丝氨酸通过甘氨酸受体缓解血管紧张素Ⅱ诱导的心肌纤维化  

Serine ameliorates myocardial fibrosis induced by AngⅡ through glycine receptor

作　　者：陈世超[1] 储鑫[1] 蒋云龙[1] 周文颖[1] 袁越[1] 杨青[1] 李晓宇[1] 陈琪[1] 

机构地区：[1]南京医科大学病理生理学系,江苏南京211166

出　　处：《南京医科大学学报（自然科学版）》2017年第7期792-798,共7页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金(81230070;91339202;81670263);江苏省高校自然科学研究重大项目(15KJA310001);江苏省大学生创新创业训练计划基金资助项目(2014103120212)

摘　　要：目的:探索丝氨酸是否对心肌纤维化具有保护作用及其可能的机制。方法:通过微渗透泵持续给予血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)28 d建立小鼠心肌纤维化模型,观察丝氨酸对小鼠心肌纤维化的效应。乳大鼠原代心脏成纤维细胞单独培养或与原代心肌细胞共培养,分别用AngⅡ和丝氨酸处理,检测心脏成纤维细胞胶原Ⅰ和胶原Ⅲ的表达;并检测丝氨酸对AngⅡ诱导的原代心肌细胞炎症因子表达有无影响。应用si RNA技术干扰心肌细胞甘氨酸受体(glycine receptor,GlyR),并检测丝氨酸抑制心肌纤维化是否依赖GlyR。结果:Masson染色提示,预防性使用丝氨酸可以减轻小鼠心肌纤维化;定量PCR结果提示丝氨酸可以抑制受损心脏组织中胶原Ⅰ和Ⅲ增多。虽然丝氨酸能直接抑制受损心肌细胞转化生长因子β和内皮素-1释放,但它并不能直接抑制心脏成纤维细胞合成胶原增多,只有与心肌细胞共培养时,丝氨酸才能抑制心脏成纤维细胞的胶原Ⅰ和Ⅲ产生增多。此外,当心肌细胞的GlyR表达降低后,丝氨酸抑制胶原生成的保护效应随之消失。结论:丝氨酸可通过激活心肌细胞甘氨酸受体,减少心肌细胞炎症反应,间接抑制心脏成纤维细胞产生胶原,进而改善心肌纤维化。Objectives： To explore whether serine can protect myocardial fibrosis as a ligand of glycine receptor （GlyR）. Methods： Serine or saline were injected intraperitoneally to mice a week before angiotensin Ⅱ （Ang Ⅱ ） administrated by using an osmotic pump, and the myocardial fibrotic status in mice was detected 28 days later. The expression levels of inflammatory markers in car- diomyocytes response to angiotensin Ⅱ （Ang Ⅱ ） were detected with or without serine in vitro. Primary cardiac fibroblast cells were isolated from neonatal rat and treated with Ang Ⅱ or serine,respectively,and then the expression levels of collagen Ⅰ and collagen Ⅲ were checked by quantitative PCR. The expression levels of collagen Ⅰ collagen Ⅲ were checked in both cardiac fibroblasts and cardiomyocytes co-cultured system, mRNA levels of collagen Ⅰ and Ⅲ were checked after GlyR knocked down by siRNA transfection in eardiomyoeyte. Results： In the presence of cardiomyocyte, production of collagen Ⅰand collagen Ⅲ was enhanced in cardiac fibroblasts after Ang Ⅱ treatment, however,the enhancement is inhibited by serine. Importantly, the protective of serine on cardiac fibrosis was abolished by GlyR knockdown. Conclusion： Serine could blunt myocardial fibrosis through GlyR in eardiomyoeyte.

关 键 词：丝氨酸 AngⅡ 甘氨酸受体 心肌纤维化 

分 类 号：R542.2[医药卫生—心血管疾病]