| Objective: To investigate the effects and mechanism of Ginkgo-biloba extract761(EGb761) on improving hepatic microcirculation and inhibiting hepatic fibrosis, with HSC-T6 in vitro and sixty patients suffering from chronic hepatitis B as research objects.Methods: HSC-T6 cells were cultured with EGb761 at different dosages(1,10,100,500μg·ml-1) and without EGb761 as control.The expression of transforming growth factorβ1(TGF-β1) and connective tissue growth factor(CTGF) was determined by reverse transcnption-polymerase chain reaction(RT-PCR) after 24 hour and 48 hour culture. The cell cycles and proliferation were analyzed by flow cytometry an MTT.Sixty patients with chronic hepatitis B were randomly divided into two groups: EGb761 group(n=32) and control group (n=28). All cases underwent common treatment of protecting liver and the former added with EGb761 70mg, in drip qd for 4wk. liver functions, serum precollagen type III, IV-type collagen, hyaluronate(HA), laminin(LN) , transforming growth factor-β1 (TGF-β1) , ET-1 and platelet acting factor(PAF) levels Were measured before and after the treatment. Ten patients in each group were taken liver biopsy before and after the treatment. Pathological changes of liver were detected by HE staining. At the same time, the changes of hepatic sinusoidal microcirculation were analyzed by electron microscopy before and after treatments.Results: EGb761 down-regulated the expression of TGF-β1 and CTGF in HSC-T6 cells(p<0.01 or p<0.05), The effect of which was in a dose and time dependent manner. And it inhibited the proliferation of HSC-T6 cells.After treatment, the indexes of liver function showed obvious improvement in both groups, and there were no significant differences between two groups (p>0.05). Serum precollagen type III, IV-type collagen, hyaluronate(HA), laminin(LN) levels , plasma TGF-β1 , ET-1 and PAF levels in the treatment group decreased significantly(p<0.05 or p<0.01) ,but no difference was shown in those of the control group (p>0.05). After treatment, liver cirrhosis and tissue damages were improved significantly (p<0.05) in EGb 761 treatment group (inflammation score: 10.7±4.8;fibrosis score: 8.3±4.2) as compared with those in patients before treatment ( inflammation score: 15.7±6.3; fibrosis score; 11.9±6.2) and the controls (inflammation score: 14.2±6.6; fibrosis score; 11.5±5.6).Meanwhile, electron microscopy showed that liver microcirculatory dysfunction was improved obviously in EGb761 group after treatment in comparison with that before treatment, and the congregation of red cells in liver sinus(32 vs 56, P<0.01), the sedimentation of collagen in hepatic sinusoid and Disse space(23 vs 38, P < 0.05), the damage of hepatic sinusoidal endothelial cells( 41 vs 59, P<0.05) were markedly alleviated. However there is no difference before and after treatment in control group(P > 0.05) Conclusion: EGb 761 could exert the inhibitory effect on HSC-T6 cells by inhibiting the preliferation and down-regulating the expression of TGF-β1 and CTGF. EGb761 possesses significant role of anti-fibrosis on liver in patients with chronic hepatitis B possibly through inhibiting expression of TGF-β1, ET-1 and PAF and protecting hepatic sinusoidal endothelial cells from injury, inhibiting aggregation of blood cells, collagenous proliferation in sinusoid or Disse space and hepatic sinusoidal capilarization. |
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