褪黑素对全肝缺血再灌注大鼠肺细胞凋亡的影响及相关机制

Effects of melatonin on pneumocyte apoptosis during total hepatic ischemia-reperfusion in rats and related mechanism

目的探讨褪黑素对全肝缺血再灌注大鼠肺组织细胞凋亡的影响作用及相关机制。方法30只SD大鼠随机分3组:褪黑素治疗组,缺血再灌注组与假手术对照组。阻断肝门30 min后开放血流,建立大鼠全肝缺血再灌注模型。褪黑素组与缺血再灌注组分别于肝门阻断前15 min和再灌注前10 min静脉注射褪黑素溶液或相同剂量溶剂,于再灌注1 h处死动物。假手术组不阻断肝门,于上述各相应时间点注射溶剂与处死动物。留取肺脏组织,原位末端转移酶(TUNEL)法检测细胞凋亡、PCR法检测Bcl-XL与Bax mRNA表达,考马斯亮兰法检测肺泡灌洗液(BALF)总蛋白含量,同时进行肺组织病理学检查。结果与缺血再灌注组相比,褪黑素组病理学改变减轻;BALF总蛋白含量、细胞凋亡指数(AI)与Bax mRNA表达显著降低(P<0.01);而Bcl-XL mRNA表达及Bcl-XL/Bax比值显著增加(P<0.01)。结论褪黑素可能通过影响Bcl-XL/Bax比值来抑制大鼠全肝缺血再灌注后肺细胞凋亡。

Objective To explore the effects of melatonin on pneumocyte apoptosis during total hepatic ischemia-reperfusion（I/ R） in rats and its related mechanism.Methods 30 rats were randomly divided into 3 groups：melatonin group,I/R group and shamoperation group. Total hepatic I/R was produced by occlusion of hepatic helium for 30 minutes, and the occlusion was then released for reperfusion.In melatonin and I/R group, melatonin （0.5%, 10 mg/kg ）or vehicle of the same volume was injected via femoral vein 15 min before isehemia and 10 min before reperfusion, the animals were killed at lh of reperfusion. In sham-operation group,the hepatic helium wasn＇t occluded,the vehicle was injected and the animals were killed at corresponding time. Then the lung tissue was taken for determation of protein content in BALF, apoptotic cells, Bct-XL mRNA, Bax mRNA expression and histological examination. Results Compared with that in I/R group,the histological changes was less severe;the protein content in BALF ,the apoptotic index and the Bax mRNA expression was significantly decreased（ P 〈 0. 01 ）, while the Bcl-XL mRNA expression and Bcl-XL/Bax ratio was significantly increased（ P 〈 0. 01 ）. Conclusion Melatonin can inhibited apoptosis in lung tissues during total hepatic isehemia-reperfusion in rats, which may be mediated by regulation of Bcl-XL/Bax ratio.