摘要
目的探讨肝特异性敲除Yes相关蛋白(YAP)基因对CCl4诱发的肝纤维化的改善作用机制。方法按照体重将肝特异性敲除YAP基因小鼠随机分为4组:正常-1组、模型-1组、正常-2组和模型-2组,每组10只。模型组小鼠腹腔注射20%四氯化碳制备肝纤维化模型;正常组小鼠注射等量生理盐水。6周后取材。用试剂盒法检测小鼠肝匀浆中超氧化物歧化酶(SOD)和丙二醛(MDA)含量,用逆转录-聚合酶链和蛋白质印迹法分别检测小鼠肝中YAP以及纤维化因子的基因或蛋白表达水平。结果正常-1组、模型-1组、正常-2组和模型-2组的SOD含量分别为(13.01±3.35),(7.36±1.76),(20.67±2.37)和(17.80±2.17)U·mg^(-1);MDA含量分别为(0.04±0.01),(0.10±0.01),(0.07±0.02)和(0.04±0.01)U·mg^(-1);Collagen fiber1蛋白相对表达分别为1.24±0.52,3.41±0.56,1.19±0.42和1.17±0.52;α-SMA蛋白的相对表达分别为1.30±0.55,3.99±0.49,0.75±0.05和1.12±0.53。模型-1组与正常-1组相比,小鼠肝SOD的蛋白含量明显下降,而MDA、Collagen fiber1和α-SMA的蛋白含量明显增加;模型-2组与模型-1组比较,小鼠肝中SOD的蛋白含量明显上升,而MDA、Collagen fiber1和α-SMA的蛋白表达明显减少。组间比较,上述指标的差异均有统计学意义(P<0.05,P<0.01)。结论肝特异性敲除YAP基因可通过抗氧化作用改善CCl4诱发的肝纤维化。
Objective To investigate whether liver-specific Yesassociated protein (YAP) knockout can improve liver fibrosis induced by CCl4in mice,and evaluate its antioxidant mechanism.Methods Both According to their body weight,the liver-specific YAP gene knockout mice were randomly divided into 4 groups were set as:normal-1 group,model-1 group,normal-2 group and model-2 group.There was 10mice in each group.Mice in the model group were injected intraperitoneally with 20%carbon tetrachloride to prepare liver fibrosis models;mice in the normal group were injected with the same amount of normal saline.After 6 weeks,get the material.The contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in mouse liver homogenate were detected by kit.The gene or protein expression levels of YAP and fibrosis factor in mouse liver were detected by reverse transcription-PCR and Western blotting respectively.Results The SOD content of normal-1 group,model-1 group,normal-2 group and model-2 group were (13.01±3.35),(7.36±1.76),(20.67±2.37) and (17.80±2.17) U·mg^(-1);the MDA content were (0.04±0.01),(0.10±0.01),(0.07±0.02) and (0.04±0.01) U·mg^(-1);the relative expression of Collagen fiber1 protein were1.24±0.52,3.41±0.56,1.19±0.42,1.17±0.52;the relative expression ofα-SMA protein were 1.30±0.55,3.99±0.49,0.75±0.05,1.12±0.53.Compared with the normal-1 group,the protein content of liver SOD in the model-1 group decreased significantly;the protein content of MDA,Collagen fiber1 andα-SMA increased significantly.In addition,compared with the model-1 group,the protein content of SOD in the liver of the model-2group increased significantly,while the protein expression of MDA,Collagen fiber1 andα-SMA decreased significantly.Comparison between the two groups,the difference of the factors were significant(P<0.05,P<0.01).Conclusion Liver-specific knockout of YAP gene can improve liver fibrosis induced by CCl4through antioxidant effects.
作者
陈雅静
郝鹏
代玉娇
宋宏宇
李一达
高明明
李爽
薛丽会
齐亚娟
CHEN Ya-jing;HAO Peng;DAI Yu-jiao;SONG Hong-yu;LI Yi-da;GAO Ming-ming;LI Shuang;XUE Li-hui;QI Ya-juan(College of Pharmacy,Key Laboratory of Chronic Diseases of Hebei Province and Key laboratory of Basic Clinical Research of Chronic Diseases of Tangshan City,North China University of Science and Technology Hebei,Tangshan 063000,Hebei Province,China;Basic Medical College,Key Laboratory of Chronic Diseases of Hebei Province and Key laboratory of Basic Clinical Research of Chronic Diseases of Tangshan City,North China University of Science and Technology Hebei,Tangshan 063000,Hebei Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2021年第17期2316-2319,共4页
The Chinese Journal of Clinical Pharmacology
基金
国家自然科学基金资助项目(81471022)
河北省自然科学基金资助项目(H2018209341)。
关键词
肝纤维化
Yes相关蛋白
超氧化物歧化酶
丙二醛
四氯化碳
liver fibrosis
Yes-associated protein
superoxide dismutase
malonaldehyde
carbon tetrachloride
