2-甲氧基雌二醇对布-加综合征模型小鼠肝纤维化的影响  

Effects of 2-methoxyestradiol on hepatic fibrosis in Budd-Chiari syndrome model mice

作　　者：徐大千[1] 李素新[2] 杨净 冯敏[1] 党晓卫[2] XU Daqian;LI Suxin;YANG Jing;FENG Min;DANG Xiaowei(Department of Critical Care Medicine,the First Affiliated Hospital,Zhengzhou University,Zhengzhou 450052;Department of Hepatopancreatobiliary Surgery,the First Affiliated Hospital,Zhengzhou University,Zhengzhou 450052)

机构地区：[1]郑州大学第一附属医院重症医学科,郑州450052 [2]郑州大学第一附属医院肝胆胰外科,郑州450052

出　　处：《郑州大学学报（医学版）》2024年第5期617-620,共4页Journal of Zhengzhou University(Medical Sciences)

基　　金：河南省医学科技攻关计划项目(SB201901003)。

摘　　要：目的:探讨2-甲氧基雌二醇(2-MeOE2)对布-加综合征(BCS)所致肝纤维化的影响和可能机制。方法:40只C57BL/6J雄性小鼠随机分为4组,每组10只,BCS组、BCS+2-MeOE2组采用下腔静脉部分结扎法制备BCS模型,假手术组和2-MeOE2组行造模操作但不结扎;2-MeOE2组和BCS+2-MeOE2组每隔1日腹腔注射2-MeOE2(15 mg/kg)1次。6周后处死小鼠,取血清检测ALT与AST水平;取肝组织,HE染色观察病理改变,天狼星红染色观察胶原沉积情况,免疫组化染色观察α-平滑肌肌动蛋白(α-SMA)的表达,实时荧光定量PCR法检测肝组织中纤维连接蛋白(FN)、Ⅰ型胶原(ColⅠ)和缺氧诱导因子-1α(HIF-1α)mRNA的表达,Western blot法检测上述蛋白的表达。结果:与假手术组相比,BCS组小鼠肝脏淤血,胶原沉积,ALT、AST水平升高,α-SMA表达水平升高,FN、ColⅠ、HIF-1αmRNA和蛋白表达水平升高(P<0.05);2-MeOE2可拮抗BCS导致的上述指标的变化(P<0.05)。结论:2-MeOE2可以改善BCS所致的小鼠肝纤维化,作用机制可能与改善肝细胞缺氧有关。Aim:To investigate the effects of 2-methoxyestradiol(2-MeOE2)on hepatic fibrosis caused by Budd-Chiari syndrome(BCS)and its possible mechanism.Methods:A total of 40 C57BL/6J male mice were randomly allocated into 4 groups with 10 in each group.Partial ligation of inferior vena cava was performed in BSC group and BCS+2-MeOE2 group,and sham operation group and 2-MeOE2 group were not ligated;for mice in 2-MeOE2 group and BCS+2-MeOE2 group,2-MeOE2(15 mg/kg)was injected intraperitoneally 1 time every other day.After 6 weeks,serum ALT and AST were detected;pathological changes of liver were observed by HE staining,collagen deposition was observed by sirius red staining,the expression ofα-smooth muscle actin(α-SMA)was observed by immunohistochemical staining,and the mRNA and protein expressions of fibronectin(FN),typeⅠcollagen(ColⅠ)and hypoxia inducible factor-1α(HIF-1α)were measured by real-time fluorescence quantitative PCR and Western blot,respectively.Results:Compared with the sham operation group,BCS group had liver congestion,collagen deposition,ALT,AST,α-SMA expression,FN,ColⅠ,HIF-1αmRNA expression,FN,ColⅠ,HIF-1αprotein expression levels increased(P<0.05).After 2-MeOE2 intervention,the above indexes were decreased(P<0.05).Conclusion:2-MeOE2 can improve hepatic fibrosis induced by BCS in mice,which may be related to improving hepatocyte hypoxia.

关 键 词：布-加综合征 肝纤维化 2-甲氧基雌二醇 缺氧 小鼠 

分 类 号：R656[医药卫生—外科学]