雷帕霉素对梗阻性黄疸大鼠肝脏的保护作用

Hepatoprotective effect of rapamycin in rats with obstructive jaundice

目的:探讨雷帕霉素(rapamycin)对梗阻性黄疸(OJ)大鼠肝脏的保护作用。方法:将54只SD大鼠随机均分为假手术组,OJ模型组(模型组),OJ模型+雷帕霉素治疗组(治疗组)。采用胆总管结扎方法建立梗阻性黄疸模型,治疗组大鼠术后给予雷帕霉素0.4 mg/(kg.d)皮下注射,假手术组与模型组同期皮下注射等量生理盐水,分别于术后1,3,5 d每组取6只大鼠,行白细胞(WBC)计数、血浆内毒素(ET)含量与肝功能指标检测;RT-PCR测肝组织肿瘤坏死因子α(TNF-α)mRNA的表达;观察肝组织病理学变化。结果:除假手术组外,模型组与治疗组大鼠术后均出现OJ表现,但治疗组症状轻于模型组;模型组与治疗组大鼠WBC计数,血浆谷丙转氨酶(ALT),总胆红素(TBIL),ET水平,肝组织TNF-αmRNA水平在术后各时间点均较假手术组明显升高(均P<0.05);病理学观察显示,模型组与治疗组大鼠肝组织均表现为肝血窦扩张,肝细胞坏死,胆管细胞增生及炎性细胞浸润等病理改变;模型组与治疗组间比较,治疗组以上指标在各时间点上均低于模型组(均P<0.05),病理改变也明显轻于模型组。结论:雷帕霉素对梗阻性黄疸大鼠的肝脏具有保护作用,机制部分可能与其抑制全身炎症反应有关。

Objective： To investigate the hepatoprotective effect ofrapamycin in rats with obstructive jaundice （OJ）. Methods： Fifty-four SD rats were equally randomized into sham operation group, OJ model group （model group） and OJ model plus rapamycin treatment group （treatment group）. The rat OJ model was established by common bile duct ligation. Rats in treatment group received rapamycin 0.4 mg/kg once daily by subcutaneous injection after operation, and rats in both sham operation group and model group were given normal salineof the same volume instead. Six rats in each group were sacrificed at the postoperative day （POD） 1, 3 and 5 respectively, and the white blood cell （WBC） count, plasma endotoxin （ET） level and liver function parameters were determined, the mRNA expression levels of tumor necrosis factor a （TNF-α） in the liver tissues were measured by RT-PCR and liver pathological changes were also observed. Results： Except for the rats in sham operation group, rats in both model group and treatment group presented overt OJ manifestations, but those of rats in treatment group were milder than those in model group; the WBC count, plasma levels of alanine aminotransferase （ALT）, total bilirubin （TBIL） and ET as well as the TNF-a mRNA level in the liver tissue were significantly higher in both model group and treatment group than those in sham operation group at each observation time point （all P〈0.05）, As shown by pathological studies in the liver specimens from rats in both model group and treatment group, there were pathological changes that included the dilatation of liver sinusoids, hepatocyte necrosis, hyperplastic bile duct cells and inflammatory cell infiltration. The comparison between model group and treatment group showed that all the determined variables were significantly lower in treatment group than those in model group at each observation time point （all P〈0.05）, and liver pathological damages were also milder in treatment group than those in model group. Conclusion： Rapamycin has hepatoprotective effect in OJ rats, and the mechanism may be partially due to its inhibition of the systemic inflammatory response.