沙鼠非酒精性脂肪性肝病形成中氧化应激及细胞因子的变化及意义

Dynamic changes of oxidative stress and cytokines in gerbils with nonalcoholic fatty liver disease and their significance

目的研究长爪沙鼠非酒精性脂肪性肝病(NAFLD)形成中氧化应激及细胞因子的动态变化及意义。方法 48只雄性长爪沙鼠随机分为正常组和模型组,每组24只,分别给予普通饲料和高脂饲料喂养,在实验第4周、第8周和第16周末每组分别处理8只沙鼠,化学法动态检测肝组织匀浆MDA含量以及SOD、GSH-PX和T-AOC活力,液相悬浮芯片技术动态检测血清TNF-α、INF-γ、IL-10等细胞因子水平。结果随NAFLD疾病的进展,沙鼠肝组织MDA含量逐渐增加,且均较正常组明显增高(P<0.01);T-AOC水平先略升高后降低,4周、16周时较正常组显著下降(P<0.05);SOD水平先显著增高后明显降低,4周时较正常组明显增高(P<0.05),8周、16周时明显降低(P<0.05、P<0.01);GSH-PX水平呈逐渐下降趋势,8周、16周时较正常组明显降低(P<0.05)。血清细胞因子TNF-α、IFN-γ随NAFLD进展逐渐增加,IL-10水平则逐渐降低,在8周、16周时与正常组有统计学差异(P<0.05、P<0.01)。结论高脂诱导的长爪沙鼠NAFLD模型氧化应激相关指标及炎症细胞因子随着单纯脂肪肝向脂肪性肝炎、肝纤维化及肝硬化的发展而出现显著变化,参与NAFLD的发生和发展。

Objective To explore the dynamic changes of oxidative stress and cytokines in Mongolian gerbils with nonalcoholic fatty liver disease（ NAFLD） and their significance. Methods Forty-eight healthy male gerbils were randomly divided into normal group and model group,24 in each group. Gerbils of the model group were fed with high fat diet while those of the normal group with normal diet. Eight gerbils in each group were killed at the end of 4 w,8 w and 16 w,respectively. MDA content and SOD,GSH-PX and T-AOC activity in the liver tissue were detected by chemical method,and serum TNF-α,INF-γ and IL-10 levels were determined using liquid suspension chip. Results With the development of NAFLD,MDA content in liver increased gradually,and the MDA contents were all significantly higher than those of the normal group（ P〈0. 01）; T-AOC level slightly increased,and then decreased,the levels at 4 w and 16 w were markedly decreased compared with those of the normal group（ P〈0. 05）; SOD level was significantly increased andthen markedly reduced,the level of the model group at 4 w was significantly increased（ P〈0. 05）,while that at 8 w and16 w were significantly decreased（ P〈0. 05,P〈0. 01）. The level of GSH-PX was decreased gradually,the levels at 8 w and 16 w were significantly lower than those of the normal group（ P〈0. 05）. With the progression of NAFLD,serum TNF-α and IFN-γ were increased gradually,while the level of IL-10 decreased gradually,and the levels at 8 w and 16 w were significantly lower than those of the normal group（ P〈0. 05,P〈0. 01）. Conclusions The oxidative stress-related indicators and inflammatory cytokines in the gerbil NAFLD models induced by high fat diet are significantly changed as simple fatty liver develops into steatohepatitis,liver fibrosis and cirrhosis,and participate in the development and progression of NAFLD.