异丙酚预处理对心内直视术体外循环诱导的心肌细胞凋亡的保护作用

目的 探讨异丙酚预处理对心内直视术体外循环（CPB）诱导的心肌细胞凋亡的保护作用及可能机制。方法 40例择期CPB下心内直视术患者,随机分成2组（n=20）：异丙酚预处理组（P组）和对照组（C组）。分别于CPB前、后取右心房组织行HE染色、透射电镜下观察线粒体超微结构,并检测细胞凋亡及半胱氨酸蛋白水解酶（Caspase）-9,3的表达。结果 CPB后与C组比较,P组的自动复跳率高、术后12h内多巴酚丁胺用量减少及ICU逗留时间缩短（P〈0．05）;线粒体结构较完整,嵴及内膜间隙仍清晰可见;心肌细胞凋亡数量减少,Caspase-9,3的表达降低（P〈0．05）。结论 异丙酚预处理能抑制心内直视术体外循环诱导的心肌细胞凋亡,其机制可能与保护线粒体、抑制Caspase-9、3表达有关。

Protective effects of propofol preconditioning on cardiopulmonary bypass-induced apoptosis: report of 40 cases

OBJECTIVE: To investigate the protective effects of propofol preconditioning on cardiopulmonary bypass (CPB)-induced apoptosis and its possible mechanism. METHODS: Forty patients undergoing CPB were randomly divided into 2 equal groups: propofol preconditioning group (Group P, pre-treated with propofol 2 mg/kg pre-operatively and 5 mg.kg(-1).h(-1) intra-operatively) and control group (Group C, pre-treated with midazolam 0.2 mg/kg pre- and 0.1 mg.kg(-1).h(-1) intra-operatively). Specimens of right auricle tissue were taken before and after CPB to undergo HE staining and electron microscopy to observe the changes of mitochondria. TUNEL technique was used to detect the apoptotic cells and the apoptotic index (AI) was calculated. Avidin biotin complex method was used to detect the expression of caspase-9 and caspase-3. RESULTS: The rate of spontaneous restoration of beats of Group P was 65%, significantly higher than that of Group C (30%, P < 0.05). The amount used of dobutamine within 12 h post-operatively of Group P was 4.6 +/- 1.1 microg.kg(-1).h(-1), significantly lower than that of Group C (7.8 +/- 1.0 microg.kg(-1).h(-1), P < 0.05). The ICU stay time of Group P was 40 +/- 6 h. significantly shorter than that of Group C (58 +/- 7 h, P < 0.05). The specimens taken after CPB showed that in comparison with Group C the mitochondria were relatively intact with clear ridges and intermembrane spaces in Group P. The AI after CPB of Group C was (19.3 +/- 3.5)%, significantly higher than that before CPB (7.1 +/- 1.4)%, P < 0.05] and the corresponding level of Group P (10.9 +/- 1.4)%, P < 0.05]. The expression levels of Caspace-9 and Caspace-3 after CPO of Group C were both significantly higher than those before CPB (both P < 0.05), and the corresponding levels of Group P (both P < 0.05). CONCLUSION: Propofol preconditioning significantly inhibits CPB-induced cardiomyocyte apoptosis and the mechanism is associated with protecting the mitochondria and down-regulating the expression of caspase-9 and caspases-3.