首页|2-甲氧基雌二醇对布-加综合征模型小鼠肝纤维化的影响

2-甲氧基雌二醇对布-加综合征模型小鼠肝纤维化的影响

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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(Col Ⅰ)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-1α mRNA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.
Effects of 2-methoxyestradiol on hepatic fibrosis in Budd-Chiari syndrome model mice
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 detec-ted;pathological changes of liver were observed by HE staining,collagen deposition was observed by sirius red staining,the expression of α-smooth muscle actin(α-SMA)was observed by immunohistochemical staining,and the mRNA and protein expressions of fibronectin(FN),type Ⅰcollagen(ColⅠ)and hypoxia inducible factor-1α(HIF-1α)were measured by re-al-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,Col Ⅰ,HIF-1α mRNA expression,FN,ColⅠ,HIF-1α protein expression levels increased(P<0.05).After 2-MeOE2 intervention,the above indexes were de-creased(P<0.05).Conclusion:2-MeOE2 can improve hepatic fibrosis induced by BCS in mice,which may be related to improving hepatocyte hypoxia.

Budd-Chiari syndromehepatic fibrosis2-methoxyestradiolhypoxiamouse

徐大千、李素新、杨净、冯敏、党晓卫

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郑州大学第一附属医院重症医学科 郑州 450052

郑州大学第一附属医院肝胆胰外科 郑州 450052

布-加综合征 肝纤维化 2-甲氧基雌二醇 缺氧 小鼠

河南省医学科技攻关计划项目

SB201901003

2024

郑州大学学报(医学版)
郑州大学

郑州大学学报(医学版)

CSTPCD北大核心
影响因子:1.246
ISSN:1671-6825
年,卷(期):2024.59(5)