NHE-1与肝星状细胞增殖的关系及姜黄素对其的影响

目的:研究NHE-1与肝星状细胞增殖的关系及姜黄素对其的影响, 初步探讨肝纤维化的形成机制.方法:选择肝星状细胞系作为体外研究对象,用不同浓度(1、10、20 μmol/L)的姜黄素处理大鼠肝星状细胞; 以MTT比色法测定肝星状细胞的增殖; 酶联免疫吸附法(ELISA)测定Ⅰ型胶原含量, RT-PCR法检测肝星状细胞Na+/H-泵(NHE-1 mRNA)的表达.结果:各浓度姜黄素可明显下调肝星状细胞NHE-1 mRNA表达(0.6401±0.0063, 0.2391±0.0039, 0.1437±0.0044 vs 0.7214±0.0155,P <0.05), 降低培养上清液中Ⅰ型胶原的水平(199.40±16.22, 182.37±14.72, 169.91±15.80 ng/mg pro vs 216.35±17.19 ng/mg pro,P <0.05), 抑制肝星状细胞的增殖, 并呈剂量依赖性.结论:姜黄素可能通过调控肝星状细胞NHE-1mRNA的表达来抑制HSC的增殖及Ⅰ型胶原的合成等机制, 从而抑制肝纤维化的形成.

Influence of curcumin on NHE-1 mRNA and hepatic stem cell proliferation and their correlations

AIM: To study the relationship between the mRNA of NHE-1 and the proliferation of hepatic stellate cells (HSCs) and the influence of curcumin on them. METHODS: Hepatic stellate cell lines (HSC-T6) were incubated with different concentrations (1, 10, 20 μmol/L) of curcumin for 24 h. The proliferation of hepatic stellate cells was measured by MTT. The content of collagen I was measured by ELISA. The mRNA of NHE-1 was examined by RT-PCR. RESULTS: Curcumine down-regulated the expression of NHE-1 mRNA (0.6401 ± 0.0063, 0.2391 ± 0.0039, 0.1437 ± 0.0044 vs 0.7214 ± 0.0155, all P < 0.05), decreased the levels of collagen I (199.40 ± 16.22, 182.37 ± 14.72, 169.91 ± 15.80 ng/mg pro vs 216.35 ± 17.19 ng/mg pro, all P < 0.05) and lowered the number of proliferating HSCs in a concentration dependent way. CONCLUSION: These results suggest that curcumine can prevent hepatic fibrosis via inhibiting proliferation and collagen I production of HSCs, which may be partly related to its regulative effect on the expression of NHE mRNA gene.