[Effects of Qinggan Huoxue Recipe and its separated recipes on urokinase-type plasminogen activator and plasminogen activator inhibitor-1 fibrinolytic system in rats with alcoholic liver fibrosis].
OBJECTIVE
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Chen
Jun-ming
JM
Institute of Digestive Diseases and Department of Gastroenterology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
Wang
Lei
L
Liu
Tao
T
Xing
Lian-jun
LJ
Zheng
Pei-yong
PY
Ji
Guang
G
D000818:Animals; D002251:Carbon Tetrachloride; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D000431:Ethanol; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy*; D008108:Liver Diseases, Alcoholic / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008517:Phytotherapy; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism*
D004365:Drugs, Chinese Herbal; D017395:Plasminogen Activator Inhibitor 1; C527179:qinggan huoxue; D000431:Ethanol; D002251:Carbon Tetrachloride; D014568:Urokinase-Type Plasminogen Activator