紫衫醇对大鼠肝纤维化的抑制作用及机制研究

发布时间：2018-02-25 22:34

本文关键词： 肝硬化紫杉酚肝星状细胞大鼠　出处：《中国普通外科杂志》2017年09期 　论文类型：期刊论文

【摘要】：目的:探讨紫衫醇对大鼠肝纤维化的抑制作用及其分子机制。方法:将30只Wistar大鼠随机均分为正常对照组、肝纤维化模型组,肝纤维化模型+紫衫醇组,肝纤维化模型用腹腔注射二甲基亚硝胺每日1次连续7 d诱导,之后,肝纤维化模型+紫衫醇组大鼠给予尾静脉注射紫杉醇液,隔日1次,共3次;实验结束时,处死大鼠观察肝脏病理学和血清学指标变化,及肝组织中肝星状细胞标志物α-SMA的表达。将大鼠肝星状细胞HSC-T6分别用TGF-β1、紫杉醇+TGF-β1处理,以无处理的HSC-T6细胞为对照,分别检测各组细胞纤连蛋白及I、III型胶原m RNA与蛋白的表达。结果:正常对照组肝组织无病理学改变,肝纤维化模型组出现肝纤维化病变,肝纤维化模型+紫杉醇组可见肝组织中度坏死,无明显坏死结节;与正常对照组比较,肝纤维化模型组与肝纤维化模型+紫杉醇组转氨酶、总胆红素(TIBL)、透明质酸(HA)水平均明显升高,白蛋白(ALB)水平明显降低(均P0.05),后者较前者在TBIL、ALB、HA方面有明显改善(均P0.05);正常对照组肝组织无明显α-SMA表达,肝纤维化模型组和与肝纤维化模型+紫杉醇组肝组织均有α-SMA表达,后者的α-SMA阳性细胞数明显少于前者(P0.05);与无处理的HSC-T6细胞比较,TGF-β1与紫杉醇+TGF-β1处理后的HSC-T6细胞纤连蛋白及I、III型胶原m RNA与蛋白均明显上调(均P0.05),后者的上调程度明显低于前者(均P0.05)。结论:紫杉醇可抑制大鼠肝纤维化的产生和发展,机制可能与其抑制肝星状细胞中TGF-β信号通路从而减少肝星状细胞活化有关。
[Abstract]:Objective: to investigate the inhibitory effect of Violatol on hepatic fibrosis in rats and its molecular mechanism. Methods: 30 Wistar rats were randomly divided into three groups: normal control group, hepatic fibrosis model group, and hepatic fibrosis model group. The hepatic fibrosis model was induced by intraperitoneal injection of Dimethylnitrosamine once a day for 7 days, and then rats in the hepatic fibrosis model group were given paclitaxel solution once every other day for 3 times, and at the end of the experiment, the rats in the hepatic fibrosis model group were given paclitaxel solution once every other day. The hepatic stellate cells (HSC-T6) were treated with TGF- 尾 1 and paclitaxel TGF- 尾 1, respectively, and the untreated HSC-T6 cells were used as control, the hepatic stellate cells were treated with TGF- 尾 1 and paclitaxel TGF- 尾 1, respectively, and the expression of hepatic stellate cell marker 伪 -SMA was observed. Results: there were no pathological changes in normal control group and hepatic fibrosis model group. Hepatic fibrosis model group showed moderate necrosis of liver tissue without obvious necrotic nodules, and hepatic fibrosis model group and paclitaxel group showed transaminase, compared with normal control group. The levels of total bilirubin, hyaluronic acid and hyaluronic acid (HA) were significantly increased, and the level of Alb was significantly decreased (all P 0.05), the latter was significantly improved compared with the former (all P 0.05), and there was no obvious 伪 -SMA expression in normal control group. 伪 -SMA expression was observed in hepatic fibrosis model group and paclitaxel group. The number of 伪 -SMA positive cells in the latter was significantly lower than that in the former (P 0.05), and the fibronectin and type III collagen m RNA and protein in the HSC-T6 cells treated with TGF- 尾 1 and taxol TGF- 尾 1 were significantly higher than those in the untreated HSC-T6 cells (P 0.05, respectively). Conclusion: paclitaxel can inhibit the production and development of hepatic fibrosis in rats. The mechanism may be related to the inhibition of TGF- 尾 signaling pathway in hepatic stellate cells, thereby reducing the activation of hepatic stellate cells.
【作者单位】：中南大学湘雅医院普通外科;
【基金】：湖南省科技重点研发计划基金资助项目(2015SK20482)
【分类号】：R575.2

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