Biotechnology Laboratory, Postgraduate Program in Medicine, Universidade Nove de Julho (UNINOVE), São Paulo, SP, Brazil.
Hypertension Unit, Heart Institute (INCOR), Medical School of University of São Paulo, São Paulo, SP, Brazil.
Sci Rep. 2021 May 5;11(1):9563. doi: 10.1038/s41598-021-89104-8.
The mechanisms regulating immune cells recruitment into the heart during healing after an acute myocardial infarction (AMI) have major clinical implications. We investigated whether cholinergic stimulation with pyridostigmine, a cholinesterase inhibitor, modulates heart and spleen immune responses and cardiac remodeling after AMI in spontaneous hypertensive rats (SHRs). Male adult SHRs underwent sham surgery or ligation of the left coronary artery and were randomly allocated to remain untreated or to pyridostigmine treatment (40 mg/kg once a day by gavage). Blood pressure and heart rate variability were determined, and echocardiography was performed at day six after MI. The heart and spleen were processed for immunohistochemistry cellular analyses (CD3 and CD4 lymphocytes, and CD68 and CD206 macrophages), and TNF levels were determined at day seven after MI. Pyridostigmine treatment increased the parasympathetic tone and T CD4 lymphocytes in the myocardium, but lowered M1/M2 macrophage ratio towards an anti-inflammatory profile that was associated with decreased TNF levels in the heart and spleen. Treatment with this cholinergic agent improved heart remodeling manifested by lower ventricular diameters and better functional parameters. In summary, cholinergic stimulation by pyridostigmine enhances the parasympathetic tone and induces anti-inflammatory responses in the heart and spleen fostering cardiac recovery after AMI in SHRs.
调节急性心肌梗死(AMI)后愈合过程中心脏免疫细胞募集的机制具有重要的临床意义。我们研究了在自发性高血压大鼠(SHR)中,用乙酰胆碱酯酶抑制剂吡啶斯的明进行胆碱能刺激是否能调节心脏和脾脏的免疫反应以及 AMI 后的心脏重构。雄性成年 SHR 接受假手术或左冠状动脉结扎,并随机分为未治疗组或吡啶斯的明治疗组(每天 1 次,通过灌胃给予 40mg/kg)。在 MI 后 6 天测定血压和心率变异性,并进行超声心动图检查。在 MI 后 7 天对心脏和脾脏进行免疫组织化学细胞分析(CD3 和 CD4 淋巴细胞,CD68 和 CD206 巨噬细胞),并测定 TNF 水平。吡啶斯的明治疗增加了心肌中的副交感神经张力和 T CD4 淋巴细胞,但降低了 M1/M2 巨噬细胞比值,向抗炎表型转变,这与心脏和脾脏中 TNF 水平降低有关。这种胆碱能药物的治疗改善了心室直径和更好的功能参数,表明心脏重构得到改善。总之,吡啶斯的明的胆碱能刺激增强了副交感神经张力,并在 SHR 的 AMI 后诱导心脏和脾脏中的抗炎反应,促进心脏恢复。