摘要
目的从分子水平探讨纳洛酮对急性心肌缺血再灌注细胞凋亡和凋亡相关基因bcl-2产物Bcl-2蛋白表达的影响,及其对心肌的保护作用。方法SD大鼠30只,随机分成3组,单纯缺血再灌注组,纳洛酮干预组(缺血前10min及再灌注2h后腹腔注射纳洛酮0.517mg/kg)和正常对照组,每组10只。实验动物采用戊巴比妥钠(40mg/kg)腹腔注射麻醉,开胸,打开心包,穿线结扎左冠状动脉前降支再恢复灌注制备大鼠心肌缺血再灌注模型。用免疫组化法检测心肌组织Bcl2蛋白表达;用放射免疫法测定血清中肿瘤坏死因子-α(TNF-α)的含量。结果正常对照组无Bcl-2蛋白表达,TNF-α含量为(0.39±0.06)μg/L;单纯缺血再灌注组Bcl2蛋白表达及TNF-α含量均增加。与单纯缺血再灌注组比较,纳洛酮干预组Bcl-2蛋白表达明显增加(+++vs.+);TN-Fα含量明显降低〔(0.55±0.12)μg/L比(0.86±0.11)μg/L,P<0.01)。结论纳洛酮预处理可抑制TNF-α的产生,并通过上调Bcl2蛋白表达,抑制缺血再灌注后心肌细胞的凋亡,从而保护缺血再灌注对心肌细胞的损伤。
ObjectiveTo investigate the effect of naloxone on myocardial cell apoptosis and apoptosis- related gene Bcl-2 in rats with acute myocardial ischemia/ reperfusion (AMIR) injury, and explore the mechanism of protective effect of naloxone on myocardium. Methods Thirty SD rats were randomly divided into three groups (n=10): ischemia/reperfusion group, naloxone preconditioning group (naloxone was injected intraperitoneally 10 minutes before ischemia and 2 hours after reperfusion), and normal control group. The left anterior descending branch (LAD) of rat coronary artery was tied and untied in ischemia/reperfusion group and naloxone preconditioning group to establish the AMIR model in rats. The animals were then sacrificed and hearts were harvested .The expression of Bcl-2 protein was observed by immunohistochemical technique. Radioimmunoassay (RIA) was used to determine tumor necrosis factor -α (TNF-α) in serum. Results In the normal control group, there was no Bcl-2 expression and TNF-α level was (0.39±0.06)μg/L. Higher expression of Bcl-2 and increased TNF-α levels were found in ischemia/reperfusion group. The expression of Bcl-2 protein increased significantly 〔(+++) vs.(+)〕, and TNF-α was significantly lower in naloxone preconditioning group than those in the normal control group 〔(0.55±0.12)μg/L vs. (0.86±0.11)μg/L,P<0.01〕. Conclusion Naloxone can protect myocardium from AMIR injury by inhibiting the apoptosis of cardiomyocytes induced by TNF-α and up-regulating protein expression of bcl-2 gene.
出处
《中国危重病急救医学》
CAS
CSCD
北大核心
2005年第7期430-432,i001,共4页
Chinese Critical Care Medicine
基金
甘肃省自然科学基金资助项目(YS-022-A23-26)
