Chen Jun-ming, Wang Lei, Liu Tao, Xing Lian-jun, Zheng Pei-yong, Ji Guang
Institute of Digestive Diseases and Department of Gastroenterology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
Zhong Xi Yi Jie He Xue Bao. 2009 Jul;7(7):642-50. doi: 10.3736/jcim20090708.
To study the action mechanisms of Qinggan Huoxue Recipe (QGHXR), a compound traditional Chinese herbal medicine, and its separated recipes by observing their effects on expressions of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) in rats with alcoholic liver fibrosis (ALF).
A total of 150 SD rats were divided into three groups: blank group, carbon tetrachloride (C(4)) group and ALF-inducing group. Rats in the ALF-inducing group were administered with a mixture diet (56% alcohol 10 mL/kg, corn oil 2 mL/kg, pyrazole 25 mg/kg) once daily and intraperitoneally injected with 0.3 mL/kg 25% solution of C(4) in olive oil twice weekly. The C(4) group was intraperitoneally injected with equal volume of C(4) and olive oil as the ALF-inducing group and ingested normal saline (12 mL/kg per day). The blank group was intraperitoneally injected with and ingested saline in equal volumes of the above. At the end of the eighth week, the survived rats in the ALF-inducing group were divided into four subgroups: untreated group, QGHXR group, Qinggan Recipe (QGR) group and Huoxue Recipe (HXR) group. The three treated groups were given corresponding drugs respectively (4.75, 1.5, 3.25 g/kg). The blank group, CCl(4) group and untreated group were given normal saline in equal volume (5 mL/kg per day). All rats were anaesthetized and killed at the end of the twelfth week. The activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum were analyzed. Pathological changes in liver tissues were observed by hematoxylin and eosin staining and Masson staining. The expressions of uPA and PAI-1 were evaluated with Western blotting, immunofluorescence, and real-time polymerase chain reaction.
There existed obvious liver fibrosis in liver tissues in the untreated group as compared with the blank group (P<0.01), and the activities of ALT and AST and the expressions of uPA and PAI-1 also increased in the untreated group. QGHXR and its separated recipes could improve the degree of liver fibrosis (P<0.01). QGHXR and its separated recipes could degrade the activity of ALT as compared with the untreated group; QGHXR and its separated recipes advanced the expression of uPA, and decreased the expression of PAI-1 significantly as compared with the untreated group. The effect of QGHXR was the best among the three recipes.
QGHXR and its separated recipes may improve ALF in rats by decreasing the expression of PAI-1 and advance the expression of uPA. The effect of QGHXR is the best among them.
通过观察清肝活血方（QGHXR）及其拆方对酒精性肝纤维化（ALF）大鼠尿激酶型纤溶酶原激活剂（uPA）和纤溶酶原激活剂抑制剂-1（PAI-1）表达的影响，探讨其作用机制。
将150只SD大鼠分为三组：空白组、四氯化碳（C₄）组和造模组。造模组大鼠每日给予混合饲料（56%乙醇10 mL/kg、玉米油2 mL/kg、吡唑25 mg/kg），每周两次腹腔注射0.3 mL/kg 25% C₄橄榄油溶液。C₄组腹腔注射与造模组等体积的C₄和橄榄油，并给予生理盐水（12 mL/kg·d）。空白组腹腔注射和灌胃与上述等体积的生理盐水。第8周结束时，将造模组存活的大鼠分为四组：未治疗组、清肝活血方组、清肝方（QGR）组和活血方（HXR）组。三个治疗组分别给予相应药物（4.75、1.5、3.25 g/kg）。空白组、CCl₄组和未治疗组给予等体积生理盐水（5 mL/kg·d）。第12周结束时，将所有大鼠麻醉处死，检测血清丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）活性，苏木精-伊红染色和Masson染色观察肝组织病理变化，采用蛋白质免疫印迹法、免疫荧光法及实时聚合酶链反应法检测uPA和PAI-1的表达。
与空白组相比，未治疗组肝组织存在明显肝纤维化（P<0.01），未治疗组ALT和AST活性及uPA和PAI-1表达也升高。清肝活血方及其拆方可改善肝纤维化程度（P<0.01）。与未治疗组相比，清肝活血方及其拆方可降低ALT活性；清肝活血方及其拆方可上调uPA表达，显著下调PAI-1表达。清肝活血方的作用最佳。
清肝活血方及其拆方可通过下调PAI-1表达、上调uPA表达改善大鼠酒精性肝纤维化，其中清肝活血方效果最佳。
