血红素加氧酶-1对大鼠体外循环后肺组织抗细胞凋亡的研究  

Anti-apoptosis effect and mechanism of heme oxygenase-1 on lung injury after cardiopulmonary bypass

作　　者：生伟[1] 王海桃[2] 池一凡[1] 孙龙[1] 牛兆倬[1] 林明山[1] 乔友进[1] 吴建涛[1] 

机构地区：[1]青岛大学附属青岛市市立医院心脏外科,山东青岛266071 [2]青岛市肿瘤医院药学部,山东青岛266042

出　　处：《中国胸心血管外科临床杂志》2017年第5期384-389,共6页Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

基　　金：青岛市卫计委课题(2013-WSZD012)

摘　　要：目的观察钴原卟啉(Co PP)诱导肺组织血红素加氧酶-1(HO-1)表达在大鼠体外循环(CPB)后肺组织损伤中的抗细胞凋亡作用,并对其作用机制进行分析。方法将144只雄性Wistar大鼠(体重250~350 g)随机分为3组,每组48只:A组(对照组)、B组(Co PP组)、C组[Co PP+锌原卟啉(Zn PP)组]。建立改良大鼠CPB肺损伤模型。制模成功后采用断颈法分别于CPB前(T0)、CPB结束即刻(T1)、CPB后2 h(T2)、6 h(T3)、12 h(T4)、24 h(T5)将大鼠处死。取肺组织检测相应的指标,免疫组化方法测定血红素加氧酶-1(HO-1)和B细胞淋巴瘤-2(Bcl-2)蛋白的表达以及TUNEL细胞凋亡检测试剂盒检测细胞凋亡。结果 B组大鼠肺组织中HO-1蛋白表达在CPB开始前后均有明显增加,其活性测定结果与蛋白表达结果一致,在各时间点均强于A组和C组(P<0.05)。各组大鼠肺组织细胞Bcl-2蛋白表达在CPB前无明显差异(P>0.05),在CPB后表达逐渐下调,B组在CPB后各时间点均高于A组和C组(P<0.05)。各组大鼠肺组织细胞凋亡指数(AI)在CPB前无显著差异,B组在CPB后各时间点均低于A组和C组(P<0.05)。HE染色显示B组肺组织损伤程度较A组和C组明显减轻。结论 Co PP可以诱导肺组织HO-1的高表达,而且经过CPB后,仍保持较高的表达。内源性HO-1高表达在体外循环肺损伤中具有一定的抗细胞凋亡作用。其抗凋亡作用可能通过使抗凋亡蛋白Bcl-2蛋白增高而实现的。Objective To determine the anti-apoptosis effects of heme oxygenase-1 （HO-1） on lung injury after cardiopulmonary bypass （CPB）, and to investigate its probable mechanisms. Methods A total of 144 male Wistar rats with wight of 250-350 g were divided into 3 groups： group A （control group）, group B （cobalt protoporphyrin, CoPP）, and group C [CoPP and zinc protoporphyrin （ZnPP）] randomly. A modified rat model of CPB-induced lung injury was established. And then the lung tissues were taken at different times for the relevant indicators test： before CPB （T0）, immediately after CPB （T1）, 2 h after CPB （T2）, 6 h after CPB （T3）, 12 h after CPB （T4）, and 24 h after CPB （T5）. The expression of HO-1 and Bcl-2 protein in each group was tested by immunohistochemistry, and cell apoptosis by TUNEL. Results The HO-1 protein expression in group B was significantly higher than that in groups A and C at any given time point, so was the HO-1 activity （P〈0.05）. There was no significant difference in Bcl-2 expression of lung tissue before CPB among each group （P〉0.05）. The Bcl-2 protein reduced gradually after CPB. The expressions of Bcl-2 protein in group B at all time points after bypass were significantly higher than that in groups A and C （P〈0.05）. The apoptosis index （AI） showed no significant difference before CPB in each group （P〉0.05）, and increased gradually after CPB. AI in group B at any time point after bypass was lower than that in groups A and C （P〈0.05）. The HE staining results showed that the damage of lung tissue in group B obviously reduced compared with groups A and C. Conclusion CoPP can induce a large amount of HO-1 expression in the lung tissue, and it is still highly expressed after CPB. So it plays an important role in anti-apoptosis through the up-regulation of Bcl-2 protein expression.

关 键 词：血红素加氧酶-1 体外循环 肺损伤 细胞凋亡 

分 类 号：R654.1[医药卫生—外科学]