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目的:研究苦参碱对小鼠腹腔巨噬细胞释放纤维化细胞因子以及对巨噬细胞条件培养基(MCM)促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。方法:巨噬细胞先后用卡西霉素1μmol/L和脂多糖100μg/L刺激诱导产生纤维化因子。细胞上清中促细胞增殖活性和促胶原合成活性分别用结晶紫染色法和[~3H]-脯氨酸掺入法测定。转化生长因子β活性采用貂肺上皮MV-l-Lu细胞增殖抑制法测定。结果:苦参碱(0.5-2mmol/L)显著抑制LPS诱导的促胶原合成活性和TGFβ的产生,但不能抑制巨噬细胞产生促细胞增殖活性;苦参碱还能剂量依赖地抑制MCM诱导的HSC-T6细胞以及NIH3T3细胞增殖和胶原合成。结论:苦参碱抗肝纤维化作用与抑制巨噬细胞纤维化因子的产生和阻断其作用有关。
Objective: To study the effects of matrine on the release of fibrotic cytokines from mouse peritoneal macrophages and the effects of macrophage conditioned medium (MCM) on the proliferation and collagen synthesis of HSC-T6 rats’solic fat cells and NIH3T3 fibroblasts. METHODS: Macrophages were stimulated with 1 μmol/L of kazimycin and 100 μg/L of lipopolysaccharide to induce fibrogenic factors. The activity of promoting cell proliferation and the activity of promoting collagen synthesis in the cell supernatant were determined by crystal violet staining and [~3H]-proline incorporation. The activity of transforming growth factor β was determined using the proliferation inhibition method of MV-l-Lu cells in silicosis epithelium. RESULTS: Matrine (0.5-2 mmol/L) significantly inhibited LPS-induced collagen synthesis activity and TGFβ production, but could not inhibit the production of proliferative cells by macrophages; matrine also dose-dependently inhibited MCM-induced HSC-T6 cells and NIH3T3 cell proliferation and collagen synthesis. CONCLUSIONS: Anti-hepatic fibrogenesis of matrine is associated with inhibition of the production of macrophage fibrogenic factors and its blocking effect.