黄芪对梗阻性黄疸幼鼠肝损伤和TGF-β1表达的影响

Effects of Astragalus on Liver Injury and TGF-β1 mRNA Expression in Growing Rats with Obstructive Jaundice

目的 建立幼鼠梗阻性黄疸模型，对模型鼠应用黄芪干预，观察胆道梗阻后肝功能、肝细胞组织学和TGF-β1mRNA表达的改变，探讨黄芪对上述指标的影响。方法 将40只Wistar幼鼠随机分为正常对照组、假手术组、OJ组和OJ＋A组，各10只。OJ组鼠于近肝门处游离并结扎胆总管，假手术组仅做游离不结扎胆总管。OJ＋A组术后1d开始腹腔注射黄芪注射液（250mg/100g体重）共7d，其余组相同时间腹腔注射生理盐水0．5ml。检测实验鼠血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、总胆汁酸（TCA）及肝组织病理形态学，应用RT-PCR技术检测肝组织TGF-β1mRNA表达，对所得数据进行统计学处理。结果 ①OJ组、OJ＋A组AST、ALT、TCA均显著高于正常对照组和假手术组，P〈0．01。②对照组和假手术组肝小叶结构正常，肝细胞索排列规则有序，未见变性、坏死，肝窦与汇管区成纤维细胞少见；OJ组肝细胞淤胆变性，糖原蓄积，脂肪变性。肝细胞胞浆疏松化，气球样变。易见枯否细胞，汇管区纤维组织增生，可见纤维母细胞。OJ＋A组肝细胞胞浆红染，嗜酸性变，肝细胞变性减轻。③OJ组肝组织TGF-β1mRNA基因表达显著高于对照组和OJ＋A组，均P〈0．05。结论 梗阻性黄疸幼鼠模型肝脏结构和功能指标显著改变。幼鼠胆管结扎8d，TGF-β1mRNA表达增强。应用黄芪对梗阻性黄疸诱发的肝脏损害有保护作用。

Objective To evaluate the effects of astragalus on liver injury and TGF-β1 mRNA expression in immature rats with obstrctive jaundice （OJ）. Methods Forty immature male Wistar rats were randomly divided into a control, a sham operation, an OJ, and an OJ＋A groups. Wistar rats in the OJ and OJ＋A group were subjected to common bile duct ligation （CBDL）, while the sham group had the bile duct mobilized but not tied. The control, sham, and OJ groups were given 0.5ml of normal saline by intraperitoneal injection daily. In the OJ＋A group, 250mg/100g body weight of astragalus injection was applied intraperitoneally daily from day 1 to 7 of the study. All animals were sacrificed on postoperative day 8. Liver tissue and peripheral blood were collected. Serum Alanine aminotransferase （ALT）, Aspartate aminotransferase （AST）, and total chofic acid （TCA） level were detected. Hepatic morphological fmdings were observed by fight microscopy. TGF-β1 mRNA were extracted from liver and measured by reverse transcription polymerase chain reaction （RT-PCR）. Data were analyzed using chi-square test and student＇s test （x^- ± s ）, P〈0.05 was considered statistical significance. Results ①Serum AST, ALT, and TCA value in each OJ group were significantly higher than that of the control and sham operation groups. ②In the control and sham operation group, normal structure of the fiver remained, but in the OJ group, obvious degeneration of hepatocytes was detected, such as cholastasis, starch accumulation, and fatty degeneration. Kupffer cells and dilated Disse＇space were common in the OJ group. In the OJ group, histopathologic findings of the liver demonstrated intense degree of fibrosis, but in the OJ＋A group, typical changes of large duct obstruction were significantly improved after astragalus injection treatment. ③The TGF-β1 mRNA over-expression in the OJ group was seen compared with the control and the OJ＋ A groups. Conclusion ①In growing rat model of experimental obstructive jaundice, hepatic morphology and fiver biochemical tests altered significantly. ②The administration of astragalus can ameliorate liver damage and diminish expression of TGF-β1 mRNA of hepatic tissue, thus administration of astragalus may be effective in preventing hepatic injury in growing rats with obstructive jaundice.