研究表明，大鼠肝再生涉及细胞增殖和凋亡，受microRNA等调节。本课题组研究发现，大鼠肝再生中 miR-125a、miR-183、miR-199a和miR-429等4种microRNAs与促进大鼠肝细胞增殖和肝再生的miR-182表达趋势一致，且它们有共同的靶基因，因此推测，它们可能通过协同方式调控肝细胞增殖和肝再生。为验证上述推测，本项目拟首先检验它们的模拟物和抑制物对体外培养的大鼠（原代）肝细胞增殖的调节作用。然后从体外和体内两个方面、通过基因添加和干涉等方法上调和下调4种microRNA表达，检测这些干预对靶基因、对肝细胞增殖/凋亡相关基因和蛋白表达、对肝细胞增殖/凋亡、对再生肝生长等的影响，用网络原理和方法解析它们调控肝细胞增殖和肝再生的途径和方式，为揭示肝再生机制、建立治疗和预防肝病方法奠定基础。

Rat liver regeneration (LR) involves cell proliferation and apoptosis, and is regulated by microRNA.Our previous study showed that miR-182 promoted rat hepatocyte proliferation and LR, and the trend of the relative expression of miR-125a, miR-183, miR-199a and miR-429 in rat LR were in accordance with that of miR-182, and the five miRNAs share common target genes. Therefore, we speculated that they might synergistically regulate rat primary cultured hepatocyte proliferation and rat LR. To verify the speculation, we will firstly study the role of the mimic and inhibitor of four microRNAs in rat primary cultured hepatocyte. And then we will up-regulate and down-regulate the expression of four microRNAs in vitro and in vivo by gene addition and RNA interference, and detect the effect of these interventions on the expression changes of the target genes, and on the expression changes of genes and proteins related to hepatocytes proliferation and apoptosis, and on hepatocytes proliferation and apotosis and liver regeneration. Finally, we will parse the ways and means of four microRNAs in regulating the hepatocytes proliferation and LR by network principle and method, which may provide a theoretical basis for revealing the mechanism of rat LR and establishing the prevention and treatment strategies of liver diseases.