Blockade of TLR4 Within the Paraventricular Nucleus Attenuates Blood Pressure by Regulating ROS and Inflammatory Cytokines in Prehypertensive Rats
Blockade of TLR4 Within the Paraventricular Nucleus Attenuates Blood Pressure by Regulating ROS and Inflammatory Cytokines in Prehypertensive Rats
复制标题
阻断室旁核内的 TLR4 通过调节高血压前期大鼠的 ROS 和炎症细胞因子来降低血压
DOI：
10.1093/ajh/hpy074
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发表时间：
2018-09-01
影响因子：
3.2
通讯作者：
Kang, Yu-Ming
中科院分区：
文献类型：
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作者：
Wang, Mo-Lin;Yu, Xiao-Jing;Kang, Yu-Ming
toll样受体4 （TLR4）与包括高血压在内的心血管疾病的进展有关。然而，TLR4在高血压前期发展中的作用尚不确定。方法采用8%盐治疗高血压大鼠12周，诱导高血压前期。然后给予这些大鼠TAK-242选择性TLR4阻滞剂或双侧微注射至室旁核（PVN）的载体。记录血压（BP）和肾交感神经活动。检测PVN中TLR4、髓样分化因子88 （Myd88）、核因子κ B (nf - κ B) p65、促炎细胞因子（PICs）、白细胞介素(IL)-1 β、IL-6、肿瘤坏死因子α (tnf - α)、烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶2 （NOX2）、NADPH氧化酶4 （NOX4）、Cu/Zn超氧化物歧化酶（SOD）水平、酪氨酸羟化酶、谷氨酸脱羧酶67 kDa亚型（GAD67）的表达，以确定TLR4阻断对PVN表达的影响。结果高盐组PVN中tstlr4表达显著升高，活性氧（ROS）和PICs相应升高。TLR4阻断可显著降低TLR4下游信号分子及tni -、IL-6、IL-1 β的表达，降低ROS、NOX2、NOX4水平，升高Cu/Zn-SOD，重新平衡神经递质，调节高血压前期大鼠PVN交感神经活动。结论盐诱导的高血压前期与PVN中TLR4的上调有关。大脑中TLR4的阻断降低了盐诱导的高血压前期反应，可能是通过下调ROS和PICs的表达，以及PVN中神经递质平衡的恢复。
BACKGROUNDToll-like receptor 4 (TLR4) has been implicated in the progression of cardiovascular disease, including hypertension. However, the role of TLR4 in the development of prehypertension is uncertain.METHODSPrehypertensive rats were treated with 8% salt for 12 weeks to induce prehypertension. These rats were then given either TAK-242 selective TLR4 blocker, or vehicle by bilateral micro-injection to the paraventricular nucleus (PVN). Blood pressure (BP) and renal sympathetic nerve activity were recorded. PVN expression of TLR4, myeloid differentiation factor 88 (Myd88), nuclear factor-kappa B (NF-kappa B) p65, proinflammation cytokines (PICs), interleukin (IL)-1 beta, IL-6, tumor necrosis factor-alpha (TNF-alpha), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2), NADPH oxidase 4 (NOX4), Cu/Zn superoxide dismutase (SOD) level, tyrosine hydroxylase, and 67 kDa isoform of glutamate decarboxylase (GAD67) were tested to determine the influence of TLR4 blockade.RESULTSTLR4 expression increased significantly in the PVN of high-salt groups with a corresponding increase in reactive oxygen species (ROS) and PICs. TLR4 blockade significantly reduced the signaling molecules downstream TLR4 and the expression ofTNI-, IL-6, IL-1 beta, decreased ROS, NOX2, NOX4 level, increased Cu/Zn-SOD, re-balanced neurotransmitters, and regulated sympathetic nerve activity in the PVN of prehypertensive rats.CONCLUSIONSSalt-induced prehypertension is partly due to the upregulation of TLR4 in PVN. Blockade of TLR4 in the brain reduced salt-induced prehypertension response, possibly through downregulation of ROS and PICs expression, and the restorage of neurotransmitter balance in the PVN.