摘要
目的观察锌指蛋白（ZEB）1在大鼠肝纤维化模型中的表达情况及探讨重组ZEBl蛋白干预对纤维化程度的影响。方法36只健康SD大鼠随机分为三组：对照组、模型组、ZEBl干预组。模型组与干预组均用二甲基亚硝胺（DMN）造模，每周前三天腹腔注射DMN，持续4周；之后干预组按4μg／kg剂量尾静脉注射重组ZEBl蛋白，隔天1次，而模型组继续腹腔注射DMN，各持续3周。对照组以等量等渗盐水代替DMN。实验结束后处死大鼠，留取肝组织经HE和Masson染色观察各组肝脏的病理学形态；用RT-PCR和Westernblot检测肝组织转化生长因子（TGF）D1和ZEBl的表达情况。计量资料采用单因素方差分析，两两比较采用LSD检验；计数资料采用Fisher确切概率法。结果病理学染色显示：模型组肝组织变性坏死，有明显纤维间隔形成，可见假小叶；ZEBl干预组与模型组相比，炎性坏死更加明显，纤维化程度加深，蓝色纤维条索更粗，两组肝纤维化程度的差异有统计学意义（x^2=21．626，P〈0．01）。RT-PCR和Westernblot结果显示：ZEBl和TGFD1在模型组中表达水平较正常组高，差异有统计学意义（P〈0．01）；模型组与干预组比较，ZEBl和TGFp1在干预组中表达水平更高，差异同样有统计学意义（P〈0．01）。结论ZEBl可能通过参与TGFD／Smad通路促进大鼠肝纤维化的发展。
Objeelive To determine the role of zinc finger protein 1 （ZEB1） in liver fibrosis and in regards to expression of the tumor growth factor-beta （TGFβ） signaling factor using a rat model system. Methods Sprague-Dawley rats were randomly divided into a normal （control） group, liver fibrosis （model） group and a liver fibrosis ＋ therapy （ZEB 1 intervention） group. The model group and the ZEB 1 intervention group were given intraperitoneal injections of dimethylnitrosamine （DMN） for the first 3 days of each week over a 7-week period; starting at week 5, the ZEB1 intervention group was started on a routine of every other day tail vein injections of recombinant ZEB 1. During this 7-week period, the control group was given intraperitoneal injections of 0.9% NaCI alone on the DMN schedule. Liver tissues were collected for pathological examination （with hematoxylin-eosin and Masson staining） and for detection of TGFβ1 and ZEB1 expression （by RT-PCR and western blotting）. Measurement data were compared between groups using the single-factor analysis of variance test, followed by the least significant difference LSD test. Count data were analyzed by Fisher＇s exact test. Results The model group＇s liver tissues showed degeneration and necrosis, as well as obvious fibrous septa accompanied by pseudo lobules. The ZEB1 intervention group＇s liver tissues showed a significantly higher degree of fibrosis （x2 = 21.63, P = 0）, with more coarse fiber cords.The expression of ZEB 1 and TGF[31 was significantly higher in the model group than in the control group （both P 〈 0.05）. However, the ZEB1 intervention group showed the highest levels of ZEB1 and TGFJ^I expression （vs. model group, P 〈 0.05）. Conclusion ZEB1 may promote the development of liver fibrosis in rats through a mechanism involving the TGFβ/Smad signaling pathway.
出处
《中华肝脏病杂志》
CAS
CSCD
北大核心
2014年第4期285-288,共4页
Chinese Journal of Hepatology
关键词
肝硬化
转化生长因子Β
锌指蛋白1
Liver cirrhosis
Transforming growth factor β
Zinc finger protein I
