野生型p53诱导的磷酸酶1基因缺失对小鼠心功能的影响

发布时间：2018-04-05 09:25

本文选题：小鼠　切入点：基因敲除　出处：《中国循环杂志》2017年08期

【摘要】：目的:探讨敲除野生型p53诱导的磷酸酶1(Wip1)基因对小鼠心功能的影响及心脏组织中基因和蛋白表达水平的变化。方法:随机选取野生型(WT)小鼠和Wip1基因敲除(Wip1-KO)小鼠各10只,分别检测两组小鼠的心功能和心重/体重比,应用苏木精伊红(HE)染色观察小鼠心肌组织的病理形态,应用实时定量反转录聚合酶链式反应(RT-PCR)检测心肌组织中心房利钠肽(ANP)、B型利钠肽(BNP)、单核细胞趋化蛋白-1(MCP-1)和α-平滑肌肌动蛋白(α-SMA)的基因表达水平,并应用蛋白免疫印迹(Western blot)检测凋亡相关蛋白包括B淋巴细胞瘤-2(Bcl-2)、B淋巴细胞瘤-2相关X蛋白(Bax)和活化半胱氨酸天冬氨酸蛋白酶-3(c-Caspase3)的表达水平。结果:与WT组小鼠相比,Wip1-KO组小鼠心肌组织中Wip1 mRNA表达明显降低(P0.05),左心室射血分数和左心室缩短分数降低(P0.05),左心室收缩末期内径增大(P0.05)。虽然Wip1-KO组小鼠与WT小鼠的心脏重量没有差异,但Wip1-KO组小鼠体重较WT组小鼠减轻(P0.05),心重/体重比增加(P0.05)。HE染色显示Wip1-KO组小鼠的心肌形态与WT组小鼠之间没有明显差异。心肌组织中ANP、BNP、MCP-1和α-SMA基因表达水平在两组小鼠之间差异无统计学意义(P0.05)。Wip1-KO组小鼠心肌组织中凋亡相关蛋白Bax/Bcl-2和c-Caspase3表达水平与WT组小鼠之间没有明显差异(P0.05)。结论:敲除Wip1基因可以损害小鼠心功能,但相关的机制还有待进一步阐明。
[Abstract]:Aim: to investigate the effects of knockout p53 induced phosphatase 1 (Wip1) gene on cardiac function and the changes of gene and protein expression in heart tissue of mice.Methods: the cardiac function and heart weight / body weight ratio were measured in 10 wild type WTW mice and 10 Wip1 knockout Wip1-KOO mice. The pathological morphology of myocardial tissue was observed by hematoxylin eosin (HEH) staining.Real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to detect the gene expression levels of atrial natriuretic peptide (ANPP) B type natriuretic peptide (BNPP), monocyte chemotactic protein (MCP-1) and 伪 -SMA-1 in cardiac tissue.The expression of apoptosis-related proteins, including B lymphocytoma Bcl-2 associated X protein Baxand activated cysteine aspartate protease -3c-Caspase3, was detected by Western blot.Results: compared with WT group, the expression of Wip1 mRNA in myocardium of Wip1-KO group decreased significantly (P 0.05), left ventricular ejection fraction (LVEF) and left ventricular shortening fraction decreased (P 0.05), and left ventricular end-systolic diameter increased (P 0.05).Although there was no difference in heart weight between Wip1-KO group and WT mice, the weight of mice in Wip1-KO group was lower than that in WT group, and the increase of heart weight / body weight ratio showed that there was no significant difference in myocardial morphology between Wip1-KO group and WT group.Conclusion: knockout of Wip1 gene can damage cardiac function in mice, but the related mechanism needs to be further elucidated.
【作者单位】：北京协和医学院中国医学科学院国家心血管病中心阜外医院;中国医学科学院医学实验动物研究所北京协和医学院比较医学中心;中国医学科学院基础医学研究所北京协和医学院基础学院;
【基金】：国家自然科学基金(81270288,81541095)
【分类号】：R54

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