蛋白酶激活受体-2对缺血再灌注大鼠心肌细胞凋亡的影响 |
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引用本文: | 童晓红,丁家望,杨俊,刘朝奇,张艳,李松,李稳慧,李莉.蛋白酶激活受体-2对缺血再灌注大鼠心肌细胞凋亡的影响[J].中华心血管病杂志,2009,37(9). |
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作者姓名: | 童晓红 丁家望 杨俊 刘朝奇 张艳 李松 李稳慧 李莉 |
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作者单位: | 1. 三峡大学第一临床医学院宜昌市中心人民医院心内科,443003 2. 三峡大学分子生物所 |
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摘 要: | 目的 探讨蛋白酶激活受体2(PAR-2)对缺血再灌注大鼠心肌细胞凋亡的影响.方法 40只雄性SD大鼠随机分为5组:假手术组(sham组),缺血再灌注组(I/R组)和丝-亮-异亮-甘-精-亮-酰胺(SLIGRL-NH2)低剂量组(0.5 mg/kg)、中剂量组(1 mg/kg)、高剂茸组(3 mg/kg),每组8只,建立大鼠在体心肌缺血再灌注模型.采用末端标记法(TUNEL)和DNA琼脂糖凝胶电泳的方法检测心肌细胞凋亡,免疫组织化学法检测凋亡相关蛋白Bcl-2、Bax的表达,实时荧光定量PCR检测心肌细胞PAR-2mRNA的表达情况.结果 (1)SLIGRL-NH2中、高剂量组凋亡指数明显低于I/R组(SLIGRL-NH2中、高剂量组分别为23.36%±3.77%、15.56%±1.24%比I/R组35.19%±4.50%,P<0.05~0.01);凋亡相关蛋白Bcl-2高于I/R组(SLIGRL-NH2中、高剂量组分别为0.983±0.103、1.197±0.119比I/R组0.761±0.043,P<0.05~0.01);凋亡相关蛋白Bax的表达显著低于I/R组(SLIGRL-NH2中、高剂量组分别为0.646±0.041,0.578±0.029比I/R组0.759±0.035,P均<0.01);PAR-2mRNA的表达明显高于I/R组(SLIGRL-NH2中、高剂量组分别为3.73±0.45,7.62±0.81比I/R组1.42±0.41,P均<0.01).(2)DNA凝胶电泳结果显示,I/R组、SLIGRL-NH2低剂量组可见到DNA梯带,假手术组和SLIGRL-NH2中、高剂量组则无明显DNA梯带.结论 PAR-2激动剂SLIGRL-NH2可上调并激活PAR-2,并通过增加Bcl-2/Bax的比值抑制大鼠缺血再灌注心肌细胞的凋亡而发挥心肌保护效应,且该作用具有一定的剂量依赖效应.
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关 键 词: | 心肌再灌注损伤 受体 细胞凋亡 |
The effect of protense-activated receptor2 on rat apoptotic cardiomyocytes underwent ischemia reperfnsion injury |
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Abstract: | Objective To investigate the effect of protease-activated receptor2 (PAR-2) on rat apoptotic cardiomyocytes underwent iachemia reperfusion (I/R) injury. Methods Healthy male Sprague-Dawley rats were randomly divided into five groups (n = 8 each): sham-operation group, I/R (ligating the left coronary artery for 30 minutes and followed by 120 minutes reperfusion) group and three SLIGRL-NH2 groups treated with intravenous PAR-2 agonist SLIGRL-NH2 at different doses (0.5,1,3 mg/kg) 5 minutes before reperfusion. Apoptic cardiomyocytes was detected by TUNEL staining and by DNA ladder on agarose gel electrophoresis. Bax and Bcl-2 expression in myocardium was analyzed by immunohistochemical technique. The mRNA expression of PAR-2 was determined by Real-time quantitative polymerase chain reaction(RT-PCR). Results (1) The apoptosis index and the expression of Bcl-2 and Bax were significantly increased in IR group and SLIGRL-NH2 groups than those in sham group (P<0. 05~0.01). (2) Compared with I/R group, the apoptosis index and the expression of Bax were significantly reduced while the expression of Bcl-2 and PAR-2 mRNA were significantly upregnlated by SLIGRL-NH2 in a dose-dependent manner. (3) DNA Agarose gel electrophoresis demonstrated that DNA ladder existed in I/R and 0.5 mg/kg SLIGRL-NH2 group, but not in 1,3 mg/kg SLIGRL-NH2 groups. Conclusions PAR-2 agonist SLIGRL-NH2 could reduce myocardial apoptosis by upregulating the Bcl-2 and PAR-2 mRNA level and downregnlating Bax expression in a dose-dependent manner in this rat I/R model. |
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Keywords: | PAR-2 |
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