|
|
- 2017
高血压中枢发病机制的研究进展
|
Abstract:
摘要：高血压是我国人群脑卒中及冠心病发病的首位危险因素，严重危害人群健康。目前，我国高血压患者已超过2.7亿，并以每年1000万人的速度递增，如何提高对高血压的预防和治疗水平已成为迫切需要解决的重大医学和社会问题。以往对于高血压的研究主要集中于外周。近来研究表明，中枢调控在高血压的发生发展中具有重要作用。其中下丘脑室旁核(hypothalamic paraventricular nucleus, PVN)在维持心血管活动中起着关键作用，可直接支配交感神经节前神经元，参与外周交感神经活动的调节，并与高血压的发生发展密切相关。近年来研究表明，室旁核中炎性细胞因子(proinflammatory cytokines, PIC)、活性氧簇(reactive oxygen species, ROS)、肾素-血管紧张素系统(renin-angiotensin system, RAS)、神经递质(neurotransmitter, NT)及核因子κB(nuclear factor κB, NF-κB)等神经激素参与高血压的病理生理过程，但室旁核中这些神经激素如何激活、相互间的作用以及对高血压的调控机制尚不清楚。因此，探明下丘脑室旁核神经激素兴奋对高血压的影响是本课题的研究重点。本研究将为高血压的中枢机制研究补充新内容。
ABSTRACT: Hypertension, the first risk factor for stroke and coronary heart disease in the Chinese population, seriously endangers people’s health. At present, China has more than 270 million people with hypertension and an annual increase rate of 10 million people. Then how to improve prevention and treatment of hypertension has become an urgent need to solve major medical and social problems. In the past, research on hypertension mainly focused on the peripheral area, while recent research has shown that the central regulation plays an important role in the development of hypertension. Hypothalamic paraventricular nucleus (PVN), which plays a key role in maintaining cardiovascular activity, can directly control the sympathetic preganglionic neurons and regulate peripheral sympathetic nerve activity, thus being closely related to the development of hypertension. Research in recent years shows that the comprehensive effects of proinflammatory cytokines (PIC), reactive oxygen species (ROS), renin-angiotensin system (RAS), neurotransmitter (NT) and nuclear factor κB (NF-κB) are involved in the pathogenesis of hypertension. However, it is unclear how these neurohormones in PVN are activated, how they interact with each other and what role they play in the regulatory mechanism of hypertension. Therefore, the key focus of this research is to explore the impact of activated neurohormones in PVN on hypertension. This study will provide new content for the study on hypertension
| [1] | SRIRAMULA S, FRANCIS J. Tumor necrosis factor-alpha is essential for angiotensin ii-induced ventricular remodeling: Role for oxidative stress[J]. PLoS One, 2015, 10(9):e0138372. |
| [2] | SU Q, LIU JJ, CUI W, et al. Alpha lipoic acid supplementation attenuates reactive oxygen species in hypothalamic paraventricular nucleus and sympathoexcitation in high salt-induced hypertension[J]. Toxicol Lett, 2016, 241:152-158. |
| [3] | GABOR A, LEENEN FH. Mechanisms mediating sodium-induced pressor responses in the PVN of Dahl rats[J]. Am J Physiol Regul Integr Comp Physiol, 2011, 301(5):R1338-1349. |
| [4] | SU Q, QIN DN, WANG FX, et al. Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin-angiotensin system and proinflammatory cytokines in hypertension[J]. Toxicol Appl Pharmacol, 2014, 276(2):115-120. |
| [5] | KANG YM, ZHANG AQ, ZHAO XF, et al. Paraventricular nucleus corticotrophin releasing hormone contributes to sympathoexcitation via interaction with neurotransmitters in heart failure[J]. Basic Res Cardiol, 2011, 106(3):473-483. |
| [6] | LI HB, QIN DN, SUO YP, et al. Blockade of salusin-beta in hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy in salt-induced hypertensive rats[J]. J Cardiovasc Pharmacol, 2015, 66(4):323-331. |
| [7] | (NF-kappab) transcription factor[J]. Mol Cell Biochem, 2000, 212(1-2):155-169. |
| [8] | YU XJ, ZHANG DM, JIA LL, et al. Inhibition of NF activity in the hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by modulating cytokines and attenuating oxidative stress[J]. Toxicol Appl Pharmacol, 2015, 284(3):315-322. |
| [9] | KANG YM, ZHANG DM, YU XJ, et al. Chronic infusion of enalaprilat into hypothalamic paraventricular nucleus attenuates angiotensin ii-induced hypertension and cardiac hypertrophy by restoring neurotransmitters and cytokines[J]. Toxicol Appl Pharmacol, 2014, 274(3):436-444. |
| [10] | WEI SG, YU Y, ZHANG ZH, et al. Proinflammatory cytokines upregulate sympathoexcitatory mechanisms in the subfornical organ of the rat[J]. Hypertension, 2015, 65(5):1126-1133. |
| [11] | XUE B, THUNHORST RL, YU Y, et al. Central renin-angiotensin system activation and inflammation induced by high-fat diet sensitize angiotensin ii-elicited hypertension[J]. Hypertension, 2016, 67(1):163-170. |
| [12] | LI HB, QIN DN, MA L, et al. Chronic infusion of lisinopril into hypothalamic paraventricular nucleus modulates cytokines and attenuates oxidative stress in rostral ventrolateral medulla in hypertension[J]. Toxicol Appl Pharmacol, 2014, 279(2):141-149. |
| [13] | LI HB, LU Y, LIU JJ, et al. Salusin beta within the nucleus tractus solitarii suppresses blood pressure via inhibiting the activities of presympathetic neurons in the rostral ventrolateral medulla in spontaneously hypertensive rats[J]. Cardiovasc Toxicol, 2016, 16(3):223-234. |
| [14] | KANG YM, MA Y, ZHENG JP, et al. Brain nuclear factor-kappa b activation contributes to neurohumoral excitation in angiotensin ii-induced hypertension[J]. Cardiovasc Res, 2009, 82(3):503-512. |
| [15] | ZHU L, CARRETERO OA, XU J, et al. Activation of angiotensin Ⅱ type 2 receptor suppresses TNF-α-induced ICAM-1 via NF-кB: possible role of ACE2[J]. Am J Physiol Heart Circ Physiol, 2015, 309(5):H827-834. |
| [16] | DE KLOET AD, PITRA S, WANG L, et al. Angiotensin type-2 receptors influence the activity of vasopressin neurons in the paraventricular nucleus of the hypothalamus in male mice[J]. Endocrinology, 2016, 157(8):3167-3180. |
| [17] | GABOR A, LEENEN FH. Central neuromodulatory pathways regulating sympathetic activity in hypertension[J]. J Appl Physiol (1985), 2012, 113(8):1294-1303. |
| [18] | VIEIRA AA, COLOMBARI E, DE LUCA LA JR, et al. Cardiovascular responses to injections of angiotensin ii or carbachol into the rostral ventrolateral medulla in rats with AV3V lesions[J]. Neurosci Lett, 2013, 556:32-36. |
| [19] | WANG R, HUANG Q, ZHOU R, et al. Sympathoexcitation in rats with chronic heart failure depends on homeobox d10 and microrna-7b inhibiting gabbr1 translation in paraventricular nucleus[J]. Circ Heart Fail, 2016, 9(1):e002261. |
| [20] | DANGE RB, AGARWAL D, TERUYAMA R, et al. Toll-like receptor 4 inhibition within the paraventricular nucleus attenuates blood pressure and inflammatory response in a genetic model of hypertension[J]. J Neuroinflammation, 2015, 12:31. |
| [21] | WANG G, COLEMAN CG, CHAN J, et al. Angiotensin ii slow-pressor hypertension enhances NMDA currents and COX2-dependent superoxide production in hypothalamic paraventricular neurons[J]. Am J Physiol Regul Integr Comp Physiol, 2013, 304(12):R1096-1106. |
| [22] | SONG XA, JIA LL, CUI W, et al. Inhibition of TNF-alpha in hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by inhibiting neurohormonal excitation in spontaneously hypertensive rats[J]. Toxicol Appl Pharmacol, 2014, 281(1):101-108. |
| [23] | KANG YM, WANG Y, YANG LM, et al. TNF-alpha in hypothalamic paraventricular nucleus contributes to sympathoexcitation in heart failure by modulating at1 receptor and neurotransmitters[J]. Tohoku J Exp Med, 2010, 222(4):251-263. |
| [24] | BARDGETT ME, HOLBEIN WW, HERRERA-ROSALES M, et al. Ang ii-salt hypertension depends on neuronal activity in the hypothalamic paraventricular nucleus but not on local actions of tumor necrosis factor-alpha[J]. Hypertension, 2014, 63(3):527-534. |
| [25] | ZHANG Q, YAO F, O’ROURKE ST, et al. Angiotensin ii enhances GABA(B) receptor-mediated responses and expression in nucleus tractus solitarii of rats[J]. Am J Physiol Heart Circ Physiol, 2009, 297(5):H1837-1844. |
| [26] | LI HL, KANG YM, YU L, et al. Melatonin reduces blood pressure in rats with stress-induced hypertension via GABAA receptors[J]. Clin Exp Pharmacol Physiol, 2009, 36(4):436-440. |
| [27] | DA SILVA AQ, FONTES MA, KANAGY NL. Chronic infusion of angiotensin receptor antagonists in the hypothalamic paraventricular nucleus prevents hypertension in a rat model of sleep apnea[J]. Brain Res, 2011, 1368:231-238. |
| [28] | ZUCKER IH, SCHULTZ HD, PATEL KP, et al. Modulation of angiotensin ii signaling following exercise training in heart failure[J]. Am J Physiol Heart Circ Physiol, 2015, 308(8):H781-791. |
| [29] | COLLISTER JP, TAYLOR-SMITH H, DREBES D, et al. Angiotensin ii-induced hypertension is attenuated by overexpressing copper/zinc superoxide dismutase in the brain organum vasculosum of the lamina terminalis[J]. Oxid Med Cell Longev, 2016, 2016:3959087. |
| [30] | BRASIER AR, JAMALUDDIN M, HAN Y, et al. Angiotensin ii induces gene transcription through cell-type-dependent effects on the nuclear factor-kappab |
| [31] | GAO HL, YU XJ, QI J, et al. Oral CoQ10 attenuates high salt-induced hypertension by restoring neurotransmitters and cytokines in the hypothalamic paraventricular nucleus[J]. Sci Rep, 2016, 6:30301. |
| [32] | CARMICHAEL CY, WAINFORD RD. Hypothalamic signaling mechanisms in hypertension[J]. Curr Hypertens Rep, 2015, 17(5):39. |
| [33] | DANGE RB, AGARWAL D, MASSON GS, et al. Central blockade of tlr4 improves cardiac function and attenuates myocardial inflammation in angiotensin ii-induced hypertension[J]. Cardiovasc Res, 2014, 103(1):17-27. |
| [34] | ZHANG M, QIN DN, SUO YP, et al. Endogenous hydrogen peroxide in the hypothalamic paraventricular nucleus regulates neurohormonal excitation in high salt-induced hypertension[J]. Toxicol Lett, 2015, 235(3):206-215. |
| [35] | LI HB, QIN DN, CHENG K, et al. Central blockade of salusin beta attenuates hypertension and hypothalamic inflammation in spontaneously hypertensive rats[J]. Sci Rep, 2015, 5:11162. |
| [36] | KANG YM, GAO F, LI HH, et al. NF-kappab in the paraventricular nucleus modulates neurotransmitters and contributes to sympathoexcitation in heart failure[J]. Basic Res Cardiol, 2011, 106(6):1087-1097. |
| [37] | DU D, CHEN J, LIU M, et al. The effects of angiotensin ii and angiotensin-(1-7) in the rostral ventrolateral medulla of rats on stress-induced hypertension[J]. PLoS One, 2013, 8(8):e70976. |
