目的 觀察丹參滴丸對(duì)二甲基亞硝胺誘導(dǎo)的大鼠肝纖維化的治療作用。方法 除對(duì)照組外，其余大鼠采用ip二甲基亞硝胺4周誘導(dǎo)大鼠肝纖維化，造模結(jié)束后，ig丹參滴丸175、350、700 mg/kg，設(shè)扶正化瘀膠囊為陽(yáng)性對(duì)照組（1 500 mg/kg），對(duì)照組、模型組給予同體積蒸餾水，1次/d，連續(xù)給藥4周。末次給藥后1 h剖殺動(dòng)物，測(cè)定血清生化（ALT、AST活性及TP、ALB、TBIL含量）、血清膠原（HA、LN、Ⅲ型前膠原、IV型膠原）水平、肝組織中蛋白、Hyp的含量。取肝組織固定，進(jìn)行HE、Masson染色，鏡下觀察肝細(xì)胞組織結(jié)構(gòu)和肝纖維化程度。結(jié)果 丹參滴丸能夠顯著增加血清中TP和ALB水平，降低ALT、AST活性和TBIL水平；能顯著降低LN、Ⅳ型膠原含量，明顯降低HA含量，對(duì)Ⅲ型前膠原含量有一定的降低趨勢(shì)；肝勻漿檢測(cè)顯示能顯著增加肝組織中蛋白含量，對(duì)Hyp含量有一定的降低趨勢(shì)；肝組織病理學(xué)HE染色和Masson染色顯示，丹參滴丸能夠改善彌漫性肝細(xì)胞變性、壞死及炎癥反應(yīng)，能顯著抑制膠原增生、減輕肝纖維化程度。結(jié)論 丹參滴丸能顯著改善大鼠的肝功能、減少肝組織纖維的增生、對(duì)二甲基亞硝胺誘導(dǎo)的大鼠肝纖維化有一定的治療作用。

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.

國(guó)家科技重大新藥創(chuàng)制項(xiàng)目（2015ZX09501004）