LY294002在外源性H_2S预处理肝纤维化大鼠肝星状细胞增殖、凋亡中的作用

The role of LY294002 in cell proliferation and apoptosis when exogenous H_2S post-processing of liver fibrosis rat hepatic stelate cells

目的探讨硫化氢(hydrogen sulfide,H2S)通过PI3K/Akt信号通路对大鼠肝星状细胞增殖、凋亡的调节作用。方法 MTT法分别检测NaHS(H2S的供体)和PI3K/Akt信号通路的特异性抑制剂LY294002对大鼠肝星状细胞(HSC-T6)的增殖、增殖抑制率的影响;采用流式细胞技术检测药物的有效浓度对HSC-T6凋亡的调节。结果低浓度(50μmol/L)的NaHS能够明显促进HSC-T6的增殖(F=955.949,P=0.000),LY294002可抑制HSC-T6的增殖,伴随药物浓度的升高细胞存活率降低(P<0.05),并诱导HSC-T6的凋亡,而二者联合应用诱导HSC-T6凋亡作用增强。结论 H2S可能通过PI3K/Akt信号通路促进HSC-T6的增殖,但对肝星状细胞的凋亡抑制作用并不显著,H2S可协同LY294002共同诱导HSC-T6细胞的凋亡。

Objective To discuss proliferation and apoptosis regulation effect of the hydrogen sulfide （H2S） through the PI3K/Akt signal pathway to rat hepatic stellate cell . Methods The growth inhibition of HzS and LY294002 alone or in combination on HSC-T6 cells was detected by MTT assay; Effects of H2S and LY294002 alone or combination with phosphatidylinositol-3-kinases （PI3K） inhibitor LY294002 in a drug effective concentration on apoptosis regulation of HSC-T6 cells were detected by flow cytometry technology（FCM）. Results The Naris in low concentration（50 μmol/L） could promote the HSC-T6 cells proliferation （P 〈 0.05 ）, LY294002 could inhibit HSC-T6 cells proliferation （P 〈 0.05 ）. With the rising of drug concentration, the cells survival rate reduced, also induced the HSC-T6 cells apoptosis, moreover, the apoptotic ratio of HSC-T6 cells was increased by H2S in combination with LY294002. Conclusion The H2S may promote the hepatic stellate cell proliferation through the PI3K/Akt signal path, but apoptosis effect of hepatic stellate cell was not significant; and in another aspect, H2S cooperated with LY294002 induced HSC-T6 cells apoptosis.