不同治则中药复方对胆汁淤积性肝纤维化大鼠uPA纤溶途径的调控

Regulate Effects of Chinese Medicine Complex Prescriptions on uPA of Cholestasis-induced Liver Fibrosis Rat

目的:研究不同治则中药复方对胆汁淤积性肝纤维化大鼠uPA-纤溶酶-MMP级联反应纤溶途径的调控作用。方法:SD雄性大鼠60只随机分为假手术组和造模组,造模组1周后随机分为模型组、二至丸组、失笑散组及合方组。各治疗组分别给予相应药物灌胃,模型组和假手术组给予等量生理盐水灌胃,4周末处死大鼠。观察一般情况、肝功能(ALT、AST、ALP、TB il)、肝组织病理、W estern印迹法检测肝组织uPA蛋白表达、ELISA法检测肝组织MMP-2、MMP-9的表达。结果:与模型组比较,3个复方均能降低胆汁淤积性肝纤维化大鼠血清ALP、ALT、AST水平(P<0.01),失笑散及合方能降低TB il(P<0.01);合方改善ALP、ALT优于两个复方。3个复方均能不同程度地减轻模型大鼠肝纤维化程度(P<0.01),合方优于两个复方。3个复方均能显著提高胆汁淤积性肝纤维化大鼠uPA、MMP-2、MMP-9的表达(P<0.01),合方对上述环节的调控优于两个复方。结论:不同治则中药复方均能改善胆汁淤积性肝纤维化大鼠肝功能,减轻纤维化程度,合方作用优于两个复方,其机制可能与通过上调uPA、MMP-2、MMP-9,从而调控uPA-纤溶酶-MMP级联反应纤溶途径有关。

Objective： To study the regulate effects of the Chinese medicine complex prescriptions on cholestasis - induced liver fibrosis rats urokinase type plasrninogen activator （uPA）. Methods ： Sixty male Sprague - Dawley （SD） rats weighing（ 260 ＋ 20）g were randomly divided into 2 groups：Sham - operation group and making model group. Using bile duct ligation method to make the model of eholestasis - induced liver fibrosis. One week later after the operation ,the making model group rats were randomly divided into four groups：untreated group,Erzhi pill group, Shixiao powder group and Erzhipill compound with Shixiaosan（ECS） group. Each medicine intervention group was given corresponding medicine by intragastrie administ ration. Sham - operation group and model group were given sodium chloride with equal dosage. At the end of 4th week, all of the rats were sacrificed and sampled. General state of health, hepatic function （ alanine aminotransferase, ALT; aspartate aminotransferase, AST; alkaline phosphatase, ALP; total bilirubin, TBil） and pathological histology of hepatic tissue were recorded and measured. Detected uPA with Western blotting and Matrix Metalloproteinase （MMP） -2, MMP- 9with enzyme linked immunosorbent assay （ELISA）. Results ：The serum of ALP, ALT and AST level of three Chinese medicine complex prescriptions groups rats and the serum level of TBil of Shixiaosan and ECS group rats were decreased comparing with untreated group （ P 〈 0.01 ）. ECS was better than Complex prescriptions in ALP and ALT. All of three complex prescriptions could release liver fibrosis at some extent （P 〈0.01 ） ,but ECS was more obviously than other Complex prescriptions. The uPA, MMP -2, MMP- 9 expression significantly increased in above three Chinese medicine complex prescription group compared to untreated group （ P 〈 0. 01 ）, ECS group was the highest. Conclusion ：Chinese mdeicine complex prescriptions （Erzhiwan, Shixiaosan and ECS） can improve the Hepatic function of cholestasis - induced liver fibrosis rats, palliate the level of hepatic fibrosis. ECS was better than other Complex prescriptions. The mechanism was probably to regulate the uPA.