熊胆粉对二甲基亚硝胺诱发大鼠肝纤维化的抑制作用

Inhibitory effects of bear bile powder on dimethylnitrosamine-induced liver fibrosis in rats

目的:探讨熊胆粉对二甲基亚硝胺(dimethylnitrosamine,DMN)诱发大鼠肝纤维化的抑制作用.方法:将30只大鼠随机分为正常组、模型组及熊胆组,每组各10只.用10g/LDMN腹腔注射诱发大鼠肝纤维化模型,用400mg/kg熊胆粉灌胃共4wk,检测血清AST、ALT值和总蛋白(TP)含量.肝组织做HE、直接红染色,观察肝组织的病理变化,并检测肝组织内胶原纤维的面密度.免疫组化采用SP法,利用单克隆抗体ED1和α-SMA观察库普弗细胞(Kupffercell,KC)和肝星状细胞(hepaticsatellitecell,HSC)的数量及分布.结果:熊胆组与模型组比较血清ALT值下降,AST值明显下降(4370.87±1338.60nkat/Lvs5741.15±1000.20nkat/L,P<0.05),TP升高,肝/体质量比增加,胶原纤维的面密度明显下降(6.73±1.31vs9.90±1.93,P<0.01).熊胆组肝组织病理变化较模型组轻,纤维间隔变细、或消失,形成弥漫性肝硬化的少.KC和HSC在增生的纤维组织及间隔内分布,熊胆组两种细胞的数量明显减少.结论:熊胆粉具有较好的抑制DMN诱发大鼠肝纤维化的作用,其机制可能与抑制KC,减少细胞因子的分泌,从而抑制HSC的激活和转化,减少胶原纤维合成和分泌有关.

AIM： To investigate the inhibitory effect of bear bile powder on rat liver fibrosis induced by dimethylnitrosamine （DMN）. METHODS： A total of 30 rats were randomly divided into 3 groups： normal control group, model group, and bear bile group （10 in every group）. The rat liver fibrosis model was induced by peritoneal injection of DMN （10 g/L） for 4 wk. At the same time, the rats in the bear bile group received bear bile powder （400 mg/kg） orally once a day for 4 wk. Then the activities of serum alanine transaminase （ALT）, aspartate transaminase （AST）, and the contents of total protein （TP） were detected. Meanwhile, the pathological changes of liver tissues were observed under light microscope after HE staining, and the area density of collagenous fiber were examined. The amount and distribution of Kupffer cell （KC） and hepatic stellate cell （HSC） were detected by immunohistochemical SP method through the distribution of ED1 and α-smooth muscle actin （α-SMA）.RESULTS： Compared with that in the model group, the level of serum ALT was decreased, and AST was significantly decreased （4 370.87±1 338.60 nkat/L vs 5 741.15±1 000.20 nkat/L, P 〈0.05） in the bear bile group. The TP content and the ratio of liver to body weigh were increased. The area density of collagenous fiber was notably decreased （6.73±1.31 vs 9.90±1.93, P 〈0.01）. The pathological changes were lighter, and the occurrence rate of diffused liver fibrosis was lower in the bear bile group than those in the model group. The fibrous septa became thin or disappeared, and the expressions of ED1 and α-SMA were markedly reduced in the bear bile group.CONCLUSION： The bear bile powder can prevent DMN- induced rat liver fibrosis, and the mechanism may relate to its inhibition on the activation of the HSC and KC.