Chronic lead exposure enhances the sympathoexcitatory response associated with P2X4 receptor in rat stellate ganglia
Chronic lead exposure enhances the sympathoexcitatory response associated with P2X4 receptor in rat stellate ganglia
复制标题
慢性铅暴露增强大鼠星状神经节中与 P2X4 受体相关的交感兴奋反应
DOI：
10.1002/tox.22547
复制
发表时间：
2018
影响因子：
4.5
通讯作者：
Li Guilin
中科院分区：
文献类型：
--
作者：
Zhu Gaochun;Chen Zhenying;Dai Bo;Zheng Chaoran;Jiang Huaide;Xu Yurong;Sheng Xuan;Guo Jingjing;Dan Yu;Liang Shangdong;Li Guilin
慢性铅暴露会刺激周围交感神经，包括血压升高和心率加快。嘌呤能受体参与心肌缺血损伤引起的交感兴奋反应。然而，P2X4受体是否参与慢性铅暴露引起的交感兴奋反应及其可能的机制尚不清楚。本研究的目的是探讨慢性铅暴露通过星状神经节（SG）中的P2X4受体引起的交感兴奋反应的变化。大鼠通过自由饮水给予醋酸铅0 g/L（对照组）、0.5 g/L（低铅组）和2 g/L（高铅组）剂量1年。我们的结果表明，铅暴露会导致自主神经功能障碍，包括血压和心率升高以及心率变异性（HRV）降低。 Western blotting结果表明，铅暴露后，SG中P2X4受体、IL-1β和Cx43蛋白表达水平上调，p38丝裂原激活蛋白激酶（MAPK）磷酸化被激活。实时PCR结果显示，铅暴露组SG中P2X4受体mRNA表达量高于对照组。双标记免疫荧光结果显示，P2X4受体与卫星胶质细胞（SGC）标记物谷氨酰胺合成酶（GS）共表达。这些变化与铅暴露剂量呈正相关。 SG 的 SGC 中 P2X4 受体表达上调可能增强慢性铅暴露引起的交感兴奋反应。
Chronic lead exposure causes peripheral sympathetic nerve stimulation, including increased blood pressure and heart rate. Purinergic receptors are involved in the sympathoexcitatory response induced by myocardial ischemia injury. However, whether P2X4 receptor participates in sympathoexcitatory response induced by chronic lead exposure and the possible mechanisms are still unknown. The aim of this study was to explore the change of the sympathoexcitatory response induced by chronic lead exposure via the P2X4 receptor in the stellate ganglion (SG). Rats were given lead acetate through drinking water freely at doses of 0 g/L (control group), 0.5 g/L (low lead group), and 2 g/L (high lead group) for 1 year. Our results demonstrated that lead exposure caused autonomic nervous dysfunction, including blood pressure and heart rate increased and heart rate variability (HRV) decreased. Western blotting results indicated that after lead exposure, the protein expression levels in the SG of P2X4 receptor, IL‐1β and Cx43 were up‐regulated, the phosphorylation of p38 mitogen‐activated protein kinase (MAPK) was activated. Real‐time PCR results showed that the mRNA expression of P2X4 receptor in the SG was higher in lead exposure group than that in the control group. Double‐labeled immunofluorescence results showed that P2X4 receptor was co‐expressed with glutamine synthetase (GS), the marker of satellite glial cells (SGCs). These changes were positively correlated with the dose of lead exposure. The up‐regulated expression of P2X4 receptor in SGCs of the SG maybe enhance the sympathoexcitatory response induced by chronic lead exposure.