卡维地洛对大鼠急性心肌梗死后心肌细胞凋亡和bcl-2/bax基因表达的干预作用  

Beneficial effects of carvedilol on cardiomyocyte apoptosis and bcl-2/bax expression after acute myocardial infarction an experiment with rats

作　　者：杨跃进[1] 陈跃峰[1] 阮英茆[2] 陈曦[3] 张会东[4] 田毅[5] 周燕文[5] 王清峙[2] 司文学[2] 陈纪林[1] 高润霖[1] 陈在嘉[1] 

机构地区：[1]中国医学科学院中国协和医科大学心血管病研究所阜外心血管病医院冠心病诊治,北京100037 [2]中国医学科学院中国协和医科大学心血管病研究所阜外心血管病医院病理科,北京100037 [3]中国医学科学院中国协和医科大学心血管病研究所阜外心血管病医院生化研究室,北京100037 [4]中国医学科学院中国协和医科大学心血管病研究所阜外心血管病医院实验动物科,北京100037 [5]中国医学科学院中国协和医科大学心血管病研究所阜外心血管病医院实验外科,北京100037

出　　处：《中华医学杂志》2006年第13期919-922,共4页National Medical Journal of China

摘　　要：目的评价新一代β受体阻断剂卡维地洛对大鼠急性心肌梗死(AM I)后心肌细胞凋亡及其相关基因表达的干预作用。方法将冠状动脉结扎术后24 h存活的雌性SD大鼠(83只)分为AM I对照(M I组,43只)和卡维地洛(10 mg.kg-1.d-1)治疗组(C组,40只),另设假手术组(S组,27只)。各组再按观察时点分为48 h和4周两个亚组。C组于术后24 h直接灌胃法给药。用TUNEL法和DNA凝胶电泳检测心肌细胞凋亡。用免疫组化方法和W estern印迹法检测“抑制凋亡复合基因”bc l-2/bax的表达。结果(1)M I组梗死/瘢痕区、梗死边缘区和非梗死区的心肌细胞凋亡指数(48 h 21.2%±15.6%、19.8%±12.0%和6.3%±4.5%;4周23.5%±13.0%、8.0%±4.4%和3.2%±1.6%)高于假手术组(48 h 1.3%±1.1%,4周1.2%±0.3%,均P<0.05);凋亡促进基因bax的表达M I48 h组明显高于假手术组,但“凋亡抑制基因”bc l-2仅在M I48 h组梗死区心肌细胞中表达增加;bc l-2/bax的比值M I48 h组(1.06)低于假手术组(1.87)。(2)C48 h组3个区域的心肌细胞凋亡指数与M I组比较,差异无统计学意义(均P>0.05),但梗死区及边缘区bc l-2的表达均增加;C4周组梗死/瘢痕区及边缘区的心肌细胞凋亡指数(4.0%±2.0%,2.9%±1.6%)均低于M I组(23.5%±13.0%,8.0%±4.4%,均P<0.05),且瘢痕区心肌细胞中bax的表达亦明显降低,但bc l-2的表达均无明显变化;C组大鼠48 h和4周时的心肌细胞bc l-2/bax的比值(1.72,2.23)高于M I组(1.06,1.8),与假手术组(1.87,2.25)相当。结论大鼠出现AM I后,长时间(4周)用卡维地洛治疗能有效防止梗死/瘢痕区及其边缘区心肌细胞凋亡的发生,并使bc l-2/bax的比值增加。Objective To investigate the beneficial effects of carvedilol on cardiomyocyte apoptosis and related gene expression after acute myocardial infarction （AMI）. Methods Eighty-three female SD rats underwent ligation of left anterior descending coronary artery, and were randomly assigned to 2 groups 24 hours later： carvedilol（n =40, 10 mg · kg^-1 · d^-1was administered via direct gastric gavage 24 hs after the ]igation, Group C）and AMI control group （n = 43, normal saline of the same volume was given by gastric gavage, Group MI）. Another 27 rats were used as sham operation group （ Group S, administered with normal saline too）. The rats of each group were killed and their hearts were taken out 48 hours and 4 weeks after observation respectively （MI-48 h, MI-4 week, C-48 h, C-4 week, S-48 h, and S-4 week subgroups）. TUNEL and DNA gel electrophoresis were used to detect the cardiomyocyte apoptosis. Immunohistochemistry and Western blotting were used to detect the expression of bcl-2 and bax. Results The apoptotic indices of the infracted/scar, border and non-infarcted areas at any time-point of Group MI were all significantly higher than those of Group S （ all P 〈0.05）. Only the apoptotic indices of the infracted/scar and border areas of the C-4 week subgroup were significantly lower than those of the MI-4 week subgroup （ beth P 〈 0.05 ）, and were close to those of the non-infarcted area. DNA gel electrophoresis showed that the positive rate of Group S at any time-point were both 0, the positive rate of MI-48 h subgroup and C-48 h subgroup were both significantly higher than that of Group S （ both P 〈 0.05 ） without significant difference between these 2 groups, and the positive rates of the MI-4 week subgroup and C-4 week subgroup were both 0. Immunohistochemistry showed that the hax gene expression was slightly to significantly increased in the infarcted/scar, border, and non-infarcted areas of the MI-48 h and MI-4 week subgroups. The bcl-2 expression was significantly increas

关 键 词：肾上腺素能Β受体拮抗剂 心肌梗塞 脱噬作用 癌基因 大鼠 

分 类 号：R542.22[医药卫生—心血管疾病]