大鼠局灶性脑缺血并发多器官功能障碍综合征肺、肠Bax和Bcl-2表达变化

Changes of lung and intestinal Bax and Bcl-2 expression in rats with acute focal ischemia-reperfusion injury complicated by multiple organ dysfunction syndrome

目的研究大鼠急性局灶性脑缺血再灌注后Bax、Bcl-2在脑和肺、肠的表达变化规律,探讨急性局灶性脑缺血致多器官功能障碍综合征(MODS)的发病机制。方法采用阻断大鼠大脑中动脉后再灌注法建立大鼠局灶性脑缺血致MODS模型,将54只Wistar大鼠随机分为正常对照组(6只)、假手术组(6只)及手术组(42只),手术组又分为缺血再灌注后2、6、12、24、48、72 h及5 d 7个亚组(各6只)。应用苏木精-伊红染色观察大鼠各脏器的病理变化,免疫组织化学链霉菌抗生素蛋白过氧化酶连接法检测脑和肺、肠Bax、Bcl-2的蛋白表达,并计数阳性细胞数,计算平均阳性率(LI)。结果大鼠脑缺血后各时间点的肺、小肠组织均有不同程度的病理损害。大鼠急性脑缺血后全身炎症反应综合征(SIRS)的发生率为100.0%,MODS的发生率为57.1%;手术组大鼠大多时间点Bax和Bcl-2阳性表达明显高于正常对照组和假手术组(P值均<0.01)。结论SIRS和Bax与Bcl-2表达平衡的失调是脑缺血致MODS的可能机制。

Objective To investigate the changes of Bax and Bcl 2 expressions in the brain, lungs and in testines of rats with acute focal ischemia reperfusion injury and explore the pathogenesis of multiple organ dysfunction syndrome （MODS） in association with acute focal ischemia reperfusion. Methods Forty-two Wistar rats were subjected to middle cerebral artery occlusion （MCAO） for 2 h followed by reperfusion to establish rat models of acute focal ischemia-reperfusion injury induced MODS, and divided subsequently into 7 equal groups for observation at 2, 6, 12, 24, 48, 72 hours and 5 days after thereperfusion. Six rats with sham operation and another 6 normal rats were used as the control groups. All the rats were sacrificed at the corresponding time points for examination of the pathological changes of the organs using HE staining, and the Bax and Bcl-2 expressions in the brain, lungs and intestines were detected using immunohistochemistry with streptavidin peroxi dase, with the positive cells counted microscopically and the labeling index （LI） calculated. Results At different time points following cerebral ischemia-reperfusion, the brain, lungs, intestines of the rats all presented with pathological changes of varying severities. The incidences of-systemic inflammatory response syndrome （SIRS） and MODS were 100.0K and 57. 1% in the rats after acute focal ischemia-reperfusion, respectively. The Bax and Bcl 2 positive cells in rats with MCAO were significantly increased in the cerebral, lung, and intestinal tissues as compared with those in the normal control （P〈0.01） and sham operation group （P〈0.01）. Conclusion SIRS and the disequilibrium between Bax and Bcl-2 expression can be the possible mechanism of MODS due to acute focal ischemia reperfusioninjury. （Shanghai Med J, 2008, 31： 179-183）