目的 观察丹参滴丸对二甲基亚硝胺诱导的大鼠肝纤维化的治疗作用。方法 除对照组外，其余大鼠采用ip二甲基亚硝胺4周诱导大鼠肝纤维化，造模结束后，ig丹参滴丸175、350、700 mg/kg，设扶正化瘀胶囊为阳性对照组（1 500 mg/kg），对照组、模型组给予同体积蒸馏水，1次/d，连续给药4周。末次给药后1 h剖杀动物，测定血清生化（ALT、AST活性及TP、ALB、TBIL含量）、血清胶原（HA、LN、Ⅲ型前胶原、IV型胶原）水平、肝组织中蛋白、Hyp的含量。取肝组织固定，进行HE、Masson染色，镜下观察肝细胞组织结构和肝纤维化程度。结果 丹参滴丸能够显著增加血清中TP和ALB水平，降低ALT、AST活性和TBIL水平；能显著降低LN、Ⅳ型胶原含量，明显降低HA含量，对Ⅲ型前胶原含量有一定的降低趋势；肝匀浆检测显示能显著增加肝组织中蛋白含量，对Hyp含量有一定的降低趋势；肝组织病理学HE染色和Masson染色显示，丹参滴丸能够改善弥漫性肝细胞变性、坏死及炎症反应，能显著抑制胶原增生、减轻肝纤维化程度。结论 丹参滴丸能显著改善大鼠的肝功能、减少肝组织纤维的增生、对二甲基亚硝胺诱导的大鼠肝纤维化有一定的治疗作用。

Objective To study the therapeutic effect of Danshen Dropping Pills on hepatic fibrosis in rats induced by dimethylnitrosamine (DMN). Methods Except the control group, all groups were ip injected with DMN for 4 weeks to induce rat liver fibrosis.After rat model established, the rats in Danshen Dropping Pills group were ig administrated with Danshen Dropping Pills 700, 350, and 175 mg/kg, the rats in positive group with Fuzheng Huayu Capsule (1 500 mg/kg), once daily for 4 weeks, and the rats in control group and model group with distilled water. The activities of alanine transaminase (ALT), aspartate transferase (AST), and the contents of total protein (TP), albumin (ALB), and total bilirubin in serum (TBIL) of rats were examined. Meanwhile, hyaluronic acid (HA), procollagen Ⅲ, collagen type IV, laminin (LN) level in serum, and the contents of protein and hydroxyproline (Hyp) were determined. Then, the liver tissue structure and the degree of liver fibrosis and morphological changes of liver pathology were observed by HE and Masson staining, respectively. Results Danshen Dropping Pills could significantly increase the contents of TP and ALB, markedly inhibit the increasing of ALT, AST and TBIL in serum of rats with hepatic fibrosis, obviusly decrease the contents of LN, collagen type IV and HA, and gradually lower the content of procollagen Ⅲ. There were increase of the content of protein in homogenized liver and could gradually lower Hyp content in liver homogenate test. Danshen Dropping Pills also could improve diffuse liver cell degeneration, necrosis, inflammations in the liver histopathology, significantly inhibit collagen hyperplasia, and reduce the degree of liver fibrosis by HE staining and Masson staining.Conclusion Danshen Dropping Pills can significantly improve the liver function of rats, reduce the proliferation of liver tissue fibers, and have therapeutic effects on DMN-induced rat liver fibrosis.

国家科技重大新药创制项目（2015ZX09501004）