| Objective To evaluate the Ginkgo biloba Extracts (GbE) in rats with CCl4-induced hepatic fibrosis and the influence on cyclooxygenase-2 (COX-2), thromboxane B2(TXB2), 6-Ketoprostaglandin F1 alpha (6-K-PGF1α), to explore the effects of GbE on rats with CCl4-induced hepatic fibrosis and its possible mechanism.Methods Sixty male SD rats were randomly divided into the normal control group(10 rats),the model group(10 rats),the GbE high dose group(10 rats), the GbE moderate dose group(10 rats), the GbE low dose group(10 rats) and the Fufang Biejia Ruangan Pian group(10 rats).Rats in normal control group were given subcutaneous injection of olive oil, and all the other rats were given subcutaneous injection of 40% carbon tetrachloride (3ml/kg, twice every week for 6 weeks and the dosage double for the first time).The rats of the three GbE groups were respectively given 200mg/kg, 100mg/kg,50mg/kg of GbE by daily gavage. The rats of Fufang Biejia Ruangan Pian treatment group were given Fufang Biejia Ruangan Pian of 1g/kg by daily gavage for 6 weeks. Rats in normal control group and the model group were given distilled water according to the same volume by daily gavage at the same time. At the end of the sixth week, all rats were sacrificed. The pathological changes of liver were observed with HE and Masson staining; The serum ALT, AST and ALP levels were evaluated by automatic biochemical mater; the expression of COX-2 mRNA was detected by fluorescent in situ hybridization; The contents of plasma TXB2 and 6-K-PGF1αwere measured by Radioimmunoassay; The protein expressions of COX-2, a-SMA and Type I collagen were detected by immunohistochemistry.Results①The degrees of liver inflammation and hepatic fibrosis of the rats in the model group were higher than that in the normal control group(P<0.01),and The degrees of liver inflammation and hepatic fibrosis of the rats in the GbE and Fufang Biejia Ruangan Pian groups were significantly reduced(P<0.01,P<0.05);(2)The serum levels of ALT,AST and ALP of the rats in the model group were higher than that in the normal control group(P<0.01). The serum levels of ALT and AST of the rats in the GbE and Fufang Biejia Ruangan Pian groups were lower than that in the model group (P<0.01). The serum levels of ALP of the rats in the GbE high dose group, the GbE moderate dose group and the Fufang Biejia Ruangan Pian groups were also lower than that in the model group(P<0.01,P<0.05);③The hepatic a-SMA and Type I collagen protein expression of the rats in the model group were higher than that in the normal control group(P<0.01) and The hepatic a-SMA and Type I collagen protein expression of the rats in the GbE and Fufang Biejia Ruangan Pian groups were significantly reduced(P<0.01,P<0.05);④The mRNA and protein expressions of hepatic COX-2 of the rats in the model group were higher than that in the normal control group(P<0.01,P<0.05) and The mRNA and protein expressions of hepatic COX-2 in the GbE and Fufang Biejia Ruangan Pian groups were significantly reduced(P<0.05);⑤The content of TXB2 and the rate of TXB2/6-K-PGF1αin the model group were higher than that in the normal control group(P <0.01,P<0.05) and The content of TXB2 and the rate of TXB2/6-K-PGF1αin the GbE and Fufang Biejia Ruangan Pian groups were significantly reduced(P<0.01,P<0.05). The content of 6-K-PGF1αshowed no significant difference among the six groups(P>0.05).⑥The expression of COX-2 protein is positive correlation with the degree of liver inflammation, hepatic fibrosis, a-SMA and Type I collagen(Respectively, the values of r are 0.918,0.510,0.636,0.439, P<0.01).Conclusions①GbE can protect the hepatic cells, improve liver function and remarkably reduce the hepatic tissue inflammation of the rats with CCl4-induced liver fibrosis.②Increase of the expression of COX-2 and the activation of HSC exist in rats with CCl4-induced liver fibrosis.③GbE could obviously depress the expression of COX-2 and inhibit the activation of HSC, and it may be one important mechanism for GbE to treat hepatic fibrosis.
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