苦参碱抑制小鼠腹膜巨噬细胞纤维化细胞因子的产生和作用

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。

Matrine inhibits production and actions of fibrogenic cytokines released by mouse peritoneal macrophages

AIM: To study the effects of matrine (Mat) on production and actions of fibrogenic cytokines from mouse peritoneal macrophages. METHODS: Mouse peritoneal macrophages were primed with calcimycin 1 micromol/L for 8 h then elicited by lipopolysaccharides (LPS) 100 microg/L for 6 h to induce fibrogenic cytokines. Proliferative and collagen stimulating activity in the macrophage culture supernatants was determined by crystal violet staining assay and 3H]-proline incorporation assay using rat hepatic stellate HSC-T6 cell or mouse fibroblast NIH3T3 cell. Transforming growth factor beta (TGFbeta) activity was measured by 3H]-thymidine incorporation assay using Mv-1-Lu mink lung epithelial cell. RESULTS: Mat (0.5-2 mmol/L) was shown to significantly inhibit LPS-induced collagen stimulating activities and TGFbeta production (P < 0.01) whereas did not inhibit proliferative activities induced by macrophages. Macrophage conditioned medium (MCM)-driven proliferation and collagen synthesis of HSC-T6 cells as well as NIH3T3 cells were attenuated by Mat (0.5-2 mmol/L) in a concentration-dependent manner. CONCLUSION: Antifibrotic effects of Mat on hepatic stellate cells may be related to reduction of fibrogenic cytokine production and blockade of their actions.