目的 观察仁青芒觉胶囊对二甲基亚硝胺（DMN）诱导的肝纤维化模型大鼠的治疗作用。方法 大鼠ip DMN制备肝纤维化模型，治疗给予低、中、高剂量（0.05、0.10、0.20 g/kg）的仁青芒觉胶囊，1.5 g/kg扶正化瘀胶囊作为阳性药，对照组及模型组给予同体积的蒸馏水，每天给药1次，连续4周。观察大鼠血清生化及胶原水平，肝脏组织蛋白、羟脯氨酸（Hyp）及超氧化物歧化酶（SOD）水平的变化；取肝脏，测定肝脏指数；肝组织固定，HE及Masson染色，镜下观察肝脏组织结构和纤维化程度变化。结果 ①与模型组比较，仁青芒觉胶囊各剂量组动物体质量，高、低剂量组肝质量显著增加（P<0.05、0.01），高剂量组动物肝脏系数明显增加（P<0.05）。②与模型组比较，仁青芒觉胶囊各剂量组血清总蛋白（TP）和白蛋白（ALB）含量显著升高，血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）活性和总胆红素（TBIL）、透明质酸（HA）、IV型胶原（IV-C）、Ⅲ型前胶原（PC-Ⅲ）含量显著降低（P<0.05、0.01、0.001）；层粘蛋白（LN）也有不同程度的降低，低剂量组差异显著（P<0.05）。③与模型组比较，低、中剂量的仁青芒觉胶囊可以显著增加肝组织中蛋白含量（P<0.01、0.001），各剂量SOD水平均显著升高（P<0.05、0.001）。④肝组织病理学显示，0.2 g/kg剂量的仁青芒觉胶囊能够显著改善弥漫性肝细胞水肿变性、坏死及减轻纤维增生程度，中、低剂量可以改善肝纤维化程度。结论 仁青芒觉胶囊对DMN诱导的肝纤维化模型大鼠具有一定程度的治疗作用。

Objective To investigate the therapeutic effect of Renqing Mangjue capsule (RQMJC) on liver fibrosis in rats induced by dimethylnitrosamine (DMN). Methods Liver fibrosis rats induced by DMN were administered with RQMJC via gastro-gavage at the levels of 0.05, 0.10 and 0.20 g/kg once daily for 4 weeks. Fuzheng Huayu Capsule of 1.5 g/kg was used as positive drug. Rats in control and model group were given distilled water of the same volume. Serum chemistry, serum collagens, as well as liver SOD, protein and hydroxyproline (Hyp) were examined at the end of study. Liver was taken and liver index was measured. Histopathology with HE and Masson's trichrome staining was used to evaluate the changes of hepatocyte morphology and fibrosis degree. Results ①Compared with model group, the body weight in all dosing groups, the liver weight in high and low dose groups were increased significantly (P<0.05 and 0.01), and the animal liver coefficient increased significantly in the high dose group (P<0.05). ② Compared with model group, the content of total serum protein (TP) and albumin (ALB) of each dose group of RQMJC was significantly increased, the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), hyaluronic acid (HA), type IV collagen (IV-C) and type Ⅲ procollagen (PC-Ⅲ) were significantly decreased (P<0.05, 0.01, 0.001). Laminin (LN) had the trend of reduction, and the difference was significant in low dose group (P<0.05). ③Compared with model group, low and medium doses of RQMJC significantly increased the protein content in liver tissue (P<0.01, 0.001), and the SOD levels of each dose group were significantly increased (P<0.05, 0.001). ④Liver histopathology showed that 0.2 g/kg RQMJC significantly improved the degree of edema, degeneration, necrosis and fibrosis of diffuse hepatocytes, and medium and low dose groups of RQMJC improved the degree of liver fibrosis. Conclusions RQMJC is effective in the treatment of liver fibrosis induced by DMN in rats.

R962.2

国家科技重大新药创制项目（2015ZX09501004）；天津市科技计划项目（16PTG CCX00090）#