硫化氢通过下调葡萄糖调节蛋白78参与大鼠急性心肌缺血保护

Protective Effects of Hydrogen Sulfide in Rats with Acute Myocardial Ischemia by Down-tegulating of Glucose Regulated Protein 78(GRP78)

目的探讨硫化氢(hydrogen sulfide,H2S)是否通过改变葡萄糖调节蛋白78(glucose regulated protein 78,GRP78)的表达参与大鼠急性心肌缺血保护。方法 36只雄性SD大鼠随机分为:正常对照组、心肌缺血4、8、12、24h组和H2S组,每组6只。心肌缺血模型采用皮下多点注射10mg/kg的异丙肾上腺素(isoprinosine hydrochloride,ISO)。H2S组于缺血24h后腹腔注射5.6μmol/kg的H2S供体NaHS,取材前15min再次给予等剂量NaHS,余各组注射等剂量生理盐水。造模后检测血清学指标、心电图及病理组织学变化,确定心肌缺血模型是否建立成功;采用反转录-聚合酶链反应(RT-PCR)和实时荧光定量PCR(real time-PCR)分别对各组心肌GRP78 mRNA的表达进行定性和相对定量分析。结果与正常组比较,缺血模型组心肌组织中GRP78mRNA的表达显著上调。与缺血24h组比较,H2S组GRP78 mRNA的表达显著下调。结论 H2S保护心肌缺血的效应可能部分通过下调GRP78产生作用。

Objective To investigate whether protective effects of hydrogen sulfide（H2S） in the myocardial ischemia injury are mediated by alteration of the expression of GRP78 in rats.Methods Thirty-six SD rats were randomized into control group,myocardial ischemia group（4,8,12 and 24h） and H2S administration group.Myocardial ischemia was induced by subcutaneous injection of isoprinosine hydrochloride through multisite and multipath way protocol.NaHS（5.6μmol/kg）,the donor of H2S,was intraperitoneal injected after 24h of ischemia and 15min before drawing the materials.The electrocardiogram,myocardial enzymes and histological changes were detected to define the myocardial ischemia.The GRP78 mRNA expression was detected by RT-PCR and real time-PCR in myocardium.Results The expression of GRP78 was significantly increased in myocardial ischemia groups than that in control group.H2S significantly decreased the expression of GRP78 mRNA in myocardial ischemia 24h group.Conclusion H2S produces probably protective effects in myocardial ischemia injury which is partly mediated by decreasing of the expression of GRP78.