Department of Cardiovascular Surgery, Xijing Hospital, Air Force Medical University, Xi'an, China.
Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University School of Basic Medical Sciences, Xi'an Jiaotong University, Ministry of Education, Xi'an, China.
J Cardiovasc Pharmacol. 2019 Oct;74(4):336-347. doi: 10.1097/FJC.0000000000000711.
Melatonin, the receptors for which are abundant in the hypothalamic paraventricular nucleus (PVN), can protect the heart from myocardial ischemia-reperfusion (MI/R) injury. The aim of this study was to determine whether the infusion of melatonin into the PVN protects the heart from MI/R injury by suppressing oxidative stress or regulating the balance between proinflammatory cytokines and anti-inflammatory cytokines in MI/R rats. Male Sprague-Dawley rats were treated with a bilateral PVN infusion of melatonin. MI/R operation was performed 1 week after infusion. At the end of the third week after the infusion, all the rats were euthanized. This was followed by immunohistochemistry and immunofluorescence studies of the rats. MI/R rats showed larger infarct size, increased left ventricular (LV) end-diastolic volume, and decreased LV ejection fraction and LV fractional shortening. Moreover, MI/R rats had a higher level of norepinephrine in the plasma, heart, and PVN; higher PVN levels of reactive oxygen species, NOX2, NOX4, IL-1β, and NF-κB activity; and lower PVN levels of copper/zinc superoxide dismutase (Cu/Zn-SOD) and IL-10 compared with the sham group. Melatonin infusion in PVN reduced LV end-diastolic volume, norepinephrine, reactive oxygen species, NOX2, NOX4, IL-1β, and NF-κB activity, and increased LV ejection fraction, LV fractional shortening, Cu/Zn-SOD, and IL-10. Overall, these results suggest that the infusion of melatonin ameliorates sympathetic nerve activity and MI/R injury by attenuating oxidative stress and inflammatory cytokines in the PVN of MI/R rats.
褪黑素在丘脑室旁核（PVN）中大量存在其受体，能保护心脏免受心肌缺血再灌注（MI/R）损伤。本研究旨在确定 PVN 中褪黑素的输注是否通过抑制氧化应激或调节 MI/R 大鼠促炎细胞因子和抗炎细胞因子之间的平衡来保护心脏免受 MI/R 损伤。雄性 Sprague-Dawley 大鼠接受双侧 PVN 褪黑素输注。输注后 1 周进行 MI/R 手术。输注后第 3 周结束时，所有大鼠均安乐死。随后对大鼠进行免疫组织化学和免疫荧光研究。MI/R 大鼠的梗死面积较大，左心室（LV）舒张末期容积增加，LV 射血分数和 LV 缩短分数降低。此外，MI/R 大鼠的血浆、心脏和 PVN 中去甲肾上腺素水平升高；PVN 中活性氧、NOX2、NOX4、IL-1β和 NF-κB 活性升高；PVN 中铜/锌超氧化物歧化酶（Cu/Zn-SOD）和 IL-10 水平降低。PVN 中褪黑素输注可降低 LV 舒张末期容积、去甲肾上腺素、活性氧、NOX2、NOX4、IL-1β和 NF-κB 活性，并增加 LV 射血分数、LV 缩短分数、Cu/Zn-SOD 和 IL-10。总体而言，这些结果表明，褪黑素输注通过减轻 MI/R 大鼠 PVN 中的氧化应激和炎症细胞因子来改善交感神经活性和 MI/R 损伤。
