δ阿片受体激动剂对脓毒症大鼠肺组织细胞凋亡及肺组织Bcl-2、Caspase-3表达的影响

Effect of δ-opioid Receptor Agonists on Apoptosis of Pulmonary Tissue and Expression of Bcl-2 and Caspase-3 in Septic Rat

目的:观察δ阿片受体激动剂DADLE对脓毒症大鼠肺组织细胞凋亡及肺组织Bcl-2、Caspase-3表达的影响。方法:采用盲肠结扎加穿孔(CLP)法制作大鼠脓毒症模型,SD大鼠54只随机分为CLP组、DADLE组和假手术(SHAM)组。在不同时间点(12h、36h、72h)处死大鼠,原位末端标记检测肺组织细胞凋亡情况,免疫组化法检测肺组织中Bcl-2、Caspase-3蛋白表达的动态变化并比较肺组织的病理改变。结果:CLP组大鼠肺组织病理损害较SHAM组明显加重,DADLE组肺组织的病理变化明显减轻;CLP组大鼠肺组织细胞凋亡指数较SHAM组明显升高(P<0.01),以36h组最明显(P<0.01)。结论:DADLE明显改善脓毒症大鼠肺组织的病理变化,可能与DADLE下调Caspase-3表达、上调Bcl-2表达,从而抑制肺组织细胞凋亡有关。

Objective To observe the effects ofδ-opioid receptor agonists DADLE on apoptosis of pulmonary tissue and expression of Bcl-2 and Caspase-3 in septic rat. Methods Sepsis was reproduced in rats by cecum ligation and puncture （CLP）. Fifty-four SD rats were randomly divided into CLP group, DADLE group and sham-operation （SHAM） group. The rats were respectively killed at different time （12 h, 36 h and 72 h after operation）. Pneumonocyte apoptosis was detected by TdT-mediated dUTP Nick End Labeling （TUNEL）. The expressions of Bcl-2 and Caspase-3 protein were detected by immunohistochemistry. Results The pathologic changes in pathological lesin of rats in CLP group were obviously more seriously as compared with SHAM group, while it was improved obviously in DADLE group. The apoptosis index of rat pneumonocytes in CLP group significantly increased as compared with SHAM group （P 0.01）, and it was further prominent at 36h （P 0.01）. Conclusion The findings indicate that δ-opioid receptor agonists DADLE can obviously improve pulmonary tissue pathological changes of septic rats, with the protective mechanism of downregulatiion of Caspase-3 expression and upregulation of Bcl-2 expression ,and thus to repress the apoptosis of pulmonary tissue.