大鼠肝缺血/再灌注后肝组织一氧化氮和不同亚型一氧化氮合酶的变化

Changes of nitric oxide and nitric oxide synthase during hepatic ischemia/reperfusion of rat

目的探讨一氧化氮(NO)和一氧化氮合成酶(NOS)在肝缺血/再灌注(I/R)过程中的变化和作用。方法健康雄性SD大鼠24只,随机分为3组(每组8只):①正常对照组,术中只分离肝周围韧带,不做肝门阻断及再灌注。②I/R组,进行45 min的部分肝门阻断及60 min的再灌注。③L-精氨酸(L-Arg)组,缺血前20 min经阴茎背静脉注射L-Arg(300 mg/kg),余同②组。实验结束后,取下腔静脉血2 ml,并迅速切取缺血肝组织。检测血清丙氨酸转氨酶(ALT)、门冬氨酸转氨酶(AST)、乳酸脱氢酶(LDH);测定肝组织中超氧化物歧化酶(SOD)、丙二醛(MDA)、黄嘌呤氧化酶(XOD)、一氧化氮(NO)和一氧化氮合成酶(NOS)等指标;观察光镜和电镜下肝组织学变化。结果与正常对照组相比,I/R组iNOS升高,NO降低;L-Arg组NOe、NOS均高于I/R组。2、3组比1组大鼠的肝组织病理损害重、肝功能差,L-Arg组病理损害较I/R组明显减轻、肝功能改善。结论NO对大鼠肝I/R损伤具有保护作用,不同亚型NOS的变化参与其中。

Objective To explore changes and effects of nitric oxide （NO） as well as nitric oxide synthase （NOS） during liver ischemia/reperfusion （I/R） injury of rats. Methods Twenty-four healthy male SD rats were randomly divided into 3 groups （8 animals per group）. Group 1 was served as sham operated control. Both Group 2 and Group 3 were subjected to 45 min lobar, rather than total hepatic ischemia and 60 min reperfusion. Group 3 were pretreated with L-Arg （300 mg/kg） via the dorsal penis vein additionally. Blood samples （2 ml） were drawn from inferior vena cava for biochemistry tests, such as ALT, AST, and LDH. Injured liver lobes were excised for histology and testing SOD, MDA, XOD, NO and NOS. Results Rats in group 2 showed significantly higher iNOS levels and lower NO levels than those in group 1. NO and eNOS were increased in Group 3 compared with those in group 2 （P〈0.05）. The L-Arg administration significantly reduced the hepatic lesions. Conclusion NO has a protective effect on liver I/R injury in rats, and different isoforms of NOS may be involved in this process.