Cholinergic stimulation with pyridostigmine modulates a heart-spleen axis after acute myocardial infarction in spontaneous hypertensive rats.
Cholinergic stimulation with pyridostigmine modulates a heart-spleen axis after acute myocardial infarction in spontaneous hypertensive rats.
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DOI：
10.1038/s41598-021-89104-8
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发表时间：
2021-05-05
影响因子：
4.6
通讯作者：
Consolim-Colombo FM
中科院分区：
文献类型：
--
作者：
Bandoni RL;Bricher Choque PN;Dellê H;de Moraes TL;Porter MHM;da Silva BD;Neves GA;Irigoyen MC;De Angelis K;Pavlov VA;Ulloa L;Consolim-Colombo FM
在急性心肌梗死（AMI）后愈合过程中调节免疫细胞募集到心脏的机制具有重要的临床意义。我们研究了胆碱酯酶抑制剂吡啶斯的明的胆碱能刺激是否能调节自发性高血压大鼠（SHR）AMI后的心脏和脾脏免疫反应以及心脏重塑。成年雄性SHR接受假手术或左冠状动脉结扎，并随机分配至未治疗组或吡斯的明治疗组（40 mg/kg，每天一次，灌胃）。在MI后第6天测定血压和心率变异性，并进行超声心动图检查。心肌梗死后第7天，对心脏和脾脏进行免疫组织化学细胞分析（CD 3+和CD 4+淋巴细胞，以及CD 68+和CD 206+巨噬细胞），并测定TNF水平。吡斯的明治疗增加了心肌中的副交感神经张力和T CD 4+淋巴细胞，但降低了M1/M2巨噬细胞比率，其抗炎作用与心脏和脾脏中TNF水平降低有关。用这种胆碱能药物治疗改善了心脏重塑，表现为心室直径减小和功能参数改善。总之，吡啶斯的明的胆碱能刺激增强了副交感神经张力，诱导了心脏和脾脏的抗炎反应，促进了SHR AMI后心脏的恢复。
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.
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影响因子：
3.7
作者：
Durand MT;Becari C;de Oliveira M;do Carmo JM;Silva CA;Prado CM;Fazan R Jr;Salgado HC
通讯作者：
Salgado HC
影响因子：
3
作者：
Calvillo, Laura;Vanoli, Emilio;Schwartz, Peter J.
通讯作者：
Schwartz, Peter J.
影响因子：
5.7
作者：
Androne, AS;Hryniewicz, K;Katz, SD
通讯作者：
Katz, SD
影响因子：
2.7
作者：
Bratton, B. O.;Martelli, D.;McAllen, R. M.
通讯作者：
McAllen, R. M.
影响因子：
15.1
作者：
BELLINGER, DL;LORTON, D;FELTEN, DL
通讯作者：
FELTEN, DL