Gou Zhongshan, Yan Xinxin, Jia Hongjing, Sun Kangyun, Li Ping, Zhang Qian, Deng Xuedong
Center for Medical Ultrasound, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215000, P.R. China.
Department of Pharmacy, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu 215000, P.R. China.
Exp Ther Med. 2020 Dec;20(6):132. doi: 10.3892/etm.2020.9261. Epub 2020 Oct 2.
Sarco/endoplasmic reticulum Ca²-ATPase (SERCA2a) is important for cardiac physiological function and pathological progression. However, intravenous injection, a commonly applied approach for gene delivery in most studies investigating the expression of SERCA2a in cardiomyocytes, has not been particularly satisfactory. Therefore, in the present study, a modified method was used to transfect this gene into the heart. Specifically, a SERCA2a-knockdown lentivirus was directly injected into the myocardium of adult rats under ultrasound guidance, following which the effectiveness and feasibility of this proposed approach were evaluated. The results demonstrated that compared with traditional intravenous injection, the modified gene delivery method resulted in markedly higher transfection efficiency. In addition, the SERCA2a-knockdown rats exhibited higher rates of arrhythmia and weaker ventricular wall motions compared with those in the control rats, with these symptoms more evident in the rats that received a direct injection into the myocardium compared with those that were intravenously injected. These results suggest that ultrasound-guided injection into the myocardium is an efficient and safe method for gene delivery and for inducing the knockdown of SERCA2a protein expression in cardiomyocytes in their native environment.
肌浆网/内质网Ca²⁺-ATP酶（SERCA2a）对心脏生理功能和病理进展至关重要。然而，在大多数研究心肌细胞中SERCA2a表达的实验中，常用的基因递送方法——静脉注射，效果并不特别理想。因此，在本研究中，采用了一种改良方法将该基因转染至心脏。具体而言，在超声引导下，将SERCA2a基因敲低慢病毒直接注射到成年大鼠心肌中，随后评估该方法的有效性和可行性。结果表明，与传统静脉注射相比，改良后的基因递送方法转染效率显著更高。此外，与对照大鼠相比，SERCA2a基因敲低大鼠的心律失常发生率更高，室壁运动更弱，与静脉注射的大鼠相比，直接注射到心肌的大鼠这些症状更明显。这些结果表明，超声引导下心肌内注射是一种高效、安全的基因递送方法，可在心肌细胞的自然环境中诱导SERCA2a蛋白表达的敲低。
