文章摘要
陈世超,储 鑫,蒋云龙,周文颖,袁 越,杨 青,李晓宇,陈 琪.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[J].南京医科大学学报,2017,(7):792~798
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
投稿时间:2017-03-03  
DOI:10.7655/NYDXBNS20170702
中文关键词: 丝氨酸  Ang Ⅱ  甘氨酸受体  心肌纤维化
英文关键词: serine  angiotensin Ⅱ  GlyR  myocardial fibrosis
基金项目: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)
作者单位
陈世超 南京医科大学病理生理学系江苏 南京 211166 
储 鑫 南京医科大学病理生理学系江苏 南京 211166 
蒋云龙 南京医科大学病理生理学系江苏 南京 211166 
周文颖 南京医科大学病理生理学系江苏 南京 211166 
袁 越 南京医科大学病理生理学系江苏 南京 211166 
杨 青 南京医科大学病理生理学系江苏 南京 211166 
李晓宇 南京医科大学病理生理学系江苏 南京 211166 
陈 琪 南京医科大学病理生理学系江苏 南京 211166 
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中文摘要:
      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(angiotensin Ⅱ,Ang Ⅱ)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Ang Ⅱ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Ang Ⅱ诱导的原代心肌细胞炎症因子表达有无影响。应用siRNA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。
英文摘要:
      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 cardiomyocytes 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 cardiomyocyte. Results: In the presence of cardiomyocyte, production of collagen Ⅰ and 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 cardiomyocyte.
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