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目的:研究体外苦参碱对HSC-T6大鼠储脂细胞和NIH3T3成纤维细胞增殖和胶原合成的影响,以及体内对四氯化碳诱导的大鼠肝纤维化的影响。方法:细胞增殖和胶原合成分别采用结晶紫染色法和[~3H]脯氨酸掺入法。肝纤维化评价以血清透明质酸和肝中羟脯氨酸含量为指标。结果:苦参碱(1~2mmol·L~(-1))显著减少血清刺激的HSC-T6细胞以及NIH3T3细胞增殖和胶原合成;苦参碱(0.25~2mmol·L~(-1))浓度依赖地抑制血小板源生长因子(PDGF)促HSC-T6细胞增殖以及抑制转化生长因子β_1(TGF-β_1)促胶原合成的作用。体内苦参碱(50,100mg·kg~(-1))均能显著降低血清透明质酸和肝脏羟脯氨酸水平。结论:苦参碱阻断PDG和TGF-β_1的作用,抑制储脂细胞增殖和胶原合成可能是其抗肝纤维化作用的机制之一。
Objective: To investigate the effect of matrine on the proliferation and collagen synthesis of HSC-T6 rat fat-storing cells and NIH3T3 fibroblasts, and the effect of matrine on rat liver fibrosis induced by carbon tetrachloride. METHODS: Crystal violet staining and [~3H]proline incorporation were used for cell proliferation and collagen synthesis, respectively. Liver fibrosis was assessed using serum hyaluronic acid and liver hydroxyproline content as indicators. RESULTS: Matrine (1~2 mmol·L-1) significantly reduced the proliferation and collagen synthesis of serum-stimulated HSC-T6 cells and NIH3T3 cells; matrine (0.25-2 mmol·L-1) concentration Dependent inhibition of platelet-derived growth factor (PDGF) promotes HSC-T6 cell proliferation and inhibition of transforming growth factor-β 1 (TGF-β_1)-induced collagen synthesis. In vivo matrine (50,100 mg·kg -1 ) could significantly reduce serum hyaluronic acid and hepatic hydroxyproline levels. Conclusion: The effects of matrine blocking PDG and TGF-β_1, inhibiting the proliferation and collagen synthesis of fat-storing cells may be one of the mechanisms of anti-fibrosis effects.