丹参多酚酸盐对肝硬化门静脉高压抑制作用的研究

Study on inhibitory effect of Salvianolate on portal hypertension in liver cirrhosis

关键词:  丹参多酚酸盐  肝硬化  门静脉高压  二甲基亚硝胺  秋水仙碱

Key words:  Salvianolate  liver fibrosis  portal hypertension  DMN  colchicine

摘要:

[目的] 研究丹参多酚酸盐对大鼠肝硬化门静脉高压的抑制作用。[方法] 采用腹腔注射二甲基亚硝胺（DMN），每周前3天注射，共4周的方法制备肝硬化门静脉高压大鼠模型，设正常对照组、模型组（生理盐水）、丹参多酚酸盐[12、24、48 mg/（kg·d）]治疗组和秋水仙碱[0.1 mg/（kg·d）]治疗组，每组20只，疗程6周。测定血清中转氨酶、总胆红素（TBIL）、肝纤四项[（IV型胶原（C-IV）、Ⅲ型前胶原（PC-Ⅲ）、透明质酸酶（HA）、层粘连蛋白（LN）]含量和肝脏中羟脯氨酸（HYP）水平，通过苏木精-伊红（HE）染色观察肝脏组织病变，记录门静脉压（PVP）、门静脉血流量（PVF）、平均动脉压（MAP）和心率（HR）；测定肝脏中丙二醛（MDA）含量和抗氧化酶活性。[结果] 经丹参多酚酸盐[24、48 mg/（kg·d）]组治疗能够显著降低肝硬化门静脉高压大鼠血清中谷丙转氨酶（ALT）、谷草转氨酶（AST）、TBIL、IV型胶原（C-IV）、Ⅲ型前胶原（PC-Ⅲ）、透明质酸酶（HA）、HYP含量（P<0.05或P<0.01）；降低PVP和PVF（P<0.05）；提高肝脏中超氧化物歧化酶（SOD）、过氧化氢酶（CAT）活性并降低MDA含量（P<0.05或P<0.01）。经丹参多酚酸盐48 mg/（kg·d）组治疗能够显著降低LN含量、提高MAP、降低HR（P<0.05或P<0.01）。经丹参多酚酸盐治疗能够明显改善肝硬化门静脉高压大鼠肝脏组织病变，以[48 mg/（kg·d）]组效果最为显著。[结论] 丹参多酚酸盐对大鼠肝纤维化门静脉高压具有一定的抑制作用，机制可能与丹参多酚酸盐能够降低氧化应激损伤。

Abstract:

[Objective] To investigate the inhibitoru effect of Salvianolate on liver fibrosis and portal hypertension in rats.[Methods] The liver fibrosis and portal hypertension model rats were made by peritoneal cavity injecting DMN, setting normal control group, model control group, Salvianolate[12, 24, 48 mg/(kg·d)] groups and Colchicine[0.1 mg/(kg·d)] group, 20 in each group. 6 weeks later, the content of ALT, AST, TBIL in serum were determined; the content of C-IV, PC-Ⅲ, LN, HA and the level of HYP in serum were determined; and the PVP, PVF, MAP, HR were detected; the histopathological changes of the hepatic tissue was observed by HE staining; the activity of SOD, CAT and the content of MDA in hepatic tissue were determined.[Results] After the Salvianolate[24, 48 mg/(kg.d)] were given for 6 weeks, the content of ALT, AST, TBIL, C-IV, PC-Ⅲ, HA, HYP in serum were significantly decreased (P<0.05 or P<0.01), the PVP, PVF were significantly decreased(P<0.05), the activity of SOD, CAT in hepatic tissue were significantly increased and the content of MDA were significantly decreased (P<0.05 or P<0.01). The content of LN in serum of Salvianolate[48 mg/(kg·d)] treated group was significantly decreased, the MAP was significantly increased and the HR was significantly decreased(P<0.05 or P<0.01). The hepatic histopathological changes of Salvianolate groups were significantly improved, especially the Salvianolate[48 mg/(kg·d)] group.[Conclusion] Salvianolate has inhibitory effects on liver fibrosis and portal hypertension in rats, which perhaps related to its effects of inhibiting the damage of oxidative stress.