针刺太冲、太溪对自发性高血压大鼠下丘脑病理形态的影响
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摘要
目的:通过观察针刺太冲、太溪后自发性高血压大鼠的下丘脑HE染色、尼氏染色及两者的半定量等指标。探讨课题前期功能磁共振结果在分子生物学层面的机制。最终,尝试寻求针刺对自发性高血压大鼠的降压机制,为阐明针灸降低血压的原理提供理论和实验依据。方法:采用STATA 14.0统计软件以原始血压为分层条件按照随机区组设计将SHRs随机分成3组:模型组、冲溪组、非穴组,每组12只。WKY大鼠不分组。针灸处方:太冲(双)、太溪(双)、非穴(双)。操作方法:在大鼠清醒状态下行针刺捻转手法,平补平泻,于每天上午8∶30开始进行,左右两侧穴位同时进行针刺,直刺,先左侧穴位行针2.5 min,然后右侧穴位行针2.5 min,每次持续总共时间5 min,针刺每日1次,逢周日休息1 d,连续针刺4周,共针刺24次。捻转频率为(80±5)次/min,捻转幅度(180±5)°。所有针刺操作由固定一人进行。正常组与模型组不给予针刺,抓取固定5 min。采用HE染色和尼氏染色观察大鼠下丘脑的一般病理形态结构;采用ImageJ对细胞数量进行半定量计算。结果:各组大鼠下丘脑HE染色及尼氏染色后所得病理结果与同脑区正常组相比较,未观察到明显的病理变化。但相较于正常组,其余各组细胞总数及尼氏体数量均有不同程度减少。通过半定量方式进行证实。细胞总数及尼氏体数量从多到少依次是:正常组、冲溪组、非穴组、模型组。结论:针刺太冲、太溪对SHRs降压作用在病理形态学上的可能机制在于减少或阻止下丘脑的细胞减少和凋亡,解除细胞增殖能力的抑制,对N-甲基-D-天冬氨酸(NMDA)受体信号传导的调节,调整下丘脑室旁核肾上腺髓质素含量水平、调节Toll样受体4(Toll-like receptor 4,TLR4)所参与的促炎细胞因子生成及脑源性神经营养因子(BDNF)的含量水平而实现下丘脑的保护。最终通过上述多种机制,而使得一系列与下丘脑相关的血压调控途径得到调整,实现降压目的。
Objective:To observe the hypothalamic HE staining and Nissl staining of spontaneously hypertensive rats after acupuncture at Taichong(LR3) and Taixi(KI3). To discuss topics preliminary results of functional magnetic resonance mechanism in molecular biology level and try to seek the antihypertensive mechanism of acupuncture on spontaneously hypertensive ratsand provide the theoretical and experimental basis for elucidating the principle of acupuncture to lower blood pressure.Methods:By STAT 14.0, the SHRs were randomly divided into three groups according to the randomized block design using the original blood pressure as the stratification condition: Model group, Chongxi group and Sham acupuncture group, 12 in each group. WKY rats were not grouped. Acupuncture prescriptions: Tai Chong(double,LR3), Taixi double,KI3), non-acupoint(double). Method of operation: Acupuncture in the awake state of the rats by gentle tonifying and purging manipulation, starting at 8∶30 everyday. Both sides were needled at the same time. First the left side was needled for 2.5 mins and then the the right side was needled for 2.5 mins, totally lasting for 5 mins, once a day. There was a rest on Sunday. The acupuncture was lasted for 4 weeks, a total of 24 times. The twisting frequency was(80±5)times/min, and the twisting amplitude was(180±5)°. All acupuncture operations were performed by the same person. The normal group and the model group were not given acupuncture, and the grasping was fixed for 5 min. The general pathological morphology of the rat hypothalamus was observed by HE staining and Nissl staining. The number of cells was semi-quantitatively calculated using ImageJ.Results:HE staining and hypothalamus of rats after Nissl pathology results obtained the same brain regions as compared to the normal group and no significant pathological changes were observed. However, compared with the normal group, the total number of cells and the number of Nissl bodies in the other groups were reduced to some extent. Confirmed by semi-quantitative means,the total number of cells and the number of Nissl bodies from high to low were normal group, Chongxi group, Sham acupuncture group and model group.Conclusion: The possible mechanism of acupuncture at Taichong(LR3) and Taixi(KI3) on the pathological morphology of antihypertensive effect of SHRs is to reduce or prevent cell reduction and apoptosis of hypothalamus, and abolish the inhibition of cell proliferation, for N-methyl-D-Regulation of aspartate(NMDA) receptor signaling, regulation of hypothalamic paraventricular nucleus adrenomedullin levels, regulation of pro-inflammatory cytokines involved in Toll-like receptor 4(TLR4). The level of brain-derived neurotrophic factor(BDNF) is produced to achieve protection of the hypothalamus. Finally, through a variety of mechanisms described above, a series of blood pressure regulation pathways related to the hypothalamus are adjusted to achieve the purpose of blood pressure reduction.
Objective:To observe the hypothalamic HE staining and Nissl staining of spontaneously hypertensive rats after acupuncture at Taichong(LR3) and Taixi(KI3). To discuss topics preliminary results of functional magnetic resonance mechanism in molecular biology level and try to seek the antihypertensive mechanism of acupuncture on spontaneously hypertensive ratsand provide the theoretical and experimental basis for elucidating the principle of acupuncture to lower blood pressure.Methods:By STAT 14.0, the SHRs were randomly divided into three groups according to the randomized block design using the original blood pressure as the stratification condition: Model group, Chongxi group and Sham acupuncture group, 12 in each group. WKY rats were not grouped. Acupuncture prescriptions: Tai Chong(double,LR3), Taixi double,KI3), non-acupoint(double). Method of operation: Acupuncture in the awake state of the rats by gentle tonifying and purging manipulation, starting at 8∶30 everyday. Both sides were needled at the same time. First the left side was needled for 2.5 mins and then the the right side was needled for 2.5 mins, totally lasting for 5 mins, once a day. There was a rest on Sunday. The acupuncture was lasted for 4 weeks, a total of 24 times. The twisting frequency was(80±5)times/min, and the twisting amplitude was(180±5)°. All acupuncture operations were performed by the same person. The normal group and the model group were not given acupuncture, and the grasping was fixed for 5 min. The general pathological morphology of the rat hypothalamus was observed by HE staining and Nissl staining. The number of cells was semi-quantitatively calculated using ImageJ.Results:HE staining and hypothalamus of rats after Nissl pathology results obtained the same brain regions as compared to the normal group and no significant pathological changes were observed. However, compared with the normal group, the total number of cells and the number of Nissl bodies in the other groups were reduced to some extent. Confirmed by semi-quantitative means,the total number of cells and the number of Nissl bodies from high to low were normal group, Chongxi group, Sham acupuncture group and model group.Conclusion: The possible mechanism of acupuncture at Taichong(LR3) and Taixi(KI3) on the pathological morphology of antihypertensive effect of SHRs is to reduce or prevent cell reduction and apoptosis of hypothalamus, and abolish the inhibition of cell proliferation, for N-methyl-D-Regulation of aspartate(NMDA) receptor signaling, regulation of hypothalamic paraventricular nucleus adrenomedullin levels, regulation of pro-inflammatory cytokines involved in Toll-like receptor 4(TLR4). The level of brain-derived neurotrophic factor(BDNF) is produced to achieve protection of the hypothalamus. Finally, through a variety of mechanisms described above, a series of blood pressure regulation pathways related to the hypothalamus are adjusted to achieve the purpose of blood pressure reduction.
引文
[1] 黄汉菊, 卢建雄, 杨月嫦. 缬沙坦联合氨氯地平治疗社区原发性高血压的临床疗效及安全性 [J].中国老年学杂志, 2013, 33(9):2154-2155.
[2] 明少菊, 侯超, 周芳.缬沙坦治疗原发性高血压合并 2 型糖尿病对血压及肾功能的影响 [J].中国老年学杂志, 2013, 33(18):4421-4422.
[3] Wang J, Zhang L, Wang F, et al.China National Survey of Chronic Kidney Disease Working Group.Prevalence, awareness, treatment, and control of hypertension in China:Results from a national survey[J].Am J Hypertens, 2014, 27(11):1355-1361.
[4] Sun NL, Huo Y, Wang JG, et al.Consensus of Chinese specialists on diagnosis and treatment of resistant hypertension[J].Chin Med J (Engl), 2015, 128(5):2102-2108.
[5] Nagai M, Hoshide S, Kario K.The insular cortex and cardiovascular system:a new insight into the brain-heart axis[J].J Am Soc Hypertens, 2010, 4(4): 174-182.
[6] 李耀华, 吴建新, 周萍, 等.大鼠外侧隔在中央杏仁核情绪升压系统中作用的实验研究[J].医学研究杂志, 2008, 37(3):38-42.
[7] Barboriak DP, Padua AO, York GE, et al.Creation of DICOM--aware applications using ImageJ[J].J Digit Imaging, 2005, 18(2):91-99.
[8] Avino TA, Barger N, Vargas MV, et al.Neuron numbers increase in the human amygdala from birth to adulthood, but not in autism[J].Proc Natl Acad Sci USA, 2018(5):201801912.
[9] Robertson BA, Rathbone L, Cirillo G, et al.Food restriction reduces neurogenesis in the avian hippocampal formation[J].PLoS One, 2017, 12(12):e0189158.
[10] Boucherie C, Boutin C, Jossin Y, et al.Neural progenitor fate decision defects, cortical hypoplasia and behavioral impairment in Celsr1-deficient mice[J].Mol Psychiatry, 2018, 23(3):723-734.
[11] Rajkowska G, Miguel-Hidalgo JJ.Gliogenesis and glial pathology in depression[J].CNS Neurol Disord Drug Targets, 2007, 6(3):219-233.
[12] Ferguson AV, Latchford KJ, Samson WK.The paraventricular nucleus of the hypothalamus-a potential target for integrative treatment of autonomic dysfunction[J].Expert Opin Ther Targets, 2008, 12(6):717-727.
[13] Eyigor O, Centers A, Jennes L.Distribution of ionotropic glutamate receptor subunit mRNAs in the rat hypothalamus[J].J Comp Neurol, 2001, 434(1):101-124.
[14] Petralia RS, Yokotani N, Wenthold RJ.Light and electron microscope distribution of the NMDA receptor subunit NMDAR1 in the rat nervous system using a selective anti-peptide antibody[J].J Neurosci, 1994, 14(2):667-696.
[15] Li DP, Byan HS, Pan HL.Switch to glutamate receptor 2-lacking AMPA receptors increases neuronal excitability in hypothalamus and sympathetic drive in hypertension[J].J Neurosci, 2012, 32(1):372-380.
[16] Marques-Lopes J, Van Kempen T, Waters EM, et al.Slow-pressor angiotensin II hypertension and concomitant dendritic NMDA receptor trafficking in estrogen receptor beta–containing neurons of the mouse hypothalamic paraventricular nucleus are sex and age dependent[J].J Comp Neurol, 2014, 522(13):3075-3090.
[17] Coleman CG, Wang G, Faraco G, et al.Membrane trafficking of NADPH oxidase p47(phox) in paraventricular hypothalamic neurons parallels local free radical production in angiotensin II slow-pressor hypertension[J].J Neurosci, 2013, 33(10):4308-4316.
[18] Garthwaite J.Concepts of neural nitric oxide-mediated transmission[J].Eur J Neurosci, 2008, 27(11):2783-2802.
[19] Wang G, Coleman CG, Chan J, et al.Angiotensin II slow-pressor hypertension enhances NMDA currents and NOX2-dependent superoxide production in hypothalamic paraventricular neurons[J].Am J Physiol Regul Integr Comp Physiol, 2013, 304(12):R1096-1106.
[20] 李霞, 李良, 樊明欣, 等.应激性血压升高对大鼠下丘脑肾上腺髓质素水平的影响[J].中国动脉硬化杂志, 2009, 17(5):354-358.
[21] Romero JC, Reckelhoff JF.State-of-the-Art lecture.Role of angiotensin and oxidative stress in essential hypertension[J].Hypertension, 1999, 34(4 Pt 2):943-949.
[22] Young CN, Cao X, Guruju MR, et al.ER stress in the brain subfornical organ mediates angiotensin-dependent hypertension[J].J Clin Invest, 2012, 122(11):3960-3964.
[23] 藏好晶.经下丘脑室旁核给予NF-κB抑制剂PDTC对高血压大鼠血压的影响及其机制的研究[D].太原:山西医科大学, 2013.
[24] Cato MJ, Toney GM.Angiotensin II excites paraventricular nucleus neurons that innervate the rostral ventrolateral medulla:an in vitro patch-clamp study in brain slices[J].J Neurophysiol, 2005, 93(1):403-413.
[25] Larson RA, Gui L, Huber MJ, et al.Sympathoexcitation in ANG II-salt hypertension involves reduced SK channel function in the hypothalamic paraventricular nucleus[J].Am J Physiol Heart Circ Physiol, 2015, 308(12):H1547-1551.
[26] Latchford KJ, Ferguson AV.Angiotensin depolarizes parvocellular neurons in paraventricular nucleus through modulation of putative nonselective cationic and potassium conductances[J].Am J Physiol Regul Integr Comp Physiol, 2005, 289(1):R52-58.
[27] Egli M, Berger T, Imboden H.Angiotensin II influences the hyperpolarization-activated current Ih in neurones of the rat paraventricular nucleus[J].Neurosci Lett, 2002, 330(1):53-56.
[28] Latchford KJ, Ferguson AV.Angiotensin II activates a nitric-oxide-driven inhibitory feedback in the rat paraventricular nucleus[J].J Neurophysiol, 2003, 89(3):1238-1244.
[29] Antunes VR, Yao ST, Pickering AE, et al.A spinal vasopressinergic mechanism mediates hyperosmolality‐induced sympathoexcitation[J].J Physiol, 2006, 576(Pt 2):569-583.
[30] Stocker SD, Keith KJ, Toney GM.Acute inhibition of the hypothalamic paraventricular nucleus decreases renal sympathetic nerve activity and arterial blood pressure in water-deprived rats[J].Am J Physiol Regul Integr Comp Physiol, 2004, 286(4):R719-725.
[31] Ferguson AV, Latchford KJ, Samson WK.The paraventricular nucleus of the hypothalamus–a potential target for integrative treatment of autonomic dysfunction[J].Expert Opin Ther Targets, 2008, 12(6):717-727.
[32] Leow-Dyke S, Allen C, Denes A, et al.Neuronal Toll-like receptor 4 signaling induces brain endothelial activation and neutrophil transmigration in vitro[J].J Neuroinflammation, 2012, 9:230.
[33] Medzhitov R, Preston-Hurlburt P, Janeway CA. Jr A human homologue of the Drosophila Toll protein signals activation of adaptive immunity[J].Nature, 1997, 388(6640):394-397.
[34] Rock FL, Hardiman G, Timans JC, et al.A family of human receptors structurally related to Drosophila Toll[J].Proc Natl Acad Sci USA, 1998, 95(2):588-593.
[35] Piccinini AM, Midwood KS.DAM Pening inflammation by modulating TLR signalling[J].Mediators Inflamm, 2010(10):1-21.
[36] Cardinale JP, Sriramula S, Mariappan N, et al.Angiotensin II-induced hypertension is modulated by nuclear factor-kappaBin the paraventricular nucleus[J].Hypertension, 2012, 59(1):113-121.
[37] Shi Z, Gan XB, Fan ZD, et al.Inflammatory cytokines in paraventricular nucleus modulate sympathetic activity and cardiac sympathetic afferent reflex in rats[J].Acta Physiol (Oxf), 2011, 203(2):289-297.
[38] Agarwal D, Elks CM, Reed SD, et al.Chronic exercise preserves renal structure and hemodynamics in spontaneously hypertensive rats[J].Antioxid Redox Signal, 2012, 16(2):139-152.
[39] Huang EJ, Reichardt LF.Neurotrophins:roles in neuronal development and function[J].Annu Rev Neurosci, 2001, 24:677-736.
[40] Poo MM.Neurotrophins as synaptic modulators[J].Nat Rev Neurosci, 2001, 2(1):24-32.
[41] Amaral MD, Pozzo-Miller L.BDNF induces calcium elevations associated with IBDNF, a nonselective cationic current mediated by TRPC channels[J].J Neurophysiol, 2007, 98(4):2476-2482.
[42] Jeanneteau FD, Lambert WM, Ismaili N, et al.BDNF and glucocorticoids regulate corticotrophin-releasing hormone (CRH) homeostasis in the hypothalamus[J].Proc Natl Acad Sci USA, 2012, 109(4):1305-1310.
[43] Lebrun B, Bariohay B, Moyse E, et al.Brain-derived neurotrophic factor (BDNF) and food intake regulation:a minireview[J].Auton Neurosci, 2006(126-127):30-38.
[44] Rosas-Vargas H, Martinez-Ezquerro JD, Bienvenu T.Brain-derived neurotrophic factor, food intake regulation, and obesity[J].Arch Med Res, 2011, 42(6):482-494.
[45] Toriya M, Maekawa F, Maejima Y, et al.Long-term infusion of brain-derived neurotrophic factor reduces food intake and body weight via a corticotrophin-releasing hormone pathway in the paraventricular nucleus of the hypothalamus[J].J Neuroendocrinol, 2010, 22(9):987-995.
[46] Hammack SE, Cheung J, Rhodes KM, et al.Chronic stress increases pituitary adenylate cyclase-activating peptide (PACAP) and brain-derived neurotrophic factor (BDNF) mRNA expression in the bed nucleus of the stria terminalis (BNST):roles for PACAP in anxiety-like behavior[J].Psychoneuroendocrinology, 2009, 34(6):833-843.
[47] Aliaga E, Arancibia S, Givalois L, et al.Osmotic stress increases brain-derived neurotrophic factor messenger RNA expression in the hypothalamic supraoptic nucleus with differential regulation of its transcripts relation to arginine-vasopressin content[J].Neuroscience, 2002, 112(4):841-850.
[48] Meredith GE, Callen S, Scheuer DA.Brain-derived neurotrophic factor expression is increased in the rat amygdala, piriform cortex and hypothalamus following repeated amphetamine administration[J].Brain Res, 2002, 949(1-2):218-227.
[49] 姬彩硕.针刺对自发性高血压大鼠下丘脑室旁核炎症因子含量及TLR4表达水平的影响[C]//世界针灸学术大会暨2017中国针灸学会年会论文集.中国针灸学会,2017:2.
[2] 明少菊, 侯超, 周芳.缬沙坦治疗原发性高血压合并 2 型糖尿病对血压及肾功能的影响 [J].中国老年学杂志, 2013, 33(18):4421-4422.
[3] Wang J, Zhang L, Wang F, et al.China National Survey of Chronic Kidney Disease Working Group.Prevalence, awareness, treatment, and control of hypertension in China:Results from a national survey[J].Am J Hypertens, 2014, 27(11):1355-1361.
[4] Sun NL, Huo Y, Wang JG, et al.Consensus of Chinese specialists on diagnosis and treatment of resistant hypertension[J].Chin Med J (Engl), 2015, 128(5):2102-2108.
[5] Nagai M, Hoshide S, Kario K.The insular cortex and cardiovascular system:a new insight into the brain-heart axis[J].J Am Soc Hypertens, 2010, 4(4): 174-182.
[6] 李耀华, 吴建新, 周萍, 等.大鼠外侧隔在中央杏仁核情绪升压系统中作用的实验研究[J].医学研究杂志, 2008, 37(3):38-42.
[7] Barboriak DP, Padua AO, York GE, et al.Creation of DICOM--aware applications using ImageJ[J].J Digit Imaging, 2005, 18(2):91-99.
[8] Avino TA, Barger N, Vargas MV, et al.Neuron numbers increase in the human amygdala from birth to adulthood, but not in autism[J].Proc Natl Acad Sci USA, 2018(5):201801912.
[9] Robertson BA, Rathbone L, Cirillo G, et al.Food restriction reduces neurogenesis in the avian hippocampal formation[J].PLoS One, 2017, 12(12):e0189158.
[10] Boucherie C, Boutin C, Jossin Y, et al.Neural progenitor fate decision defects, cortical hypoplasia and behavioral impairment in Celsr1-deficient mice[J].Mol Psychiatry, 2018, 23(3):723-734.
[11] Rajkowska G, Miguel-Hidalgo JJ.Gliogenesis and glial pathology in depression[J].CNS Neurol Disord Drug Targets, 2007, 6(3):219-233.
[12] Ferguson AV, Latchford KJ, Samson WK.The paraventricular nucleus of the hypothalamus-a potential target for integrative treatment of autonomic dysfunction[J].Expert Opin Ther Targets, 2008, 12(6):717-727.
[13] Eyigor O, Centers A, Jennes L.Distribution of ionotropic glutamate receptor subunit mRNAs in the rat hypothalamus[J].J Comp Neurol, 2001, 434(1):101-124.
[14] Petralia RS, Yokotani N, Wenthold RJ.Light and electron microscope distribution of the NMDA receptor subunit NMDAR1 in the rat nervous system using a selective anti-peptide antibody[J].J Neurosci, 1994, 14(2):667-696.
[15] Li DP, Byan HS, Pan HL.Switch to glutamate receptor 2-lacking AMPA receptors increases neuronal excitability in hypothalamus and sympathetic drive in hypertension[J].J Neurosci, 2012, 32(1):372-380.
[16] Marques-Lopes J, Van Kempen T, Waters EM, et al.Slow-pressor angiotensin II hypertension and concomitant dendritic NMDA receptor trafficking in estrogen receptor beta–containing neurons of the mouse hypothalamic paraventricular nucleus are sex and age dependent[J].J Comp Neurol, 2014, 522(13):3075-3090.
[17] Coleman CG, Wang G, Faraco G, et al.Membrane trafficking of NADPH oxidase p47(phox) in paraventricular hypothalamic neurons parallels local free radical production in angiotensin II slow-pressor hypertension[J].J Neurosci, 2013, 33(10):4308-4316.
[18] Garthwaite J.Concepts of neural nitric oxide-mediated transmission[J].Eur J Neurosci, 2008, 27(11):2783-2802.
[19] Wang G, Coleman CG, Chan J, et al.Angiotensin II slow-pressor hypertension enhances NMDA currents and NOX2-dependent superoxide production in hypothalamic paraventricular neurons[J].Am J Physiol Regul Integr Comp Physiol, 2013, 304(12):R1096-1106.
[20] 李霞, 李良, 樊明欣, 等.应激性血压升高对大鼠下丘脑肾上腺髓质素水平的影响[J].中国动脉硬化杂志, 2009, 17(5):354-358.
[21] Romero JC, Reckelhoff JF.State-of-the-Art lecture.Role of angiotensin and oxidative stress in essential hypertension[J].Hypertension, 1999, 34(4 Pt 2):943-949.
[22] Young CN, Cao X, Guruju MR, et al.ER stress in the brain subfornical organ mediates angiotensin-dependent hypertension[J].J Clin Invest, 2012, 122(11):3960-3964.
[23] 藏好晶.经下丘脑室旁核给予NF-κB抑制剂PDTC对高血压大鼠血压的影响及其机制的研究[D].太原:山西医科大学, 2013.
[24] Cato MJ, Toney GM.Angiotensin II excites paraventricular nucleus neurons that innervate the rostral ventrolateral medulla:an in vitro patch-clamp study in brain slices[J].J Neurophysiol, 2005, 93(1):403-413.
[25] Larson RA, Gui L, Huber MJ, et al.Sympathoexcitation in ANG II-salt hypertension involves reduced SK channel function in the hypothalamic paraventricular nucleus[J].Am J Physiol Heart Circ Physiol, 2015, 308(12):H1547-1551.
[26] Latchford KJ, Ferguson AV.Angiotensin depolarizes parvocellular neurons in paraventricular nucleus through modulation of putative nonselective cationic and potassium conductances[J].Am J Physiol Regul Integr Comp Physiol, 2005, 289(1):R52-58.
[27] Egli M, Berger T, Imboden H.Angiotensin II influences the hyperpolarization-activated current Ih in neurones of the rat paraventricular nucleus[J].Neurosci Lett, 2002, 330(1):53-56.
[28] Latchford KJ, Ferguson AV.Angiotensin II activates a nitric-oxide-driven inhibitory feedback in the rat paraventricular nucleus[J].J Neurophysiol, 2003, 89(3):1238-1244.
[29] Antunes VR, Yao ST, Pickering AE, et al.A spinal vasopressinergic mechanism mediates hyperosmolality‐induced sympathoexcitation[J].J Physiol, 2006, 576(Pt 2):569-583.
[30] Stocker SD, Keith KJ, Toney GM.Acute inhibition of the hypothalamic paraventricular nucleus decreases renal sympathetic nerve activity and arterial blood pressure in water-deprived rats[J].Am J Physiol Regul Integr Comp Physiol, 2004, 286(4):R719-725.
[31] Ferguson AV, Latchford KJ, Samson WK.The paraventricular nucleus of the hypothalamus–a potential target for integrative treatment of autonomic dysfunction[J].Expert Opin Ther Targets, 2008, 12(6):717-727.
[32] Leow-Dyke S, Allen C, Denes A, et al.Neuronal Toll-like receptor 4 signaling induces brain endothelial activation and neutrophil transmigration in vitro[J].J Neuroinflammation, 2012, 9:230.
[33] Medzhitov R, Preston-Hurlburt P, Janeway CA. Jr A human homologue of the Drosophila Toll protein signals activation of adaptive immunity[J].Nature, 1997, 388(6640):394-397.
[34] Rock FL, Hardiman G, Timans JC, et al.A family of human receptors structurally related to Drosophila Toll[J].Proc Natl Acad Sci USA, 1998, 95(2):588-593.
[35] Piccinini AM, Midwood KS.DAM Pening inflammation by modulating TLR signalling[J].Mediators Inflamm, 2010(10):1-21.
[36] Cardinale JP, Sriramula S, Mariappan N, et al.Angiotensin II-induced hypertension is modulated by nuclear factor-kappaBin the paraventricular nucleus[J].Hypertension, 2012, 59(1):113-121.
[37] Shi Z, Gan XB, Fan ZD, et al.Inflammatory cytokines in paraventricular nucleus modulate sympathetic activity and cardiac sympathetic afferent reflex in rats[J].Acta Physiol (Oxf), 2011, 203(2):289-297.
[38] Agarwal D, Elks CM, Reed SD, et al.Chronic exercise preserves renal structure and hemodynamics in spontaneously hypertensive rats[J].Antioxid Redox Signal, 2012, 16(2):139-152.
[39] Huang EJ, Reichardt LF.Neurotrophins:roles in neuronal development and function[J].Annu Rev Neurosci, 2001, 24:677-736.
[40] Poo MM.Neurotrophins as synaptic modulators[J].Nat Rev Neurosci, 2001, 2(1):24-32.
[41] Amaral MD, Pozzo-Miller L.BDNF induces calcium elevations associated with IBDNF, a nonselective cationic current mediated by TRPC channels[J].J Neurophysiol, 2007, 98(4):2476-2482.
[42] Jeanneteau FD, Lambert WM, Ismaili N, et al.BDNF and glucocorticoids regulate corticotrophin-releasing hormone (CRH) homeostasis in the hypothalamus[J].Proc Natl Acad Sci USA, 2012, 109(4):1305-1310.
[43] Lebrun B, Bariohay B, Moyse E, et al.Brain-derived neurotrophic factor (BDNF) and food intake regulation:a minireview[J].Auton Neurosci, 2006(126-127):30-38.
[44] Rosas-Vargas H, Martinez-Ezquerro JD, Bienvenu T.Brain-derived neurotrophic factor, food intake regulation, and obesity[J].Arch Med Res, 2011, 42(6):482-494.
[45] Toriya M, Maekawa F, Maejima Y, et al.Long-term infusion of brain-derived neurotrophic factor reduces food intake and body weight via a corticotrophin-releasing hormone pathway in the paraventricular nucleus of the hypothalamus[J].J Neuroendocrinol, 2010, 22(9):987-995.
[46] Hammack SE, Cheung J, Rhodes KM, et al.Chronic stress increases pituitary adenylate cyclase-activating peptide (PACAP) and brain-derived neurotrophic factor (BDNF) mRNA expression in the bed nucleus of the stria terminalis (BNST):roles for PACAP in anxiety-like behavior[J].Psychoneuroendocrinology, 2009, 34(6):833-843.
[47] Aliaga E, Arancibia S, Givalois L, et al.Osmotic stress increases brain-derived neurotrophic factor messenger RNA expression in the hypothalamic supraoptic nucleus with differential regulation of its transcripts relation to arginine-vasopressin content[J].Neuroscience, 2002, 112(4):841-850.
[48] Meredith GE, Callen S, Scheuer DA.Brain-derived neurotrophic factor expression is increased in the rat amygdala, piriform cortex and hypothalamus following repeated amphetamine administration[J].Brain Res, 2002, 949(1-2):218-227.
[49] 姬彩硕.针刺对自发性高血压大鼠下丘脑室旁核炎症因子含量及TLR4表达水平的影响[C]//世界针灸学术大会暨2017中国针灸学会年会论文集.中国针灸学会,2017:2.