目的 觀察仁青芒覺膠囊對(duì)二甲基亞硝胺（DMN）誘導(dǎo)的肝纖維化模型大鼠的治療作用。方法 大鼠ip DMN制備肝纖維化模型，治療給予低、中、高劑量（0.05、0.10、0.20 g/kg）的仁青芒覺膠囊，1.5 g/kg扶正化瘀膠囊作為陽性藥，對(duì)照組及模型組給予同體積的蒸餾水，每天給藥1次，連續(xù)4周。觀察大鼠血清生化及膠原水平，肝臟組織蛋白、羥脯氨酸（Hyp）及超氧化物歧化酶（SOD）水平的變化；取肝臟，測(cè)定肝臟指數(shù)；肝組織固定，HE及Masson染色，鏡下觀察肝臟組織結(jié)構(gòu)和纖維化程度變化。結(jié)果 ①與模型組比較，仁青芒覺膠囊各劑量組動(dòng)物體質(zhì)量，高、低劑量組肝質(zhì)量顯著增加（P<0.05、0.01），高劑量組動(dòng)物肝臟系數(shù)明顯增加（P<0.05）。②與模型組比較，仁青芒覺膠囊各劑量組血清總蛋白（TP）和白蛋白（ALB）含量顯著升高，血清丙氨酸轉(zhuǎn)氨酶（ALT）、天冬氨酸轉(zhuǎn)氨酶（AST）活性和總膽紅素（TBIL）、透明質(zhì)酸（HA）、IV型膠原（IV-C）、Ⅲ型前膠原（PC-Ⅲ）含量顯著降低（P<0.05、0.01、0.001）；層粘蛋白（LN）也有不同程度的降低，低劑量組差異顯著（P<0.05）。③與模型組比較，低、中劑量的仁青芒覺膠囊可以顯著增加肝組織中蛋白含量（P<0.01、0.001），各劑量SOD水平均顯著升高（P<0.05、0.001）。④肝組織病理學(xué)顯示，0.2 g/kg劑量的仁青芒覺膠囊能夠顯著改善彌漫性肝細(xì)胞水腫變性、壞死及減輕纖維增生程度，中、低劑量可以改善肝纖維化程度。結(jié)論 仁青芒覺膠囊對(duì)DMN誘導(dǎo)的肝纖維化模型大鼠具有一定程度的治療作用。

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

國(guó)家科技重大新藥創(chuàng)制項(xiàng)目（2015ZX09501004）；天津市科技計(jì)劃項(xiàng)目（16PTG CCX00090）#