淫羊藿素脂质体抗大鼠肝脏缺血再灌注损伤

目的 探讨淫羊藿素脂质体对大鼠肝脏缺血再灌注(I/R)损伤的作用及其机制.方法 建立大鼠70％肝脏I/R损伤模型.将120只雄性大鼠随机分成淫羊藿素脂质体+I/R损伤(ICT+ I/R)组、空白脂质体+I/R损伤(LIP+I/R)组、单纯I/R损伤组和假手术(Sham)组,每组再随机分成2h和6h两个亚组.Sham组仅游离肝门,其余各组均行70％肝脏缺血60 min.血流阻断前10 min,ICT+I/R组、LIP+I/R组分别经门静脉注射淫羊藿素脂质体(1.5 mg/kg)、空白脂质体(与淫羊藿素脂质体等体积),I/R组和Sham组不行任何预处理.经2、6h血流再灌注后,采集各组血液及肝脏组织标本,检测血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平以及肝组织中超氧化物歧化酶(SOD)、丙二醛(MDA)、一氧化氮(NO)、一氧化氮合酶(NOS)、诱导型一氧化氮合酶(iNOS)、内皮型一氧化氮合酶(eNOS)以及髓过氧化物酶(MPO)含量.采用H-E染色法观察肝脏组织形态,TUNEL染色法观察肝细胞凋亡情况并测定凋亡指数(AI).结果 再灌注2h,IGT+I/R组的ALT、MDA、MPO、AI较LIP+I/R组和I/R组下降,差异有统计学意义(P＜0.O1);再灌注6h,与LIP+ I/R组和I/R组相比,ICT+ I/R组的ALT、AST、MDA、AI下降,同时SOD、NO、NOS、eNOS升高,差异有统计学意义(P＜0.05,P＜0.01).结论 淫羊藿素脂质体能够通过增加SOD含量、减少MDA的生成,促进eNOS表达的升高、增加NO的含量以及抑制MPO的聚集、减少肝细胞凋亡等多途径发挥抗大鼠肝脏I/R损伤的保护作用.

Protective effect of icaritin lipsome against hepatic ischemia/reperfusion injury in rats and its mechanism

Objective The present study aimed to investigate the effects of icaritin liposme on following hepatic ischemia /reperfusion(I/R) injury in rats. Methods A total of 120 male Sprague-Dawley rats were randomly divided into four groups: icaritin liposome(ICT+I/R) group, vechicle liposome(LIP+I/R) group, ischemia/reperfusion(I/R) group and sham operated(SHAM) group. Each group was randomly divided into two subgroups of 2 h and 6 h. Except for SHAM group, all rats were subjected to 70% liver ischemia for 60 min. Icaritin liposome or vechile lipsome was injected through the portal vein at 1.5 mg/kg(the same volume vechile lipsome in LIP+I/R group) 10 min before ischemia. Blood and liver tissues were obtained in all animals at 2h and 6h after reperfusion to assess the following determinations: (1)serumALT/AST; (2)liver tissue superoxide dismutase(SOD), malondialdehyd(MDA), nitric oxide(NO), nitric oxide synthase(NOS), inducible nitric oxide synthase(iNOS), endothelial nitric oxide synthase(eNOS) and myeloperoxidase(MPO); (3) morphological and histological Observation of liver tissues by H-E staining; (4)liver cell apoptoses were evaluated by TUNEL staining. Results Compared with group LIP+I/R and IR, ALT/MDA/MPO/AI decreased significantly in group ICT+I/R at 2h of reperfusion. ALT/AST/MDA/AI in group ICT+I/R were reduced promptly, moreover a higher increase of SOD/NO/NOS/eNOS campared with LIP+I/R and IR group at 6h of reperfusion. Conclusion Icaritin liposome could excert protective efficacy of reducing liver I/R injury via multiway.