Effect Of Vitamin C And E On Proliferation And Production Of Tissue Inhibitor Of Matrix Metalloprotease-1of Hepatic Stellate Cell Induced By Leptin

Objective:The key link of development of liver fibrosis is that activated hepatic stellate cells (HSC) produce large amounts of collagen, resulting in imbalance of collagen deposition and degradation. Leptin is a strong profibrosis factor, which can lead to elevate oxidative stress of HSC, further cause proliferation of HSC and increase expression of tissue inhibitor of matrix metalloproteinase-1(TIMP-1). Vitamin C and E are strong antioxidants, and impact of vitamin C and E on leptin-induced HSC proliferation and secretion of TIMP-1, as well as impact of that on production of reactive oxygen species (ROS) in HSC, was observed, and their anti-fibrosis mechanism were explored.Methods:Sulforhodamine B assay was performed to test the inhibitory effect of vitamin C and E on proliferation of HSC induced by leptin, the detection probe of ROS2,7-dichlorfiuorescein-diacetate was to detect impact of vitamin C and E on production of ROS in HSC induced by leptin, enzyme-linked immunosorbnent assay was used to detect impact of vitamin C and E on production of TIMP-1induced by leptin.Results:The inhibitory effect of vitamin C at concentrations of100μmol/l,200μmol/1and400μmol/1had statistically significant differences compared with leptin group on proliferation of HSC induced by leptin (P<0.05), and there were statistically significant differences between concentrations (P<0.05). The inhibitory effect of vitamin E at concentrations of80μmol/1,160μmol/1and320μmol/1had statistically significant differences compared with vehicle plus leptin (P<0.05). The highest concentrations combined, compared with single group, had more inhibition effective on HSC proliferation induced by leptin (P<0.05). At the same time these concentration groups of vitamin C and E were able to inhibit ROS production induced by leptin, the difference was statistically significant (P<0.05). The concentration groups of vitamin C and vitamin E could inhibit the production of TIMP-1induced by leptin (P<0.05), there existed statistically significant differences between concentration groups (P<0.05), compared with single group, the highest concentrations combined group had more inhibition effective (P<0.05).Conclusion:Antioxidants vitamins C and E may inhibit proliferation of HSC and TIMP-1production by inhibiting oxidative stress induced by leptin.