JNK信号通路对乙醛刺激的大鼠肝星状细胞增殖的影响

Effects of JNK signal pathway on proliferation of hepatic stellate cells stimulated by acetaldehyde in rats

目的 :初步探讨JNK信号通路调控乙醛刺激的大鼠肝星状细胞 (HSC)增殖的分子机制。方法 :采用细胞培养 ,用c Jun氨基末端激酶 (c JunN terminalkinase ,JNK)特异性阻断剂 (SP60 0 12 5 )对乙醛刺激的HSC进行处理 ,以MTT比色法、Westernblot法检测细胞增殖和磷酸化JNK(p JNK)水平的变化 ,观察JNK通路对HSC增殖影响。 结果 :乙醛刺激后HSC增殖明显 ,同时JNK活性增强 ;使用SP60 0 12 5 (2 0、60ng/ml)后 ,明显抑制HSC增殖 (P <0 0 5 ) ,加大SP60 0 12 5浓度到 10 0ng/ml后 ,抑制作用更明显 (P <0 0 1) ;而p JNK水平也呈相应的降低 (P <0 0 5 )。 结论 :JNK活性变化与乙醛刺激的大鼠HSC的增殖具有相关性 ,提示JNK可能是调节HSC增殖的重要信号通路之一。

Objective: To explore the mechanism of JNK pathway regulating proliferation of hepatic stellate cells(HSC) stimulated by acetaldehyde. Methods: Cultured HSC stimulated by acetaldehyde were treated with SP600125, a special c - Jun N - terminal kinase(JNK) blocker. HSC proliferation was evaluated by MTT colorimetric assay; and variability of p - JNK was examined by Western blot. Then the effects of JNK pathway on HSC proliferation were observed. Results: Acetaldehyde increased obviously HSC proliferation and JNK activity, and HSC proliferation was inhibited remarkably by SP600125 at 20 or 60 ng·ml - 1(p<0 05). When the level of SP600125 reached to 100 ng·ml - 1, its inhibitive effect on HSC proliferation was more significant(p<0 01), and the expression of p - JNK decreased relatively(p<0 05). Conclusion: It is suggested that JNK has effects on proliferation of HSC stimulated by acetaldehyde and JNK maybe an important signal pathway regulating HSC proliferation.