Bcl-2和p 53蛋白表达在脓毒症大鼠心肌细胞凋亡中的作用研究  

Study of the effect of p53 and Bcl-2 protein expression in myocardial apoptosis in septic rats

作　　者：翟诚顺[1] 唐皓[1] 梁艳冰[1] 陈志斌[1] 李振宇[1] 马中富[1] 

机构地区：[1]中山大学附属第一医院酱内科,广东广州,510080

出　　处：《中华危重病急救医学》2008年第12期-,共5页Chinese Critical Care Medicine

基　　金：广东省科技计划，广东省广州市科委重点课题

摘　　要：目的 探讨Bcl-2和p53基因在脓毒症大鼠心肌细胞凋亡中的作用.方法 将成年雄性SD大鼠随机分为正常对照组(n=6)、假手术组(n=6)、模型组(n=24).以盲肠结扎穿孔术(CLP)复制脓毒症大鼠模型.术后3、9、12和24 h各取6只大鼠的心肌组织备检.以电镜和原位末端缺刻标记法(TUNEL)检测心肌细胞凋亡变化;用免疫组化法检测Bcl-2和p53的蛋白表达.结果 模型组大鼠心肌细胞凋亡指数(AI)随时间延长明显升高,于12 h达峰值C(55.633±2.073)%),24 hC(33.683±2.070)%]较12 h明显下降,但各时间点均明显高于正常对照组[(1.500±0.141)%]和假手术组[(1.567±0.258)%],差异均有统计学意义(P均<0.05).模型组各时间点p53基因的蛋白表达阳性数[3 h最低为(13.817±0.964)%.12 h峰值为(80.567±5.055)%]均较正常对照组C(0.617±0.232)%]和假手术组C(0.600±0.297)%)明显升高(P均<0.05),其变化与TUNEL检测凋亡的结果一致;而Bcl-2基因的蛋白表达阳性数C3 h最高为(31.650±1.799)%,12 h最低为(0.650±0.308)%]均较正常对照组[(47.017±0.691)%]和假手术组[(46.817±0.567)%]明显降低(P均<0.05),其变化与TUNEL检测凋亡的结果趋势相反.结论 细胞凋亡可能是脓毒症心肌损害的机制之一,其调控基因p53和Bcl-2基因的改变或许可以作为脓毒症病情改变的标志,对其进行干预,以改善脓毒症的预后.Objective To explore the significance of p53 and Bcl-2 gene in myocardial apoptosis in septic rats. Methods Adult male Sprague-Dawley (SD) rats were randomly divided into normal control group (n= 6), sham operation group (n=6) and cecal ligation and puncture (CLP) group (n= 24). The sepsis model was reproduced by CLP. Rats in CLP group were divided into four subgroups according to the time points of 3, 9, 12, and 24 hours after operation, with 6 rats in each subgroup; and their hearts were examined according to the experimental protocal. Myocardial apoptosis was detected with electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) technique. Bcl-2 and p53 protein expression was measured by immunohistochemistry method. Results Myocardial apoptosis index (AI) in septic rats were increased, higher than that in normal contral group [(1. 500±0. 141)%] and sham operation group [(1. 567±0. 258)%, all P<0. 05]. The myocardial AI peaked at 12 hours [(55.633 ±2. 073)%], and lowered at 24 hours [(33. 683±2. 070)%]. The expression level of p53 protein in CLP group was lowest at 3 hours [(13. 817±0. 964)%], peaked at 12 hours [(80. 567±5. 055)%], and higher than that in normal control group [(0. 617±0. 232)%] and sham operation group [(0. 600±0. 297)%, all P<0. 05]. The trend was parallel with that of the results of TUNEL. However, the expression level of Bcl-2 protein peaked at 3 hours [(31. 650±1. 799)], and was lowest at 12 hours [(0. 650±0. 308)%], and lower than that in normal control group [(47. 017 ± 0. 691)%] and sham operation group [(46. 817 4±0. 567)%, all P<0. 05]. The trend was opposite with that of the results ot TUNEL. Conclusion Myocardial apoptosis may be a mechanism of the pathogenesis of myocardial injury in sepsis. The change in the modulating genes p53 and Bcl-2 of apoptosis may serve as indicators of myocardial injury, p53 and Bcl-2 gene may be used as an interventional means in sepsis to change its outcome.

关 键 词：脓毒症 凋亡 心肌损害 P53 BCL-2 

分 类 号：R686[医药卫生—骨科学]