Central blockade of NLRP3 reduces blood pressure via regulating inflammation microenvironment and neurohormonal excitation in salt-induced prehypertensive rats.
Central blockade of NLRP3 reduces blood pressure via regulating inflammation microenvironment and neurohormonal excitation in salt-induced prehypertensive rats.
复制标题
DOI：
10.1186/s12974-018-1131-7
复制
发表时间：
2018-03-24
影响因子：
9.3
通讯作者：
Yu XJ
中科院分区：
文献类型：
--
作者：
Wang ML;Kang YM;Li XG;Su Q;Li HB;Liu KL;Fu LY;Saahene RO;Li Y;Tan H;Yu XJ
炎症与心血管疾病的发展有关。本研究旨在探讨高血压前期的发病过程中是否存在P13样受体3（NLRP 3）的参与，阻断NLRP 3的中枢通路是否能减轻炎症反应，调节神经激素的兴奋，延缓高血压前期的发展。采用8%盐饮食诱导高血压前期大鼠。高盐饮食1个月的大鼠在下丘脑室旁核（PVN）给予特异性NLRP 3阻断剂4周。分别采用ELISA、Western blotting、免疫组织化学和流式细胞术检测NLRP 3级联蛋白、促炎细胞因子（PIC）、趋化因子配体2（CCL 2）、C-X-C趋化因子受体3（CXCR 3）、血管细胞粘附分子1（VCAM-1）、神经递质和白细胞计数。高血压前期大鼠室旁核NLRP 3表达明显增加，伴随小胶质细胞、CD 4+、CD 8 + T细胞和CD 8+小胶质细胞数量增加。PICs、CCL 2、CXCR 3和VCAM-1的表达显著增加。谷氨酸脱羧酶（GAD 67）和酪氨酸羟化酶（TH）之间的平衡被破坏。高血压前期大鼠血浆去甲肾上腺素（NE）升高，γ-氨基丁酸（GABA）降低。NLRP 3阻断显著降低血压，减少PVN中PIC、CCL 2、VCAM-1的表达，并恢复神经递质。血压和炎症标志物在中枢阻滞NLRP 3终止后上调。盐诱导的高血压前期部分是由于NLRP 3在PVN中的作用。阻断脑NLRP 3可能通过下调炎症引发的级联反应并恢复神经递质的平衡来减弱高血压前反应。本文的在线版本（10.1186/s12974-018-1131-7）包含补充材料，可供授权用户使用。
Inflammation has been implicated in the development of cardiovascular disease. We determined whether nod-like receptor with pyrin domain containing 3 (NLRP3) involved in the process of prehypertension, central blockade of NLRP3 decreased inflammation reaction, regulated neurohormonal excitation, and delayed the progression of prehypertension. Prehypertensive rats were induced by 8% salt diet. The rats on high-salt diet for 1 month were administered a specific NLRP3 blocker in the hypothalamic paraventricular nucleus (PVN) for 4 weeks. ELISA, western blotting, immunohistochemistry, and flow cytometry were used to measure NLRP3 cascade proteins, pro-inflammation cytokines (PICs), chemokine ligand 2 (CCL2), C-X-C chemokine receptor type 3 (CXCR3), vascular cell adhesion molecule 1 (VCAM-1), neurotransmitters, and leukocytes count detection, respectively. NLRP3 expression in PVN was increased significantly in prehypertensive rats, accompanied by increased number of microglia, CD4+, CD8+ T cell, and CD8+ microglia. Expressions of PICs, CCL2, CXCR3, and VCAM-1 significantly increased. The balance between 67-kDa isoform of glutamate decarboxylase (GAD67) and tyrosine hydroxylase (TH) was damaged. Plasma norepinephrine (NE) in prehypertensive rats was increased and gamma-aminobutyric acid (GABA) was reduced. NLRP3 blockade significantly decreased blood pressure, reduced PICs, CCL2, VCAM-1 expression in PVN, and restored neurotransmitters. Blood pressure and inflammatory markers were upregulated after termination of central blockage NLRP3. Salt-induced prehypertension is partly due to the role of NLRP3 in PVN. Blockade of brain NLRP3 attenuates prehypertensive response, possibly via downregulating the cascade reaction triggered by inflammation and restoring the balance of neurotransmitters. The online version of this article (10.1186/s12974-018-1131-7) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
7.8
作者：
Cassel SL;Joly S;Sutterwala FS
通讯作者：
Sutterwala FS
影响因子：
10.8
作者：
Dange, Rahul B.;Agarwal, Deepmala;Francis, Joseph
通讯作者：
Francis, Joseph
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
9.3
作者：
Dange RB;Agarwal D;Teruyama R;Francis J
通讯作者：
Francis J
脑核因子-κ B 激活有助于血管紧张素 II 诱导的高血压的神经体液兴奋
影响因子：
10.8
作者：
Kang, Yu-Ming;Ma, Ying;Francis, Joseph
通讯作者：
Francis, Joseph