肝再生增强因子抑制肝非实质细胞TGF-β_1表达的意义

Significance of inhibitory effect of augmenter of liver regeneration on expression of TGF-β_1 in nonparenchymal cells of liver

目的探讨肝再生增强因子(ALR)促进受损肝细胞增殖的机制。方法采用免疫组化方法检测ALR对肝星状细胞和Kupffer细胞(KC)中TGF-β1表达的影响,Westernblot法检测ALR对肝星状细胞表达TGF-β1的影响,细胞增殖试验(MTT法)观察经ALR刺激的大鼠肝星状细胞条件培养液(ICCM)、KC条件培养液(KCCM+)对受损肝细胞增殖的影响以及ALR对TGF-β1抑制受损肝细胞增殖的作用。结果经ALR刺激后肝星状细胞和KC中TGF-β1免疫反应阳性信号减弱,Westernblot显示ALR可抑制肝星状细胞表达TGF-β1。受损肝细胞经ICCM和KCCM刺激后增殖明显。ALR可拮抗TGF-β1对受损肝细胞增殖的抑制作用。结论ALR可能通过抑制肝星状细胞和KC表达TGF-β1来促进受损肝细胞增殖。

Objective To Investigate the mechanism of augmenter of liver regeneration （ALR） in promoting proliferation of damaged hepatocyte. Methods The inhibitory effects of ALR on the expression of TGF-β1 in hepatic stellate cell and Kupffer cell were studied by irnmtmohistochemistry and Western blot. The effects of hepatic stellate cell （Ito cell） conditioned medium （ICCM＋） and Kupffer cell conditioned medium （KCCM＋） prepared by treatment of using augmenter of liver regeneration （ALR） on damaged hepatocy-tes proliferation were studied by MTT. The antagonistical role of ALR on TGF-β1, which inhibited damaged hepatocyte proliferation was investigated by MTT determination. Results Immunoreactive positive signal of TGF-β1 in hepatic stellate cell and Kupffer cell stimulated by ALR were decreased. Immunolabeling of TGF-β1 in hepatic stellate cell stimulated by ALR was weakened. The proliferation of damaged hepatocytes was increased significantly by administration of ICCM and KCCM. ALR could reverse the inhibitory role of TGF-β1 on the proliferation of damaged hepatocyte. Conclusion ALR can promote proliferation of injured hepatocyte indirectly by inhibiting expression of TGF-β1 in hepatic stellate cell and Kupffer cell.