DcR3 对肝纤维化动物模型的影响

目的:研究DcR3 基因对肝纤维化大鼠的预防性治疗的作用。方法:SPF 级健康雄性Wistar 大鼠30 只,体重范围180 ~220 g,随机分为3 组,每组10 只,分别为正常对照组、DcR3 基因预防性治疗组(1% DMN+DcR3 组)、造模组(1%DMN 组)。采用1%DMN 诱导大鼠肝纤维化模型,腹腔注射DcR3 质粒进行预防性干预。分别采用HE 染色和Masson 染色观察肝组织病理情况;qRT-PCR 和Western blot 法检测DcR3、Fas、FasL、-SMA 和TGF-1 的mRNA 和蛋白表达水平。结果:与模型组相比,DcR3 预防治疗组大鼠肝组织炎性细胞浸润及胶原类物质沉积有所改善;DcR3 基因可显著降低肝纤维化大鼠Fas、FasL、 SMA 和TGF-1 mRNA 和蛋白表达水平,DcR3 基因预防性治疗组与对照组和造模组有显著性差异(P<0.05);同时DcR3 基因预防性治疗组DcR3 mRNA 和蛋白表达水平显著升高(P<0.05)。结论:DcR3 基因可有效防治大鼠肝纤维化,其作用机制可能是DcR3 通过降低肝脏炎症反应,减少胶原类物质沉积,抑制 SMA 和TGF-1 表达,从而抑制HSC 活化;下调Fas和FasL 表达,抑制Fas/ FasL 途径诱导的肝细胞凋亡。

Effect of DcR3 on animal models of liver fibrosis

Objective:To study the preventive therapy effect on DcR3 gene on hepatic fibrosis rats.Methods: 30 healthy male Wistar rats were divided into 3 groups randomly which weight were 180-200 g:control group,DcR3 treatment group and hepatic fibrosis Group.Hepatic fibrosis was induced by 1% DMN intraperitoneal injection in hepatic fibrosis group and DcR3 treatment group.The plasmid transfected DcR3 was intraperitoneal injected in DcR3 group.All rats were killed at the end of 4th week.Then the livers pathology were used to make HE and Masson staining.The mRNA and protein level of DcR3,Fas,FasL, SMA and TGF-1 were measured by qRT-PCR and Western blot respectively.Results: Compared with model group,DcR3 improved the inflammatory cell infiltration and collagen deposition of liver in the rats of the DcR3 group.The mRNA and protein level of Fas,FasL, SMA and TGF-1 were significantly reduced in DcR3 group compared with hepatic fibrosis group(P<0.05).Meanwhile,the mRNA and protein levels of DcR3 was significant increase in DcR3 group (P<0.05).Conclusion: DcR3 could inhibit hepatic fibrosis efficiently by reducing the inflammatory response and collagen deposition,suppressing the expression of SMA and TGF 1,inhibiting HSC activin,down-regulating Fas/ FasL and suppressing the hepatocyte apoptosis induced by Fas/ FasL pathway.