[1]王 磊,王海强.3-磷酸肌醇依赖性蛋白激酶1基因敲除对心肌梗死诱导心力衰竭小鼠心血管重构的影响及其机制研究[J].陕西医学杂志,2022,51(5):547-551.[doi:DOI:10.3969/j.issn.1000-7377.2022.05.008]
　WANG Lei,WANG Haiqiang.Effect of PDK1 gene knockout on cardiovascular remodeling in mice with heart failure induced by myocardial infarction and its mechanism[J].,2022,51(5):547-551.[doi:DOI:10.3969/j.issn.1000-7377.2022.05.008]
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3-磷酸肌醇依赖性蛋白激酶1基因敲除对心肌梗死诱导心力衰竭小鼠心血管重构的影响及其机制研究
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
51
期数:
2022年5期
页码:
547-551
栏目:
基础研究
出版日期:
2022-05-05

文章信息/Info

Title:
Effect of PDK1 gene knockout on cardiovascular remodeling in mice with heart failure induced by myocardial infarction and its mechanism
作者:
王 磊1; 王海强2
(1.西安市中心医院心内科,陕西 西安 710004; 2.空军第九八六医院心血管内科,陕西 西安 710054)
Author(s):
WANG Lei; WANG Haiqiang
(Department of Cardiology,Xi'an Central Hospital,Xi'an 710004,China)
关键词:
3-磷酸肌醇依赖性蛋白激酶1;  心肌梗死;  心力衰竭;  心血管重构;  炎性因子;  血流动力学
Keywords:
3-phosphoinositide-dependent protein kinase 1;  Myocardial infarction;  Heart failure;  Cardiovascular remodeling;  Inflammation factor;  Hemodynamics
分类号:
R 541.4
DOI:
DOI:10.3969/j.issn.1000-7377.2022.05.008
文献标志码:
A
摘要:
目的:研究3-磷酸肌醇依赖性蛋白激酶1(PDK1)基因敲除对心肌梗死诱导的心力衰竭小鼠心血管重构的影响,并探讨其潜在的机制。方法:随机选取15只野生型雄性昆明小鼠作为对照组,20只野生型雄性昆明小鼠(模型组)和20只心肌组织PDK1敲除雄性昆明小鼠(PDK1组)通过结扎小鼠冠状动脉前降支制备心肌梗死诱导的心力衰竭模型。对照组小鼠仅开胸而不结扎动脉。术后1周,模型组存活15只,PDK1组存活15只,对照组存活15只。术后4周,观察并比较三组小鼠心电图(P波、QRS波宽度、S波),血流动力学指标[左心室收缩压(LVSP)、左室舒张末压(LVEDP)、左室最大压力下降速率(-dp/dtmax)和左室最大压力上升速率(+dp/dtmax)],心室重构指标(心重指数、心肌细胞横截面积),血清和心肌组织炎性因子含量[肿瘤坏死因子-α(TNF-α)、白细胞介素1β(IL-1β)、白细胞介素10(IL-10)]及脑钠肽(BNP)的含量。结果:术后4周,与对照组相比,模型组小鼠心电图S-T段升高明显,其中P波高度和QRS波宽度显著降低(均P<0.05),而P波宽度、S波宽度和高度均显著升高(均P<0.05); 与对照组比较,模型组和PDK1组血流动力学指标LVEDP显著升高(P<0.05),而LVSP、+dp/dtmax和-dp/dtmax均显著降低(均P<0.05); 与对照组小鼠相比,模型组和PDK1组小鼠心重指数、心肌细胞横截面积均显著升高(均P<0.05),并且PDK1组小鼠心重指数、心肌细胞横截面积均显著高于模型组小鼠(均P<0.05); 与对照组小鼠相比,模型组和PDK1组小鼠血清和心肌组织TNF-α、IL-1β和BNP均显著升高(均P<0.05),而IL-10含量却显著下降(P<0.05)。此外,PDK1组小鼠血清和心肌组织TNF-α、IL-1β和BNP含量均显著高于模型组小鼠,而IL-10含量却显著低于模型组小鼠(均P<0.05)。结论:PDK1基因敲除加重心肌梗死诱导的心力衰竭而小鼠心血管重构,其机制可能与PDK1基因敲除加重炎性反应有关。
Abstract:
Objective:To study the effect of 3-phosphoinositide-dependent protein kinase 1(PDK1)gene knockout on cardiovascular remodeling in mice with heart failure induced by myocardial infarction,and to explore its underlying mechanism.Methods: Fifteen wild-type male Kunming mice were randomly selected as the control group.Twenty wild-type male Kunming mice(model group)and 20 myocardial tissue PDK1 knockout male Kunming mice(PDK1 group)developed myocardial infarction-induced heart failure models by ligating the anterior descending coronary artery.Mice in control group had only thoracotomy without arterial ligation.One week after the operation,15 animals survived in model group,15 survived in PDK1 group and 15 survived in control group.Four weeks after operation,the electrocardiogram indexes(P wave,QRS wave width,S wave),hemodynamic indexes(LVSP,LVEDP,+dp/dtmax and -dp/dtmax),ventricular remodeling indexes(heart weight index,myocardial cell cross-sectional area),serum and myocardial inflammatory factors indexes(TNF-α,IL-1β,IL-10)and BNP levels were observed and compared among the three groups.Results:Four weeks after operation,compared with the control group,the ST segment of the ECG in the model group was significantly increased,and the height of P wave and the width of the QRS wave were significantly decreased,while the width and height of P wave,width and height of S wave were significantly decreased(all P<0.05); compared with the control group,LVEDP in the model group and PDK1 group was significantly increased(P<0.05),while LVSP,+dp/dtmax and -dp/dtmax were significantly decreased(all P<0.05).Compared with the control group,the cardiac weight index and cross-sectional area of cardiomyocytes in the model group and PDK1 group were significantly increased,and the cardiac weight index and cross-sectional area of cardiomyocytes in the PDK1 group were significantly higher than those in the model group(all P<0.05); compared with the control group,the serum and myocardial tissue TNF-α,IL-1β and BNP of the model group and PDK1 group were significantly increased,while IL-10 content decreased significantly(all P<0.05); in addition,the serum and myocardial tissue TNF-α,IL-1β and BNP of the PDK1 group were significantly higher than those of the model group,while the IL-10 content was significantly lower than that of the model group(all P<0.05).Conclusion:PDK1 gene knockout aggravates myocardial infarction-induced heart failure and cardiovascular remodeling in mice,and the mechanism may be related to the aggravation of inflammatory response by PDK1 gene knockout.

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备注/Memo

备注/Memo:
基金项目:陕西省分子心脏病学重点实验室开放项目(KLMC-2018-02)
更新日期/Last Update: 2022-05-05