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目的研究腺病毒介导的成年小鼠心肌直接蛋白激酶(PK)Cε基因转移对左心室收缩功能的影响。方法使用标准方法建立表达PKCε基因的重组腺病毒载体。直接注射重组腺病毒到FVB/N和ICR小鼠心肌,对照鼠给予相同剂量空载腺病毒。Western免疫印迹测定PKCε蛋白质表达水平。用非开胸经颈总动脉插管的显微外科技术评价小鼠左心室收缩功能。结果与对照鼠相比基因转移鼠心肌转基因PKCε蛋白质表达水平增加近4倍,基线左心室最大收缩压、最大收缩速率(dP/dt)、-dP/dt明显降低,左心室舒张末压、舒张压明显升高(P<0.01),异丙肾上腺素刺激后左心室dP/dt随剂量递增的依次升高明显抑制(P<0.01),PKCε基因转移鼠心脏质量/体质量比也较对照鼠明显增加(P<0.01)。结论腺病毒介导的、心肌直接的PKCε基因转移诱发了左心室收缩功能降低,导致了心肌肥厚和心力衰竭。
Objective To study the effect of adenovirus-mediated myocardial PKCε gene transfer on left ventricular systolic function in adult mice. Methods The recombinant adenovirus vector expressing the PKCε gene was established using standard methods. Direct injection of recombinant adenovirus into FVB / N and ICR mouse myocardium, control mice were given the same dose of empty vector. Western blot was used to determine PKCε protein expression. Evaluation of Left Ventricular Systolic Function in Mice by Non-thoracotomy with Common Carotid Artery by Microsurgical Technique. Results Compared with control mice, the expression of PKCε protein in gene transfer myocardium increased nearly 4-fold, and the maximal systolic pressure, dP / dt and dP / dt of left ventricle were significantly decreased in baseline LV diastolic and diastolic (P <0.01). The dP / dt of left ventricle increased markedly after the isoproterenol stimulation (P <0.01), and the heart mass / body mass ratio of PKCε gene transfer rats was also significantly higher than that of the control rats Significantly increased (P <0.01). Conclusions Adenovirus-mediated, direct myocardial PKCε gene transfer induces a decrease in left ventricular systolic function leading to cardiac hypertrophy and heart failure.