摘要
目的研究腺相关病毒为载体的心肌肌浆网钙离子ATP酶2a(SERCA2a)基因转导对慢性心力衰竭(CHF)大鼠的短期治疗作用。方法将大鼠分为4个组:对照组,CHF组,CHF+eGFP组和CHF+SERCA2a组。采用腹主动脉缩窄术建立慢性心力衰竭大鼠模型,应用经腹心包腔内注射术分别将生理盐水、携带eGFP基因的重组腺相关病毒和携带SERCA2a基因的重组腺相关病毒导入CHF组、CHF+eGFP组和CHF+SERCA2a组大鼠心脏。于导入后10天检测各组大鼠的心脏收缩和舒张功能、SERCA2a蛋白表达水平和活性。结果慢性心力衰竭大鼠心脏内转导入SERCA2a基因10天后,CHF+eGFP组SERCA2a蛋白表达水平和活性较CHF组大鼠明显增加(SERCA2a蛋白表达增加80.7%,活性增加89.9%),但低于对照组大鼠蛋白表达水平(约为对照组的67.6%)和活性水平(约为对照组的77.7%);大鼠的心脏功能随着SERCA2a功能的增强而改善,左室收缩压峰值和左室内压最大下降速率已达到对照组水平,左室舒张末压力和左室内压最大上升速率虽未达到对照组水平,但较CHF组明显改善。结论CHF大鼠心脏SERCA2a蛋白表达水平及活性较对照大鼠明显下降;SERCA2a基因转导对慢性心力衰竭具有良好的短期治疗作用。
Objective To study the short-term therapeutic effects of adeno-associated viral gene transfer of sarcoplasmic reticulum Ca^2＋ATPase （SRCA2a） on chronic heart failure （CHF）. Methods The rats were divided into four groups： control group, CHF group, CHF＋eGFP group and CHF＋SRCA2a group. CHF rats were obtained by creating descending aortic constriction. 0. 9% sodium chloride solution, recombinant adeno-associated virus carrying enhanced green fluorescent protein （eGFP） gene, and recombinant adeno-associated virus carrying SRCA2a gene, were respectively injected into pericardium of heart failure rats in different groups by intraperieardial injection via tmns-diaphragmatic approach. 10 days after gene transfer, hemodynamic parameters, the protein expression of SRCA2a and the SRCA2a activity were measured and analyzed respectively. Results 10 days after gene transfer, the protein expression and activity of SRCA2a were increased by 80. 7% and 89.9% respectively, but still lower than those in the control rats. The heart function was also improved along with the increase of SRCA2a expression and activity. The left ventricular systolic pressure and the maximal rate of decline of left ventricular pressure in CHF＋SRCA2a group were similar with those of the controls. The left ventricular end-diastolic pressure and the maximal rate of rise of left-ventricular pressure were much improved, but did not reach the level of the controls. Conclusions SRCA2a protein levels and activity are significantly decreased in CHF rats. Adeno-associated viral gene transfer of SRCA2a can improve the function of the heart in short term.
出处
《解放军医学杂志》
CAS
CSCD
北大核心
2007年第5期485-488,共4页
Medical Journal of Chinese People's Liberation Army
基金
国家自然科学基金资助项目(30470716)
国家重点基础研究发展规划项目(G2000056906)
