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研究维生素E(VitE)和不同剂量硒(Se)对肝纤维化大鼠肝星状细胞(HSC)中金属蛋白酶1组织抑制剂(TIMP-1)mRNA表达的影响,从分子水平揭示VitE和Se对肝纤维化的治疗作用及其机制。方法:用40%CCL4制备大鼠肝纤维化模型,并在饲料中补充VitE和不同剂量的Se进行营养干预。应用HE常规染色和Masson三色胶原染色对肝组织切片行组织病理学检查;应用逆转录聚合酶链反应(RT-PCR)技术,以β肌动蛋白(actin)作为内对照,检测HSC中TIMP-1mRNA表达的变化。结果:VitE补充组(250mg/kg食物)和低Se补充组(0.2mg/kg食物)大鼠与病理造模组相比,肝纤维化程度显著减轻,HSC中TIMP-1mRNA的表达显著降低(P<0.05);而较高剂量Se(1.0mg/kg食物)则使HSC中TIMP-1mRNA的表达呈上升趋势(与病理造模组相比,P>0.05)。结论:VitE和适当剂量的Se能显著减轻大鼠肝纤维化程度,下调HSC中TIMP-1mRNA的表达;而过高剂量的Se则无上述作用。
To investigate the effects of VitE and Se on TIMP-1 mRNA expression in hepatic stellate cells (HSC) of rats with hepatic fibrosis, VitE and Se Therapeutic effect on liver fibrosis and its mechanism. Methods: The rat model of hepatic fibrosis was prepared with 40% CCL4, and VitE and different doses of Se were supplemented in the diet for nutrition intervention. Histopathological examination of hepatic tissue sections was performed by HE staining and Masson trichrome staining. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of TIMP in HSC using actin as internal control -1 mRNA expression changes. Results: Compared with the model group, the levels of liver fibrosis in VitE supplementation group (250mg / kg food) and low Se supplementation group (0.2mg / kg food) significantly reduced the expression of TIMP-1mRNA in HSC (P <0.05), while the higher dose of Se (1.0mg / kg food) increased the expression of TIMP-1mRNA in HSC (P> 0.05). Conclusion: VitE and appropriate dose of Se can significantly reduce the degree of hepatic fibrosis in rats and down-regulate the expression of TIMP-1 mRNA in HSC. However, excessive doses of Se do not have the above effects.