PI3K／Akt信号转导通路在乌司他丁后处理减轻CPB下心脏瓣膜置换术患者心肌细胞凋亡中的作用

Role of PI3K/Akt signal pathway in ulinastatin postconditioning-induced attenuation of apoptosis in myocardial cells in patients undergoing cardiac valve replacement with cardiopulmonary bypass

目的探讨磷脂酰肌醇3．激酶（P13K）／丝氨酸．苏氨酸蛋白激酶（Akt）信号转导通路在乌司他丁后处理减轻CPB下心脏瓣膜置换术患者心肌细胞凋亡中的作用。方法择期CPB下心脏瓣膜置换术患者40例，性别不限，年龄21～59岁，心功能和ASA分级Ⅱ或Ⅲ级。采用随机数字表法，将患者分为2组（n=20）：生理盐水对照组（c组）和乌司他丁后处理组（U组）。u组于主动脉开放前5min经主动脉根部灌注乌司他丁4000～5000U·kg^-1·min^-1（剂量1万U／kg）；C组给予等容量生理盐水。于升动脉开放后45min时取右心耳心肌组织，检测Akt、磷酸化Akt（p-Akt）与细胞色素c、caspase-9、Bcl-2、Bax表达和细胞凋亡情况，并计算Bcl-2与Bax表达的比值（Bcl．2／Bax）和凋亡指数（AI）。结果与C组比较，u组心肌组织p-Akt与Bcl-2表达上调，心肌组织细胞色素c、caspase-9及Bax表达下调，Bcl-2／Bax升高，AI降低（P〈O．05）。结论乌司他丁后处理通过激活P13K／Akt信号转导通路减轻CPB下心脏瓣膜置换术患者心肌细胞凋亡。

Objective To investigate the role of phosphatidylinositol 3-kinase （PI3K）/protein-serine-thre- onine kinases （Akt） signal pathway in ulinastatin posteonditioning-induced attenuation of apoptosis in myocardial cells in patients undergoing cardiac valve replacement with eardiopulmonary bypass （CPB）. Methods Forty NY- HA class and ASA physical status 11 or m patients of both sexes, aged 21-59 yr, scheduled for cardiac valve replacement with CPB, were randomly divided into 2 groups （ n = 20 each） ： normal saline control group （group C） and ulinastatin postconditioning group （group U）. In group U, ulinastatin 10 000 U/kg was perfused via the aortic root at 4000-5000 U＂ kg- 1. min- l starting from 5 min before aortic unclamping. In group C, the equal volume of normal saline was given instead of ulinastatin. Myocardial specimens were taken from the right auricle at 45 min af- ter aortic unclamping for determination of the expression of Akt, phosphorylated Akt （p-Akt）, cytochrome e, caspase-9, Bcl-2 and Bax, and cell apoptosis. Bcl-2/Bax ratio and apoptotic index were calculated. Results The expression of p-Akt and Bcl-2 and Bcl-2/Bax ratio were significantly higher, and the expression of cytochrome e, caspase-9 and Bax and apoptotic index were lower in group U than in group C （ P 〈0. 05 ）. Conclusion Ulinastatin postconditioning attenuates apoptosis in myocardial cells in patients undergoing cardiac valve replacement with CPB through activating PI3K/Akt signal pathway.