ALK7在高糖诱导的心肌成纤维细胞转化及Ⅰ型胶原合成中的作用  

Role of ALK7 in the transformation of cardiac fibroblasts and the production of collagen type I induced by high glucose

作　　者：商睿[1,2] 唐梦熊[2,3] 刘琳[1,2] 丁文渊[2,3] 郝盼盼[2,3] 陈玉国[2,3] 

机构地区：[1]山东大学医学院,济南250012 [2]山东大学齐鲁医院急诊科,济南250012 [3]山东大学教育部和卫生部心血管重构和功能研究重点实验室,济南250012

出　　处：《山东大学学报（医学版）》2013年第8期1-6,48,共7页Journal of Shandong University:Health Sciences

基　　金：国家自然科学基金(81070192);山东省优秀中青年科学家科研奖励基金(BS2011YY013);山东大学自主创新基金(2009TS069)

摘　　要：目的研究高糖诱导的心肌间质纤维化(心肌成纤维细胞表型转化以及胶原分泌)过程中活化素受体样激酶7(ALK7)的作用。方法体外高糖培养大鼠心肌成纤维细胞,免疫荧光法观察成纤维细胞表型转化,real time-PCR法检测心肌成纤维细胞ALK7和Ⅰ型前胶原mRNA的表达水平,ELISA法检测心肌成纤维细胞分泌Ⅰ型胶原水平,Western-blotting法测定心肌成纤维细胞ALK7蛋白的表达水平;siRNA抑制ALK7表达,再次观察高糖对心肌成纤维细胞表型转化及上述各因子表达的影响。结果高糖刺激心肌成纤维细胞转化为肌成纤维细胞;高糖促进Ⅰ型胶原mRNA和蛋白的表达(P<0.05);高糖促进成纤维细胞ALK7 mRNA和蛋白的表达(P<0.05);ALK7 siRNA抑制ALK7的表达后,高糖促进心肌成纤维细胞转化及合成Ⅰ型胶原的作用下降(P<0.05)。结论 ALK7参与了高糖诱导的心肌成纤维细胞表型转化及合成Ⅰ型胶原的代谢过程。Objective To investigate the role of ALK7 in the process of myocardial interstitial fibrosis （ transformation of cardiac fibroblasts and the production of collagen type I by cardiac fibroblasts） induced by high glucose. Methods Neonatal rat cardiac fibroblasts were cultured in vitro with different concentrations of glucose. Fibroblast phenotype transformation was observed by immumofluorescence method. The mRNA expressions of collagen type I and ALK7 were measured by real time-PCR ; the protein level of collagen type I was determined by enzyme-linked immunosorbent assay ; the protein level of ALK7 was measured by Western-blotting analysis. Thereafter, we investigated the theraputic effects of ALK7 siRNA on the above changes induced by high glucose. Results The transformation of cardiac fibro- blasts to myofibroblast increased by high glucose; Both mRNA mad protein expressions of collagen type I increased after high glucose stimulation （ P 〈 0.05 ） ; The mRNA and protein expressions of ALK7 increased by high glucose （ P 〈 0.05 ） ; The increased mRNA and protein levels of collagen type I and the transformation of cardiac fibroblasts inducedby high glucose were reversed by treatment with ALK7 siRNA （P 〈 0.05 ）. Conclusion ALK7 is involved in the transformation of cardiac fibroblasts to myofibroblast and the production of collagen type I by cardiac fibroblasts induced by high glucose.

关 键 词：高糖 心肌成纤维细胞 肌成纤维细胞 Ⅰ型胶原 ALK7 

分 类 号：R542.2[医药卫生—心血管疾病] R322[医药卫生—内科学]