Microglial P2X7 receptor in the hypothalamic paraventricular nuclei contributes to sympathoexcitatory responses in acute myocardial infarction rat
Microglial P2X7 receptor in the hypothalamic paraventricular nuclei contributes to sympathoexcitatory responses in acute myocardial infarction rat
复制标题
下丘脑室旁核中的小胶质细胞 P2X7 受体有助于急性心肌梗死大鼠的交感兴奋反应
DOI：
10.1016/j.neulet.2014.12.026
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发表时间：
2015-02-05
影响因子：
2.5
通讯作者：
Zhu, Danian
中科院分区：
文献类型：
--
作者：
Du, Dongshu;Jiang, Meiyan;Zhu, Danian
一些证据表明，小胶质细胞的P2X(7)受体(P2X(7)R)调节心血管活动。我们探讨了小胶质细胞P2X(7)R在PVN介导的急性心肌梗死大鼠交感兴奋反应中的可能作用。采用冠状动脉结扎法制备大鼠急性心肌梗死模型。大鼠在心肌缺血前给予P2X(7)受体拮抗剂灿烂蓝G(BBG，25或50 mg·kg~(-1)，1次/d，连续5天)。另2组大鼠在心肌缺血前双侧室旁核微量注射靶向P2X(7)R-siRNA的P2X(7)R-siRNA(0.015或0.03nmol0.1亩L，1次/d，共2d)。首先，我们检测了不同缺血时间组PVN中的ATP水平和P2X(7)R的蛋白表达，发现P2X(7)R的变化与ATP水平呈时间依赖性的正相关。免疫荧光双标记法显示，P2X(7)R主要与小胶质细胞标记物LBA-1共定位于PVN。第二，用P2X(7)-siRNA基因敲除P2X(7)R或用BBG抑制P2X(7)R可降低急性心肌梗死大鼠PVN中IL-1β和TNF-α的mRNA和蛋白表达。第三，微量注射P2X(7)-siRNA还可抑制急性心肌梗死大鼠PVN中P2X(7)R、催产素和加压素的上调。第四，P2X(7)-siRNA和BBG对急性心肌梗死大鼠肾交感神经活动(RSNA)也有抑制作用。我们的结果表明，PVN内小胶质细胞P2X(7)R的激活介导了促炎细胞因子的产生，这些细胞因子激活了催产素能和加压素能神经元，从而增强了急性心肌梗死大鼠的RSNA。(C)2014爱思唯尔爱尔兰有限公司。保留所有权利。
Several pieces of evidence indicate that the microglial P2X(7) receptor (P2X(7)R) regulate cardiovascular activities. We explored the possible roles of microglial P2X(7)R in the PVN mediated sympathoexcitatory responses in acute myocardial infarction (AMI) rat. Sprague-Dawley rats underwent coronary artery ligation to induce AMI. The rats received intraperitoneal administration of the P2X(7)R antagonist Brilliant Blue-G (BBG, 25 or 50 mg kg(-1), once a day for 5 days) prior to myocardial ischemia. Other rats received bilateral microinjection of P2X(7)R-siRNA (0.015 or 0.03 nmol 0.1 mu l per side, once a day for 2 days) targeting P2X(7)R mRNA into the PVN prior to myocardial ischemia. First, we examined the ATP levels and protein expression P2X(7)R in the PVN in different ischemia time groups, and we found that the change of P2X(7)R was positive correlated with the ATP levels in a time-dependent manner. The double-immunofluorescence evidence showed that P2X(7)R was mainly co-localizated with the microglial marker lba-1 in the PVN. Second, gene knockdown of P2X(7)R with P2X(7)-siRNA or inhibition of P2X(7)R with BBG reduce the mRNA and protein expression of IL-1 beta and TNF-alpha in the PVN of AMI rat. Third, microinjected P2X(7)-siRNA also suppressed the up-regulation of P2X(7)R, oxytocin and vasopressin in the PVN of AMI rats. Fourth, P2X(7)-siRNA and BBG also attenuated the renal sympathetic nerve activity (RSNA) in the AMI rats. Our results indicate that microglial P2X(7)R activation in PVN mediating the production of proinflammatory cytokines that activate oxytocinergic and vasopressinergic neuron, which augmented the RSNA in the AMI rat. (C) 2014 Elsevier Ireland Ltd. All rights reserved.