Department of Cardiovascular Surgery, Xijing Hospital, Air Force Medical University, Xi'an, China.
Department of Cardiac Surgery, Xi'an International Medical Center Hospital, Xi'an, China; and.
J Cardiovasc Pharmacol. 2020 Aug;76(2):197-206. doi: 10.1097/FJC.0000000000000851.
Previous studies have shown that melatonin (Mel) can effectively ameliorate myocardial ischemia/reperfusion (MI/R) injury, but the mechanism is yet to be fully elucidated. Mel receptors are expressed in the paraventricular nucleus (PVN), which is also involved in regulating cardiac sympathetic nerve activity. The aim of this study was to examine whether Mel receptors in the PVN are involved in the protective effects of Mel against MI/R injury. The results of quantitative polymerase chain reaction, western blot, and immunofluorescence assays indicated that Mel receptor 2 (MT2) expression in the PVN was upregulated after MI/R. Intraperitoneal administration of Mel significantly improved post-MI/R cardiac function and reduced the infarct size, whereas shRNA silencing of MT2 in the PVN partially blocked this effect. Intraperitoneal administration of Mel reduced sympathetic nerve overexcitation caused by MI/R, whereas shRNA silencing of MT2 in the PVN partially diminished this effect. Furthermore, enzyme-linked immunosorbent assay and western blot results indicated that intraperitoneal administration of Mel lowered the levels of inflammatory cytokines in the PVN after MI/R injury, whereas the application of sh-MT2 in the PVN reduced this effect of Mel. Mel significantly reduced the levels of NF-κB after astrocyte oxygen and glucose deprivation/reoxygenation injury, and this effect was offset when MT2 was silenced. The above experimental results suggest that MT2 in the PVN partially mediated the protective effects of Mel against MI/R injury, and its underlying mechanisms may be related to postactivation amelioration of PVN inflammation and reduction of cardiac sympathetic nerve overexcitation.
先前的研究表明，褪黑素（Mel）可有效改善心肌缺血/再灌注（MI/R）损伤，但作用机制尚不完全清楚。褪黑素受体在室旁核（PVN）表达，该核也参与调节心脏交感神经活动。本研究旨在探讨 PVN 中的 Mel 受体是否参与了 Mel 对 MI/R 损伤的保护作用。定量聚合酶链反应、western blot 和免疫荧光检测结果表明，MI/R 后 PVN 中的 Mel 受体 2（MT2）表达上调。腹腔内给予 Mel 可显著改善 MI/R 后的心脏功能并减少梗死面积，而 PVN 中 MT2 的 shRNA 沉默部分阻断了这种作用。腹腔内给予 Mel 可减轻 MI/R 引起的交感神经过度兴奋，而 PVN 中 MT2 的 shRNA 沉默部分减弱了这种作用。此外，酶联免疫吸附试验和 western blot 结果表明，腹腔内给予 Mel 可降低 MI/R 损伤后 PVN 中炎症细胞因子的水平，而在 PVN 中应用 sh-MT2 则降低了 Mel 的这种作用。Mel 可显著降低星形胶质细胞氧葡萄糖剥夺/复氧损伤后的 NF-κB 水平，而 MT2 沉默则抵消了这一作用。上述实验结果表明，PVN 中的 MT2 部分介导了 Mel 对 MI/R 损伤的保护作用，其潜在机制可能与改善 PVN 炎症后的后激活和减少心脏交感神经过度兴奋有关。
