八宝丹对二甲基亚硝胺诱导的大鼠肝纤维化干预作用研究

Intervention of Babaodan capsule on liver fibrosis induced by dimethylnitrosamine in rats

目的观察八宝丹对二甲基亚硝胺(DMN)诱导的大鼠肝纤维化的干预作用。方法 90只SD雄性大鼠随机分为对照组和造模组,以0.5%DMN按2μl/g体质量腹腔注射4周复制大鼠肝纤维化模型。4周末造模组大鼠随机分为模型组,八宝丹高、中、低剂量组,扶正化瘀组;用药各组灌胃相应药物,正常组和模型组灌胃等剂量的0.5%羧甲基纤维素钠(CMC),给药4周。8周末处死动物,留取标本。检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)活性和白蛋白(ALB)、总胆红素(TBIL)含量;测定肝组织中羟脯氨酸(Hyp)含量;HE染色和天狼猩红染色观察肝组织病理学改变。结果与正常组比较,模型组血清TBIL、ALT、AST水平明显升高(P<0.05),各药物组干预后,血清学指标TBIL、ALT、AST均有所降低;HE染色显示模型组肝脏内有大量炎性细胞浸润、肿胀、变性坏死,有明显出血现象;天狼猩红染色显示模型组大鼠肝脏胶原增生明显,形成假小叶,胶原面积明显增加;模型组肝组织Hyp含量较正常组明显升高(P<0.01),药物干预后肝组织炎症和纤维化程度较模型组均有所改善,肝组织羟脯氨酸含量明显降低,高、中剂量八宝丹组和扶正化瘀组较模型组肝组织胶原沉积明显减轻(P<0.05),扶正化瘀组与八宝丹高剂量组比较差异无统计学意义(P>0.05)。结论八宝丹对DMN诱导的大鼠肝纤维化有较好的逆转作用,高剂量八宝丹的疗效相对于中低剂量的八宝丹更为突出;八宝丹高剂量组与阳性对照药物扶正化瘀胶囊组对大鼠肝纤维化的干预效果类似。

Objective To observe the intervention of Babaodan capsule on liver fibrosis induced by dimethylnitrosamine（ DMN） in rats. Methods 90 SpragueDawley male rats were randomly divided into the normal group and modeling group. The rat model of hepatic fibrosis was established by intraperitoneal injection of0. 5 % DMN at the dose of 2 μl / g for 4 weeks. At the end of the fourth week,the rats in the modeling group were randomly divided into the model group,Babaodan capsule groups with high-,medium- and low-dose,Fuzheng Huayu group. Treatment drugs were orally given to the corresponding groups. The normal group and model group were treated with equivalent dose of 0. 5% sodium carboxymethyl cellulose（ CMC）. The treatment course was 4 weeks. At the end of the 8th week,animals were sacrificed and the samples were collected. The serum levels of alanine aminotransferase（ ALT）,aspartate aminotransferase（ AST）,albumin（ ALB）,total bilirubin（ TBIL） and the hepatic levels of hydroxyproline（ Hyp） were detected. Pathological changes of liver tissue was observed by sirius red staining and HE staining. Results Compared with the normal group,the serum levels of ALT,AST and TBIL in the model group were significantly increased（ P〈0. 05）,after drug intervention the serum levels of ALT,AST and TBIL were all decreased. HE staining showed that there were a large amount of inflammatory cell infiltration,swelling,degeneration and necrosis,significant bleeding phenomenon in the liver tissue of rats in the model group. Sirius red staining showed that there was obvious hyperplasia of liver collagen with false lobules in the model group. Compared with the normal group,the collagen area and hepatic Hyp content in the model group were significantly increased（ P〈0. 01）. After drug intervention,the degree of inflammation and fibrosis in liver tissue were all improved compared with the model group,and the hepatic Hyp content was decreased significantly. The collagen deposition in liver tissue in the Babaodan capsule groups with high-and medium-dose and Fuzheng Huayu group were significantly reduced compared with the model group（ P〈0. 05）,and there was no statistically significant difference between the Babaodan capsule group with high-dose and Fuzheng Huayu group. Conclusion Babaodan capsule show better reversal effects on rat liver fibrosis induced by DMN. The intervention effects of Babaodan capsule with high-dose on hepatic fibrosis in rats are more prominent compared with the medium-and low-dose,which is similar to the effects of Fuzheng Huayu Capsule as positive control.