大鼠延髓内脏带及脊髓中神经元和胶质细胞对腹腔注射乙酸致内脏痛的反应及其相互关系的形态学研究
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摘要
有关疼痛机制研究一直都是神经科学研究的一个热点。内脏痛与躯体痛既有相似之处,也有不同区别点。内脏痛的性质模糊,定位不明确,机体的反应强烈,可引起出汗、心悸气短。目前有关内脏疼痛信息传递的内在机制仍不明确,以至在临床治疗上一直是个难题。
     目的:观察躯体痛刺激(针刺足三里穴)干预前后,腹腔注射乙酸致内脏痛模型大鼠中枢神经系统(延髓内脏带及脊髓)中神经元和胶质细胞(主要是星形胶质细胞和小胶质细胞)在光、电镜下的形态学反应,以探讨神经元和胶质细胞在针刺镇痛和内脏痛觉信息传递中的作用及其相互关系,为临床治疗内脏痛提供理论依据。
     方法:通过计算内脏痛行为学积分观察针刺足三里穴干预前后腹腔注射乙酸致内脏痛模型大鼠的行为学变化;采用免疫组织化学技术观察延髓内脏带及脊髓后角中即可早期基因Fos、胶质原纤维酸性蛋白(Glial Fibrillary Acidic Protein,GFAP)和OX42的表达变化、分布和相互关系;采用免疫组织化学方法,观察椎管鞘内注射P2X_4、P2X_7受体激动剂和拮抗剂干预前后内
The study of pain mechanism is always the interested point in neuroscience research. There is similar and different characteristic between visceral and somatic pain. In visceral pain, its quality is obscure, its accurate position in body is unclear, the response of body is greatly intense, such as sudation, tachycardia, breathe hard et al. Effective therapy for visceral pain is lacking, and the underlying mechanisms about the visceral noxious signal transmitting in the brain are poorly understood.
    Objective To study the function and relationship of neurons and glial cells in visceral noxious signal transmission and electroacupuncture analgesic effects in visceral pain(VP) model rats induced by intraperitoneal(i.p.) injection of 0.6% acetic acid(AA), by using single or double immunohistochemical methods and immunoelectron microscopy, we investigated the morphological response and relationship of neurons and glial cells in medullary visceral zone(MVZ) and spinal cord.
引文
1、史娟,庞志平,吕岩,李继硕。内脏痛的研究进展。神经解剖学杂志,1999:15(1):89-98。
    2、Xu Zhen, Wang Bai-Ren, Ding Yu-qiang, Kuang Fang, Wang Xi, Duan Xiao-Li,Jiao Xi-Ying, Ju Gong。Extracellular signal-regulated kinases 1/2 in neurons of the dorsal motor nucleus of the vagus nerve and nucleus of the solitary tract are activated by noxious visceral stimulus in mice.Neuroscience Letters 334 (2002) 103-106.
    3、易春霞,茹立强,胡道松。迷走神经参与胃伤害性信息向下丘脑的传递。中国神经科学杂志,2004:20(5):353-356。
    4、Rao ZR, Ju G. Morphology of medullary visceral zone. Chin Sci Bull, 1999; 44(1): 1-10.
    5、Li T,Gao W,Rao ZR. Noxious somatic stimulation-indused expression of Fos-like immunoreactivity in catecholaminergic neurons with habenular nucleus projection in the medullary visceral zone of rat.Brain Res,1998;783:51.
    6、韩志安,饶志仁,晋光荣,施际武。大鼠“延髓内脏带”向终纹床核役射的儿茶酚胺能神经元对内脏伤害性刺激的Fos表达。神经解剖学杂志,1996;12(1):51-56。
    7、陈良为,饶志仁,施际武。大鼠延髓内脏带的化学神经解剖学。解剖学报,1996:27(4):386-390。
    8、陈良为,晋光荣,饶志仁,施际武。大鼠胃肠道伤害性刺激引起的中枢神经系统c-fos表达。神经解剖学杂志,1993:9(2):185—191。9、Chen LW,Rao ZR, Shi JW.Catecholaminergic neurons in the nucleus tractus solitarii which send their axons to the periaqueductal gray express Fos protein after noxious stimulation of the stomach: a triple labeling study in the rat. Neuroscience Letters. 1995; 189:179-181.
    10、陈良为,饶志仁,施际武。大鼠“延髓内脏带”向杏仁核投射的儿茶酚胺神经元对内脏伤害性刺激的Fos表达。神经解剖学杂志,1994:10(2):139—144。
    11、董元祥,熊抗辉,饶志仁,施际武。大鼠延髓至下丘脑室旁核的儿茶酚胺神经元在胃伤害性刺激后的Fos表达。解剖学报,1996:27(1):20—25。
    12、L.W. Chen, Z. R. Rao, J. W. Shi. Catecholaminergic neurons in the nucleus tractus solitarii which send their axons to the midbrain periaqueductal gray express Fos protein after noxious stimulation of the stomach a triple labeling study in the rat Neurosci Lett. 1995; 189 (2): 179-181
    13、G. R. Jin, Z. R. Rao, J. W. Shi. Visceral noxious stimulation iduced expression of Fos protein in medullary catecholaminergic neurons pronecting to nucleus accumbens in the rat: a study with triple labeling method of HRP tracing combined with Fos and TH immunohistochemistry. Brain Res. 1994;648 (2): 196-202
    14、韩志安,饶志仁,晋光荣,施际武.大鼠“延髓内脏带”向终纹床核役射的儿茶酚胺能神经元对内脏伤害性刺激的Fos表达。神经解剖学杂志,1996;12(1):51-56
    15、H.G. Jia, Z. R. Rao, J. W. Shi. Evidence of GABAergic control??over the catecholaminergic projection from the medulla oblongata to the central nucleus of the amygdala. J Comp Neurol., 1997;381(3): 262-281.
    16、Z. J. Wang, Z. R. Rao, J. W. Shi, Tyrosine bydroxylase, neurotensin or cbolecystokinin-containing neurons in the nucleus tractus solitarii send projection fibers to the nucleus accumbens in the rat Brain Res. 1992;578 (4): 347-350.
    17、Y.Q. Li, Z. R. Rao, J. W. Shi. Substance B-like immunoreactive neurons in the nucleus tractus solitarii of the rat send their axons to the nucleus accumbens Neurosci Lett. 1990;120 (2): 194-196.
    18、陈良为,饶志仁,施际武,等.内脏伤害性刺激诱导的大鼠延髓内Fos表达。解剖学报,1995;26(2):127-131.
    19、王颖,邱建勇,段丽,陈良为,饶志仁。胃伤害性刺激诱导大鼠脑干星形胶质细胞蛋白表达及其与神经元的关系。中国组织化学与细胞化学杂志,2001;10(2):219—223。
    20、贾宏阁,饶志仁,施际武.大鼠孤束核迷走复合体儿茶酚胺能神经元向杏仁核的直接投射—HRP与免疫组织化学双标记研究。神经解剖学杂志,1992;8(2):233-237
    21、贾宏阁,饶志仁,施际武.大鼠臂旁核内接受孤束核内脏传入之神经元同时接受中央杏仁核的反馈调节——溃变、HRP法结合包埋后免疫电镜研究。神经解剖学杂志,1994;10(4):294-298。
    22、H.G. Jia, Z. R. Rao, J. W. Shi. An indirect projection from the nucleus of the solitary tract to the central nucleus of the amygdala via the parabrachlal nucleus in the rat: a light and electron microscopic study. Brain Res. 1994;663:181-190.23、董元祥,熊抗辉,饶志仁,施际武.大鼠延髓至下丘脑室旁核的儿茶酚胺能投射神经元在胃伤害性刺激后的Fos表达。解剖学报,1996:27(1):20-25。
    24、董元祥,熊抗辉,饶志仁.大鼠延髓至下丘脑腹内侧核的儿茶酚胺能投射神经元在胃伤害性刺激后的Fos表达。中国组织化学与细胞化学杂志,1995;4(3):229-235。
    25、董元祥,熊抗辉,饶志仁.大孤束核和延髓腹外侧区至下丘脑外侧区的儿茶酚胺能投射神经元在胃伤害性刺激后的Fos表达。神经解剖学杂志,1995;11(4):363-368。
    26、陈京红,滕国玺。内脏痛的中枢感觉及传导机制。解剖科学进展,1998:4(2):119-126。
    27、张建梁,张宏启。内脏痛的脊髓通路研究进展。国外医学·生理、病理科学与临床分册。2005;25(3):211-214。
    28、Deleo JA, Coombs DW, McCarthy LE. Differential c-fos-like protein expression in mechanically versus chemically induced visceral nociception. Brain Res Mol Brain Res, 1991,11 (2): 167-170.
    29、Nakagawa T, Katsuya A, Tanimoto S, Yamamoto J, Yamauchi Y, Minami M, Satoh M, Differential patterns of c-fos mRNA expression in the amygdaloid nuclei induced by chemical somatic and visceral noxious stimuli in rats.Neuroscience Letters, 2003; 344:197-200.
    30、Sinniger V, Porcher C, Mouchet P, Juhem A, Bonaz B, c-fos and CRF receptor gene transcription in the brain of acetic acid-induced somato-visceral pain in rats, Pain, 2004;110: 738-750.
    31、董元祥,武胜昔,吕葆真,李云庆。胃伤害性刺激对大鼠下??丘脑乳头体前区内SP mRNA阳性神经元的影响。第四军医大学学报,2000;21(12):1431-1435。
    32、Watkins L.R., Martin D., Ulrich P., Tracey K.J., Maier S.F., Evidence for the involvement of spinal cord glia in subcutaneous formalin induced hyperalgesia in the rat. Pain, 1997;71:225-235.
    33、Watkins L.R., Milligan E.D., Maier S.F., Glial activation: a driving force for pathological pain. Trends Neurosci. 2001a.;24:450-455.(a)
    34、Watkins L.R., Milligan E.D., Maier S.F.,. Spinal cord glia: new players in pain. Pain. 2001b; 93:201-205. (b)
    35、Tsuda M., Shigemoto-Mogami Y., Koizumi S., Mizokoshi K., Kohsaka S., Michael W. Salter M.W. & Inoue K., P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury. Nature, 2003;424, 778-783.
    36、Fu K.Y., Light A.R., Matsushima G.K., Maixner W. Microglial reactions after subcutaneous formalin injection into the rat hind paw. Brain Res. 1999;825:59-67.
    37、Milligan E.D., Mehmert K.K., Hinde J.L., Harvey L.O., Martin D., Tracey K.J., Maier S.F., Watkins L.R., Thermal hyperalgesia and mechanical allodynia produced by intrathecal administration of the human immunodeficiency virus-1 (HIVS1) envelope glycoprotein, gp120. Brain Res. 2000;861:105-116.
    38、袁华、段丽、邱勇、高立志、张萍、曹荣、饶志仁。大鼠侧脑室注射甘珀酸后下丘脑视上核星形细胞和神经元对高渗刺激反??应的影响。解剖学报,2004;35(2):127-131。
    39、Li Duan, Hua Yuan, Chang-Jun Su, Zhi-Ren Rao. Ultrastructure of junction areas between neurons and astocytes in rat supraoptic nuclei. World J Gastroenterol 2004; 10(1): 117-121.
    40、刘利兵,陆松鹤,张英梅,陈健康,黄裕新。神经在电针刺大鼠足三里对胃机能影响中的作用及其与经络的联系。河北医学,2002;8(5):385-387。
    41、荣培晶,朱兵,黄启福,高昕妍,贲卉,李艳华。针刺抑制直结肠伤害性扩张引起的大鼠脊髓背角神经元反应。中国针灸,2005;25(9):645-650。
    42、金善学,赵华,秦秉志,等。内脏和躯体初级传入冲动在猫骶髓后连合核的汇聚。神经解剖学杂志,1997;13(1):291。
    43、Jian-Hua Liu, Jiangshan Li, Jie Yan, Xiao-Rong Chang, Ren-Fa Cui, Jun-Feng He, Ji-Ming Hu. Expression of cofos in the nucleus of the solitary tract following electroacupuncture at facial acupoints and gastric distension in rats. Neuroscience Letters, 2004;366:215-219.
    44、Jian-Hua Liu, Jie Yan, Shou-Xiang Yi, Xiao-Rong Chang, Ya-Ping Lin, Ji-Ming Hu, Effects of electroacupuncture on gastric myoelectric activity and substance P in the dorsal vagal complex of rats.Neuroscience Letters, 2004;356: 99-102.
    45、刘健华,李江山,严洁,易受乡,林亚平,常小容。针刺“足三里”对大鼠孤束核P物质的影响。针刺研究,2003:28(1):5-9。
    46、Cheng Huang, Hua Long, Yu-Shun Shi, Ji-Sheng Han, You Wan, Ketamine enhances the efficacy to and delays the development??of tolerance to electroacupuncture-induced antinociception in rats.Neuroscience Letters, 2005;375:138-142.
    47、Yu-Qiu Zhang, Guang-Chen Ji, Gen-Cheng Wu, Zhi-Qi Zhao Excitatory amino acid receptor antagonists and electroacupuncture synergetically inhibit carrageenan-induced behavioral hyperalgesia and spinal fos expression in rats.Pain, 2002;99:525-535.
    48、朱丽霞,叶燕燕,莫孝荣,吉长福。脑内GABA参与针刺镇痛的受体机制。针刺研究,2001:26(3):200-202。
    49、杨芝兰,张玉秋,吴根诚。孤啡肽对痛觉调制和针刺镇痛作用的研究进展。国外医学·生理、病理科学与临床分册,2001;21(4):312-314。
    50、刘玲爱,宋朝佑,王静明,由振东,余静,王成海,林葆城。电针大鼠“足三里”时脑内12个核团生长抑素含量的变化。中国疼痛医学杂志,1998:4(2):102-105。
    51、杨智杰,唐敬师,袁斌,贾红。丘脑中央下核和腹外侧眶皮层在针刺镇痛和痛觉调制中的整合作用。针刺研究,2001;26(3):196-198。
    52、刘俊岭,陈振荣,胡翔龙,荣培晶。2000年度经络研究进展。针刺研究,2001:26(1):72-76。
    53、尹岭,金香兰,石现,等。针刺足三里穴PET和fMRI脑功能成像的初步探讨。中国康复理论与实践,2002;8(9):523-524。
    54、武晓冬,王佩。针刺镇痛机理研究概述。中国中医基础医学杂志,1999;5(12):59-62。
    55、胡格吉乐图,周茂林,欧阳五庆,陈树林,针灸作用的初级传入途径及意义。针刺研究,2000;25(3):236-240。56、Galligan JJ, Bertrand PP. ATP mediates fast synaptic potentials in enteric neurons. J Neurosci, 1994; 14(12):7563-7571.
    57、Vulchanova L, Reidi MS,Shuster SJ, et al. P_(2X3) is expressed by DRG neurons that terminate in innerlamine II. Eur J Neurosci,1998; 10:3470-3478.
    58、Li J, Perl ER. ATP modulation of synaptic transmission in the spinal substantia gelatinosa, et al. Neurosci,1995; 15:3357-3365.
    59、Gu JG, MacDermott AB. Activation of ATP P2X receptors elicits glutamate release from sensory neuron synapses. Nature. 1997;389(6652):749-753.
    60、Guthrie PB, Knappenberger J, Segal M, Bennett M.V, Charles A.C, and Kater S.B. ATP mediates glial calcium wave propagation. J. Neurosci,1995; 19:520-528.
    61、Cotrina M.L, Lin J.H, Alves-Rodrigues A, Liu S, Li J, Azmi-Ghadimi H, Kang J, Naus C.C, and Nedergaard M. Connexins regulate calcium sigaling by controlling ATP release. Proc. Acad. Sci. USA.1998;95:15735-15740.
    62、Cotrina M.L, Lin J.H, Lopez-Garcia J.C, Naus C.C, and Nedergaard M. ATP-mediated glia signaling. J. Neurosci,2000;20:2835-2844.
    63、Zhang JM, Wang HK, YE CQ, Ge WP, Chen YR, Jiang ZL, Wu CP, Po MM, Duan SM. ATP released by astrocytes mediates glutamatergic activity-dependent heterosynaptic suppression. Neuron.2003;40:971-982.
    64、Coll J.A.M., Beggs S, Boudreau D, Boivin D, Tsuda M, Inoue K,Gravel C, Salter M.W, Koninck Y.D. BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature,2005;438:1017-1021.
    65、Antonio G.D, Quattrini A, Cin ED, Fulgenzi A, Ferrero ME. Antinociceptive effect of a new P_(2z)/P_(2X7) antagonist, Oxidized ATP, in arthritic rats. Neuroscience Letters. 2002; 327:87-90.
    66、Burnstock G. Purine-mediated signaling in pain and visceral perception. Trends Pharmacol Sci,2001;22 (4):182-188.
    67、Zimmermann M.,. Ethical guidelines for investigations of experimental pain in conscious animals. Pain,1983;16: 109-110.
    68、Schmauss C,Yaksh TL. In vivo studies on spinal opiate receptor systems mediating antinociception. Ⅱ. Pharmacological profiles suggesting a differential association of mu,delta and kappa receptors with visceral chemical and cutaneous thermal stimuli in the rats. pharmacol Ther, 1984,28:1-12.
    69、王泳涛,吕国蔚。福尔马林引起的急性内脏炎症痛模型。中国应用生理学杂志,1999;15(4):372-376。
    70、张遐,鞠躬。c-Fos癌基因的诱导和显示—一种反映神经功能通路的新方法。生理科学进展,1991;22(4):299-305。
    71、张辉,段丽,饶志仁。大鼠脑干星形胶质细胞和神经元对一侧胫、腓骨骨折后的即刻应激反应及其相互关系。第四军医大学学报,2002;23(5):415-418。
    72、闫丽萍,马骋,项晓人,何崇,王玲玲。电针抑制内脏痛诱发的大鼠丘脑背内侧核痛放电。中国疼痛医学杂志,2004;10(3):177-180。73、Del Arco A, Segovia G, Fuxe K, et al. Changes in dialysate concentrations of glutamate and GABA in the brain: an index of volume transmission mediated actions? Neurochem. 2003; 85(1): 23-33.
    74、Verkhratsky A, Kettenmann H. Calcium signaling in glial cells. Trends Neurosci, 1996; 19:346.
    75、张辉、段丽、张光运、李震、饶志仁。鞘内注射甘珀酸对大鼠热痛刺激反应的影响。中国神经科学杂志,2003;19(2):88-93。
    76、张辉、段丽、贾轶、刘莹莹、林英华、饶志仁。大鼠腰髓背角星形胶质细胞对外伤性痛疼刺激的反应及其与神经元的免疫电镜研究。神经解剖学杂志,2003;19(2):182-186。
    77、Gerlinda E Hermann.Induction of endogenous TNF-α: supperssion of centrally stimulated gastric motility.The American Physiological Society,1999:R59-68
    78、Emch GS,Hermann GE,Rogers RC.TNF-αactivates solitary nucleus neurons responsive to gastric distension.Am J Physiol, 2000; 279(3):G582-596.
    79、Guo L.H., Liang H. Guo., Traumann K., Katrin Trautmann, Schluesener H.J. Hermann J. Schluesener. Expression of P2X_4 receptor by lesional activated microglia during formalin-induced inflammatory pain. Neuroimmunol, 2005; 163:120-127.
    80、Soto, F., Garcia-Guzman, M., Gomez-Hemandez, J.M., Hollmann, M., Karschin, C., Stuhmer, W., P2X_4 : an ATP-activated ionotropic receptor cloned from rat brain. Proc. Natl. Acad. Sci. USA 1996a;93, 3684-3688.81、Le, K.-T., Villeneuve, P., Ramjaun, A.R., McPherson, P.S., Beaudet, A., Seguela, P., Sensory presynaptic and widespread somatodendritic immunolocalization of central ionotropic P2X ATP receptors. Neuroscience, 1998; 83: 177-190.
    82、Wittkowski, W., Brinkmann, H., 1974. Changes of extent of neurovascular contacts and number of neuro-glial synaptoid contacts in the pituitary posterior lobe of dehydrated rats. Anat Embryol (Berl).146, 157-165.
    83、Bergles, D.E., Roberts, J.D., Somogyi, P., Jahr, C.E., 2000.Glutamatergic synapses on oligodendrocyte precursor cells in the hippocampus. Nature. 405, 187-191.
    84、Araque, A., Parpura, V., Sanzgiri, R.P., Haydon, P.G., 1999. Tripartite synapses: glia, the unacknowledged partner. Trends Neurosci. 22, 208-215.
    85、Ventura, R., Harris, K.M., 1999.Three-dimensional relationships between hippocampal synapses and astrocytes. Neurosci. 19, 6897-6906.
    86、Nadarajah, B., Thomaidou, D., Evans, W.H., Parnavelas, J.C, 1996. Gap junctions in the adult cerebral cortex, regional differences in their distribution and cellular expression of connexins. Comp. Neurol. 376, 326-342.
    87、Holder JW, Elmore E, Barrett JC. Gap junction function and cancer. Cancer Res, 1993, 53: 3475-3485.

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