Imperatorin Improves Obesity-Induced Cardiac Sympathetic Nerve Injury Mediated by P2X4 Receptor in Stellate Sympathetic Ganglion.
Imperatorin Improves Obesity-Induced Cardiac Sympathetic Nerve Injury Mediated by P2X4 Receptor in Stellate Sympathetic Ganglion.
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DOI：
10.3390/ijms24010783
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发表时间：
2023-01-02
影响因子：
5.6
通讯作者：
Gao Y
中科院分区：
文献类型：
--
作者：
Zhang M;Wen Y;Liang P;Yang C;Tu H;Wei J;Du J;Zhan T;Liang S;Li G;Gao Y
肥胖可激活炎症信号通路，诱发体内慢性炎症状态，交感神经系统兴奋性增加，可能诱发交感神经病理性损伤。星状交感神经节（SG）可表达P2X4受体，P2X4受体的异常表达与炎症有关。欧前胡素（IMP）是一种呋喃香豆素植物，具有抗炎作用。本项目旨在探讨IMP是否可以影响肥胖大鼠SG中P2X4受体的表达，从而对高脂肪引发的心脏交感神经损伤发挥保护作用。通过同源模型进行分子对接表明IMP对P2X4受体具有良好的亲和力。我们的结果显示，与正常组相比，给予IMP或P2X4 shRNA可降低交感神经兴奋；降低血清甘油三酯、总胆固醇和乳酸脱氢酶水平；下调 SG 中 P2X4 受体的表达；并显着抑制肥胖大鼠SG和血清中炎症因子的表达。此外，肥胖大鼠中与细胞焦亡相关的因子GSDMD、caspase-1、NLRP-3和IL-18的表达显着高于正常大鼠，且经IMP或P2X4 shRNA处理后这种影响减弱。此外，IMP 显着降低了转染 P2X4 受体的 HEK293 细胞中 ATP 激活的电流。因此，P2X4受体可能是治疗肥胖引起的心脏交感神经兴奋的关键靶点。 IMP可改善肥胖引起的心脏交感神经兴奋，其作用机制可能与抑制SG内P2X4受体表达和活性、抑制SG内细胞焦亡、降低炎症因子水平有关。
Obesity can activate the inflammatory signal pathway, induce in the body a state of chronic inflammation, and increase the excitability of the sympathetic nervous system, which may induce sympathetic neuropathic injury. The stellate sympathetic ganglia (SG) can express the P2X4 receptor, and the abnormal expression of the P2X4 receptor is related to inflammation. Imperatorin (IMP) is a kind of furan coumarin plant which has anti-inflammatory effects. This project aimed to investigate whether IMP can affect the expression of P2X4 receptors in the SG of obese rats to display a protective effect from high-fat-triggered cardiac sympathetic neuropathic injury. Molecular docking through homology modelling revealed that IMP had good affinity for the P2X4 receptor. Our results showed that compared with the normal group, the administration of IMP or P2X4 shRNA decreased sympathetic excitement; reduced the serum levels of triglyceride, total cholesterol, and lactate dehydrogenase; downregulated the expression of P2X4 receptors in SG; and inhibited the expression of inflammatory factors in the SG and serum of obese rats significantly. In addition, the expression of factors associated with the cell pyroptosis GSDMD, caspase-1, NLRP-3, and IL-18 in obese rats were significantly higher than those of the normal rats, and such effects were decreased after treatment with IMP or P2X4 shRNA. Furthermore, IMP significantly reduced the ATP-activated currents in HEK293 cells transfected with P2X4 receptor. Thus, the P2X4 receptor may be a key target for the treatment of obesity-induced cardiac sympathetic excitement. IMP can improve obesity-induced cardiac sympathetic excitement, and its mechanism of action may be related to the inhibition of P2X4 receptor expression and activity in the SG, suppression of cellular pyroptosis in the SG, and reduction of inflammatory factor levels.
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影响因子：
3.7
作者：
Cozzolino D;Grandone A;Cittadini A;Palmiero G;Esposito G;De Bellis A;Furlan R;Perrotta S;Perrone L;Torella D;Miraglia Del Giudice E
通讯作者：
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7.4
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