摘要
[目的]研究沙鼠非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)进展过程中Notch3/Hes1表达的动态变化,探讨其在脂肪性肝纤维化形成中的作用。[方法]长爪沙鼠48只,随机分为正常组和模型组,每组24只,正常组以普通饲料喂养,模型组以高脂饲料喂养,两组分别于实验第4、8、16周末各处理沙鼠8只,HE和Masson染色光镜观察肝组织病理,组织芯片免疫组化法检测肝组织Notch3、Hes1、α-SMA表达。[结果]和正常组比较,随着高脂饮食时间增加,模型组沙鼠肝组织逐渐出现脂肪变、炎症、纤维化甚至是肝硬化;正常组沙鼠肝组织仅少量Notch3、Hes1、α-SMA表达,模型组沙鼠肝组织Notch3、Hes1、α-SMA表达与同期正常组相比表达水平明显增加(P<0.05、P<0.01),第8周、16周时较第4周模型组增加明显(P<0.05、P<0.01);Notch3、Hes1蛋白表达水平与α-SMA蛋白表达呈现明显正相关(r=0.873和0.786,P<0.01)。[结论]Notch/Hes信号在沙鼠非酒精性脂肪性纤维化形成中活性增强,可能参与高脂诱导的非酒精性脂肪性肝纤维化的形成。
[Objective] To investigate the dynamic changes of Notch3/Hes1 signaling pathway in Mongolian gerbils with nonalcoholic fatty liver disease and explore their effect in the formation of liver fibrosis.[Methods] Forty-eight male gerbils were randomly divided into normal group and model group in average.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 of4 w, 8w and 16 w, respectively. The pathological changes of the liver tissue were observed by HE and Masson staining, and the expression of Notch3,Hes1 andα-SMA in liver was detected by tissue microarray immunohistochemistry. [Results]Compared with the normal group,the gerbils fed with high fat diet developed steatosis, inflammation, fibrosis and even cirrhosis gradually. Notch3,Hes1 and α-SMA in normal group only few expressed, while compared with the corresponding period of normal group their expression in model group increased significantly（P〈0.05, P〈0.01）. The levels at 8w and 16 w were markedly increased compared with those of at 4w（P〈0.05, P〈0.01）.The expression levels of Notch3 and Hes1 were positively correlated with the expression of α-SMA protein（R=0.786 and=0.873, respectively,P〈0.01）. [Conclusions]The activity of Notch/Hes signaling pathway enhances in the development of nonalcoholic fatty liver fibrosis in gerbils, suggesting that it may take part in the formation of nonalcoholic fatty liver fibrosis induced by high fat diet.
出处
《浙江中医药大学学报》
CAS
2017年第3期175-178,共4页
Journal of Zhejiang Chinese Medical University
基金
浙江省公益性技术应用研究计划项目(2012C37088)~~
关键词
NAFLD
肝星状细胞
纤维化
NOTCH信号通路
组织芯片
nonalcoholic fatty liver
hepatic stellate cell
fibrosis
Notch signaling pathway
tissue microarray
