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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。
Objective: To explore whether serine has a protective effect on myocardial fibrosis and its possible mechanism. Methods: Myocardial fibrosis model was induced by continuous infusion of angiotensin Ⅱ (AngⅡ) by microinvasive pump for 28 days to observe the effect of serine on myocardial fibrosis in mice. Primary cultured rat cardiac fibroblasts were cultured alone or co-cultured with primary cardiomyocytes. Ang Ⅱ and serine were used respectively to detect the expression of collagen Ⅰ and collagen Ⅲ in cardiac fibroblasts. The effects of serine on primary cardiac muscle induced by AngⅡ Whether the expression of cytokines affect. Application of si RNA technology interferes with the glycine receptor (GlyR) in cardiomyocytes and detects whether serine inhibition of myocardial fibrosis is dependent on GlyR. Results: Masson staining suggested that prophylactic use of serine could reduce myocardial fibrosis in mice. Quantitative PCR results suggested that serine could inhibit the increase of collagen Ⅰ and Ⅲ in damaged cardiac tissues. Although serine directly inhibits the release of transforming growth factor beta and endothelin-1 from impaired cardiomyocytes, it does not directly inhibit the synthesis of collagen in cardiac fibroblasts. Serine inhibits cardiac fibroblasts only when co-cultured with cardiomyocytes Collagen I and III production increased. In addition, the protective effect of serine on the inhibition of collagen production disappears when GlyR expression is decreased in cardiomyocytes. CONCLUSIONS: Serine can indirectly inhibit cardiac fibroblasts to produce collagen through activation of glycine receptors in cardiomyocytes and decrease cardiomyocyte inflammatory response, thereby improving myocardial fibrosis.