 March 2013
|
|
|
|
[1]RuizOrtega M,RodriguezVita J,SanchezLopez E,et al.TGF-beta signaling in vascular fibrosis[J].Cardiovasc Res,2007,74 (2) :196-206.[2]Ramm GA, Carr SC, Bridle KR,et al. Morphology of live repair following cholestatic live injury: resolution of ductal hyperplasia, matrix deposition and regression of myofibroblasts[J]. Liver,2000, 20(5): 387-396.[3]李春君,张秋梅,于德民. α-硫辛酸减弱线粒体氧化应激保护糖尿病心肌病的机制研究[J]. 中国糖尿病杂志,2009,9(10):135-138.[4]赵晓燕,赵连友. 转化生长因子β1/Smad通路调控糜酶诱导心脏成纤维细胞胶原合成[J].中华高血压杂志,2009,17(8):743-747.[5]Bell DS. Diabetic cardiomyopathy[J].Diabetes Care,2003,26(10):2949-2951.[6]张琳, 周丽诺, 沈稚舟, 等. 成纤维细胞在糖尿病心肌纤维化病变中的作用[J].复旦学报:医学版,2002,29(5):399-402. [7]张晓敏,何继瑞.TGF-β1/ Smads 信号通路与糖尿病心肌纤维化[J].医学综述,2012,18(11):1644-1646.[8]李龙英,肖谦,高原,等. Smad3,Smad7在糖尿病大鼠心肌组织的表达[J].中国老年学杂志,2009,29(2): 132-134.[9]Tahashi Y, Matsuzaki K, Date M,et al. Differential regulation of TGF-beta signal in hepatic stellate cells between acute and chronic rat liver injury[J]. Hepatology, 2002, 35(1):49-61.[10]EulerTaimor G,Heger J.The complex pattern of Smad signaling in the cardiovascular system[J]. Cardiovasc Res,2006,69 (1):15-25.[11]Schneiders D,Heger J,Best P,et al. Smad proteins are involved in apoptosis induction in ventricular cardiomyocytes[J].Cardiovasc Res,2005,67(1): 87-96.[12]康雅萍,王国贤,魏小刚. α硫辛酸对糖尿病大鼠心肌病保护作用[J]. 中国公共卫生,2012 ,28(1):48-50. |
|
|
|