PD98059对乙醛刺激的大鼠肝星状细胞增生的影响

Effects of PD98O59 on proliferation of rat cultured hepatic stellate cells stimulated by acetaldehyde

目的:探讨特异性MEK1阻断剂PD98059对乙醛刺激的肝星状细胞(hepatic stellate cell,HSC)增生及其细胞增生核抗原表达的影响。方法:用PD98059对乙醛刺激的HSC进行处理,分别以MTT比色、免疫细胞化学法检测细胞增生及其细胞增生核抗原表达。结果:PD98059在20μmol/L时即对HSC增生出现抑制作用(P<0.05,C组0.109±0.20 vs B组0.146±0.030),50、100μmol/L时抑制作用逐渐增强(P<0.05,D、E组0.081±0.010、0.056±0.020 vs B组0.146±0.030);HSC中PCNA表达也随PD98059剂量增加而减弱(P<0.05,C、D、E组0.62±0.09、0.47±0.04、0.34±0.04 vs B组0.74±0.05)结论:PD98059对HSC增生及细胞增生核抗原表达具有抑制作用,提示Erk信号传导通路是调控肝星状细胞增生的重要通道。

AIM: To study the effects of PD98059, the specific blocking agent of MEK_1, on the proliferation of hepatic stellate cells and expression of Proliferating Cell Nuclear Antigen in rat hepatic stellate cells (HSC). METHODS: HSC stimulated by acetaldehyde were cultured. The cell growth was evaluated by MTT colorimetric assay. Proliferating cell nuclear antigen (PCNA) was examined by immunocytochemical staining. RESULTS: PD98059 of 20 μmol/L had an inhibitory effect on proliferation of HSC (P<0.05, 0.109±0.020 vs 0.146±0.030), which was more obvious when cells exposed to PD98059 at 50 and 100 μmol /L (P<0.05, 0.081±0.010, 0.056±0.020 vs 0.146±0.030), and the expression of PCNA also showed a descending tendency with the increase of PD98059 con- centration (P<0.05, 0.62±0.09, 0.47±0.04, 0.34±0.04 vs 0.74±0.05) CONCLUSION: PD98059 inhibits proliferation of HSC and expression of PCNA, which is correlated with the decreased activity of PCNA.