红景天甙对拟高原缺氧大鼠肝损伤的保护作用

Protective effect of salidroside on liver injury of rats under altitude hypoxia simulation

背景:大量流行病学调查表明,高原低氧环境可能导致肝脏损伤,但对其发病机制的研究还相对较少。红景天甙为藏药红景天的主要活性成分,具有清除氧自由基,保护细胞膜等功能。目的:以肝动脉结扎模拟高原肝脏缺氧,了解高原缺氧对大鼠肝损伤的影响,并验证药物红景天甙对拟高原缺氧大鼠肝损伤的保护作用。方法:将Wistar大鼠按随机数字表法分为3组,结扎组制备肝动脉结扎模型;红景天甙+结扎组分别于结扎前2d,1d、结扎前2h腹腔注射红景天甙灭菌水溶液,两组分别分为结扎1,2,4,6,8h五个时间段;设正常对照组。以全自动生化分析仪检测血清肝功能变化,硫代巴比妥酸法检测丙二醛含量,黄嘌呤氧化酶法检测超氧化物歧化酶活性,苏木精-伊红染色观察肝组织病理学变化,免疫组化检测肝组织缺氧诱导因子1α蛋白水平变化,TUNEL法观察肝组织凋亡情况。结果与结论:通过大鼠肝动脉结扎模拟高原肝脏缺氧可引起肝脏急性损伤。红景天甙干预处理可使大鼠血清肝功指标得到改善(P<0.05);降低肝组织丙二醛含量、升高超氧化物歧化酶活性(P<0.05);减轻肝组织病理学变化;上调缺氧诱导因子1α蛋白表达水平(P<0.05)、减少细胞凋亡(P<0.05)。提示药物红景天甙可通过抗氧化应激损伤,抑制细胞凋亡起到对拟高原缺氧大鼠急性肝损伤的保护作用。

BACKGROUND： Epidemiologic survey demonstrated that high-altitude hypoxia may result in liver injury, but there are few studies relate to the pathogenesis. Salidroside, the main active component of Gold Theragran, has been showed effects on removing oxygen free radical and protecting cell membrane. OBJECTIVE： To observe the protective effect of salidroside on rat’s liver injury caused by imitating altitude liver hypoxia with hepatic artery ligation. METHODS： Wistar rats were randomly divided into 3 groups： ligation group, salidroside ＋ ligation group and normal control group. Rats in the former two groups were prepared for hepatic artery ligation models and divided into five time sections as 1, 2, 4, 6, 8 hours. In the salidroside ＋ ligation group, rats were intraperitoneal injected salidroside solution at 2 days, 1 day and 2 hours prior to ligation. Liver function targets in serum were detected by automatic biochemistry analyzer; the content of malonaldehyde was detected by thiobarbituric acid method; the activity of superoxide dismutase （SOD） was detected with xanthine oxidase method; pathological changes in liver tissue were observed by hematoxylin-eosin staining; the level of hypoxia-inducible factor 1α （HIF-1α） protein was detected with immunohistochemistry; and apoptosis in liver tissue was detected by TUNEL method. RESULTS AND CONCLUSION： Imitating altitude liver hypoxia by hepatic artery ligation could cause liver’s acute injury. Intervention with salidroside could improve rat’s liver function targets （P 0.05）, lower the content of malonaldehyde and heighten the activity of SOD （P 0.05）, abate liver tissue’s histopathological change, increase HIF-1α protein level （P 0.05）, and lessen cell apoptosis in liver tissues （P 0.05）. Salidroside have protective effect on rat’s acute liver injury induced by imitating altitude liver hypoxia with hepatic artery ligation by opposing oxidative stress and inhibiting cell apoptosis.