Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, Sichuan, China.
Shanxi University of Traditional Chinese Medicine, Jinzhong, 030002, Shanxi, China.
J Cardiovasc Transl Res. 2022 Oct;15(5):1176-1191. doi: 10.1007/s12265-022-10245-w. Epub 2022 Apr 4.
Angina pectoris is the most common manifestation of coronary heart disease, causing suffering in patients. Electroacupuncture at PC6 can effectively alleviate angina by regulating the expression of genes, whether the alternative splicing (AS) of genes is affected by acupuncture is still unknown. We established a rat model of myocardial ischemia-reperfusion by coronary artery ligation and confirmed electroacupuncture alleviated the abnormal discharge caused by angina pectoris measured in EMG electromyograms. Analysis of the GSE61840 dataset established that AS events were altered after I/R and regulated by electroacupuncture. I/R decreased the expression of splicing factor Nova1 while electroacupuncture rescued it. Further experiments in dorsal root ganglion cells showed Nova1 regulated the AS of the GABRG2, specifically on its exon 9 where an important phosphorylation site is present. In vivo, results also showed that electroacupuncture can restore AS of GABRG2. Our results proved that electroacupuncture alleviates angina results by regulating alternative splicing.
心绞痛是冠心病最常见的表现形式，给患者带来痛苦。PC6 电针对心绞痛有明显的治疗作用，其机制可能与基因表达调控有关，但针刺是否影响基因的可变剪接仍不清楚。本研究通过结扎大鼠冠状动脉建立心肌缺血再灌注模型，电针可减轻 EMG 肌电图检测到的由心绞痛引起的异常放电，证实电针对心绞痛具有治疗作用。通过对 GSE61840 数据集的分析发现，电针可以调节缺血再灌注引起的可变剪接事件。缺血再灌注降低了剪接因子 Nova1 的表达，而电针则挽救了这一作用。进一步在背根神经节细胞中的实验表明，Nova1 调节 GABRG2 的可变剪接，特别是其含有重要磷酸化位点的外显子 9。体内实验也表明电针可以恢复 GABRG2 的可变剪接。本研究结果证实电针通过调节可变剪接缓解心绞痛。
