[Study on the inhibitive effect of Astragalus Injection solution on hepatic fibrosis in rats].
OBJECTIVE
To investigate the effect of Astragalus Injection solution on rat hepatic stellate cells (HSC) and hepatic fibrosis.


METHODS
HSCs of rats were incubated with various concentrations of Astragalus Injection solution (0 mg/ml, 25 mg/ml, 50 mg/ml, 100 mg/ml, 200 mg/ml, 400 mg/ml) for 24, 48 and 72 hours. Cell proliferation was detected with 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphennyltetrazolium bromide (MTT) colorimetric assay. Cell cycle was detected with flow cytometry. Cell apoptosis was detected with acridine orange/ethidium bromide (AO/EB) fluorescent staining and flow cytometry. In vivo, rats were randomly allocated into a normal control group, a model control group and an Astragalus Injection group. Astragalus Injection (800 mg.kg-1.d-1) was administered to rats of the Astragalus Injection group. Rats of the model control group received saline. Serum concentrations of hyaluronic acid (HA) and laminin (LN), hepatic tissue activity of superoxide dismutase (SOD), and hepatic tissue contents of malondialdehyde (MDA) were measured in these groups at 8 weeks. Hepatic tissue expression of LN was assessed by using immunohistochemistry. The pathological changes of hepatic tissues were examined by hematoxylin-eosin (HE) and van Gieson (VG) staining of their histological slides.


RESULTS
In vitro, compared with the 0 mg/ml group, the proliferation of HSCs in other concentration groups was significantly inhibited by Astragalus Injection solution in a dose and time dependent manner, the cell proliferation cycle of HSCs was blocked in the G2-M phase, there was no apoptosis of HSCs in AO/EB fluorescent staining and flow cytometry. In vivo, compared with rats of the model control group, the rats of the Astragalus Injection solution treated group had remarkably decreased serum HA and LN levels (114.3+/-25.6) microg/L vs (85.6+/-37.3) microg/L and (78.8+/-11.7) microg/L vs (66.8+/-17.6) microg/L, P < 0.05, and liver MDA level (3.7+/-0.4) micromol/g protein vs (2.4+/-0.2) micromol/g protein, P < 0.01, but had increased activity of liver SOD (49.6+/-5.7) NU/mg protein vs (75.9+/-5.9) NU/mg protein, P < 0.01. Microscopic studies revealed that the livers of rats receiving Astragalus Injection solution showed decreases in fibrosis and in expression of LN.


CONCLUSIONS
Astragalus Injection solution has an inhibitive effect on experimental hepatic fibrogenesis. The mechanisms of its effects might possibly be associated with its antioxidant activity, expression of decreasing LN and its inhibition of HSCs proliferation.
Zhou
Xian
X
Department of Gastroenterology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
Dai
Li-li
LL
Jia
Li-ping
LP
Zheng
Yuan-yi
YY
Wang
Wen-bing
WB
D000818:Animals; D027885:Astragalus propinquus; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005260:Female; D022781:Hepatocytes / Q000473:pathology; D007267:Injections; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008517:Phytotherapy; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D004365:Drugs, Chinese Herbal