摘要
目的探讨参附注射液(SFI)对大鼠心肌缺血再灌注时第10染色体同源丢失性磷酸酶-张力蛋白酶基因(PTEN)及磷脂酰肌醇-3激酶(PI3K)表达的影响。方法健康雄性SD大鼠30只,随机分为三组:假手术组(Sham组)、缺血再灌注组(I/R组)和SFI治疗组。Sham组丝线穿过冠状动脉前降支但不结扎;I/R、SFI组通过结扎冠状动脉左前降支30min,再灌注120min的方式制备心肌缺血再灌注损伤模型。缺血前30min,SFI组经腹腔注射参附注射液10ml/kg,Sham组和I/R组均腹腔注射等量生理盐水。于再灌注120min时处死大鼠,取左心室心肌组织,计算心肌梗死面积。以缺口末端标记(TUNEL)法检测心肌细胞凋亡情况,计算细胞凋亡指数。免疫组织化学法测定心肌组织PTEN和PI3K表达水平,并计算其比值(PTEN/PI3K)。观察心肌组织病理学损伤程度。细胞凋亡指数与PTEN/PI3K行直线相关分析。结果与Sham组比较,I/R组和SFI组心肌梗死面积增加,细胞凋亡指数升高,PTEN和PI3K表达均上调(P<0.05),SFI组PTEN/PI3K降低(P<0.05);与I/R组比较,SFI组心肌梗死面积减小,细胞凋亡指数降低,PTEN表达下调,PI3K表达上调,PTEN/PI3K降低(P<0.05);SFI组心肌损伤程度较I/R组减轻。I/R组及SFI组细胞凋亡指数与PTEN/PI3K均呈正相关(分别为r=0.788、P=0.007和r=0.829、P=0.003)。结论 SFI能够抑制心肌细胞凋亡,减轻大鼠心肌缺血再灌注损伤,其作用机制与下调心肌组织PTEN表达,上调PI3K表达有关。
Objective To investigate the effect of Shenfu injection(SFI)on the expression of phosphatase and tensin homolog deleted on chromosome 10(PTEN)and phosphatidylinositol 3-kinase(PI3K)during myocardial ischemia-reperfusion(I/R)injury in rats.Methods Thirty adult male SD rats weighing 220-280 g were randomly divided into three groups(n=10,each):group I sham-operation group(Sham);group II ischemia and reperfusion group(I/R);group III,Shenfu injection group(SFI).In Sham group,the anterior descending branch of left coronary artery was exposed but not occluded.The ischemia and reperfusion injury models in I/R and SFI groups were made by temporary ligation of the anterior descending branch of left coronary artery,ischemia lasted for 30 min and reperfusion for 120 min.In SFI group,the Shenfu injection(10 ml/kg) was intraperitoneally injected 30 min before ischemia.In Sham and I/R group,normal saline(10 ml/kg) was intraperitoneally injected.The rats were killed and their hearts were removed at 120 min of reperfusion for histopathological examination and determination of apoptotic myocardium cells by TUNEL method.Expression of PTEN and PI3K were detected by immunohistochemical method.PTEN/PI3K ratio,myocardial infarct size of left ventricle and apoptosis index were calculated.Correlation between apoptosis index and PTEN/PI3K ratio was analyzed.Results Compared with the sham group,myocardial infarct size,apoptosis index and expression of PTEN and PI3K in I/R group and SFI group were significantly increased in myocardium with ischemia-reperfusion(P<0.05).PTEN/PI3K ratio was significantly decreased in SFI group as compared with sham group(P<0.05).Myocardial infarct size and apoptosis index were significantly decreased,PTEN expression was down-regulated,PI3K expression was up-regulated and PTEN/PI3K ratio was significantly decreased in SFI group as compared with I/R group(P<0.05).Myocardial pathological damage was attenuated in SFI group than I/R group.Apoptosis index was positively correlated to PTEN/PI3K ratio(r=0.788,P=0.007
出处
《中华临床医师杂志(电子版)》
CAS
2011年第10期2900-2905,共6页
Chinese Journal of Clinicians(Electronic Edition)
基金
"135"重点人才资助项目(303070534EF02)