甘氨酸受体在甘氨酸抗心肌细胞缺氧/复氧损伤中的作用机制研究

目的：探讨甘氨酸受体在心脏保护中的作用及甘氨酸受体的性质。方法：利用原代培养的SD大鼠乳鼠心肌细胞建立心肌缺氧/复氧(A/R)模型，并用甘氨酸受体阻断法和消除细胞外氯离子法, 测定各组培养心肌细胞内超氧化物歧化酶（SOD）活性、丙二醛（MDA）及一氧化氮（NO）的含量、钙离子浓度和心肌细胞凋亡率。结果：A/R组用甘氨酸处理后SOD活性、NO含量升高，MDA含量、［Ca²⁺］_i、细胞凋亡率降低，与A/R组比较显著差异。分别用甘氨酸受体阻断剂士的宁和消除细胞外氯离子处理后，甘氨酸的上述保护作用明显减弱，与A/R组比较无显著差异。结论：甘氨酸能抑制缺氧/复氧乳鼠心肌细胞的自由基生成、抑制钙超载，减轻心肌细胞的凋亡并增加细胞内SOD等保护蛋白和NO的合成而发挥细胞保护作用。甘氨酸的细胞保护作用可能是通过甘氨酸受体发挥作用的，甘氨酸受体的本质可能是甘氨酸门控氯离子通道。

Role of glycine receptor in protection of glycine against anoxia/reoxygenation injury in cardiomyocytes

AIM: To investigate whether glycine receptor is involved in the protection of glycine against(anoxia/reoxygenation) injury in cardiomyocytes by detecting oxygen free radical metabolism,apoptosis and intracellular calcium overload.METHODS: The neonatal rat cardiomyocytes were cultured and exposed to anoxia and reoxygenation((A/R)) in the presence of glycine receptor antagonist,glycine or in free chloride buffer.The superoxide dismutase(SOD) activity,the contents of malondialdehyde(MDA) and nitric oxide(NO),the intracellular free calcium concentration and the apoptotic rate in the cardiomyocytes were determined.RESULTS: SOD activity and NO content in cardiomyocytes were lower,but MDA content,intracellular free calcium concentration and apoptotic rate in cardiomyocytes were higher in A/R group than those in control.Pretreatment with glycine inhibited the above changes caused by A/R,which was reversed by strychnine treatment and in the free chloride medium.CONCLUSIONS: Glycine inhibits free radical production,attenuates calcium overload,decreases apoptotic rate and increases SOD activity and NO release in cardiomyocytes exposed to(A/R).These findings suggest that glycine exerts a protective effect against A/R injury via glycine receptor and glycine protects the neonatal rat cardiomycytes from A/R-induced injury in a chloride-dependent manner.