(翻译)灸法镇痛的外周机制.docx

一、 灸法镇痛的外周机制Peripheral mechanism of moxibustion analgesic近年来研究证实,内脏痛觉敏感是IBS重要的病理生理学基础之一,其发生机制非常复杂。以往病理机制研究多集中在胃肠道局部病变,如肠嗜铬细胞和肥大细胞的活化、肠壁内脑肠肽及其受体的表达异常等，在灸法对IBS内脏痛镇痛外周机制研究中，主要以外周细胞分子的研究为主，报道如下：The recent studies have proved that visceral hyperalgesia with its complex mechanism is one of the important pathophysiological basis of IBS. The previous studies focused pathological changes on local lesions in gastrointestinal tract, such as the activation of enterochromaffin cells and mast cell, intramural ghrelin and abnormal expression of its receptor, etc. Peripheral cellular and molecular are mainly used by studies on peripheral mechanism of IBS analgesic induced by moxibustion, reported as follows,肥大细胞与五羟色胺Mast cells and serotoninIBS患者末端回肠、升结肠及直肠MC的数目、浸润程度及脱颗粒明显高于健康者【4,5】。MC number, degree of infiltration and degranulation in terminal ileum, ascending colon and rectum of IBS patients were significantly higher than healthy individuals 4,5MC在应激后活性显著增强,通过释放大量的生物活性介质来影响肠道平滑肌运动、胃结肠反射等，从而引起肠动力异常、内脏痛等各种IBS症状。After stress, MC was significantly enhanced and released of a large number of biological activity media in order to influence intestinal smooth muscle, stomach colon reflection, and to cause intestinal motility disorders, visceral pains and other symptoms of IBS.IBS内脏痛大鼠的“天枢”穴区存在MC数量的增多，且具有明显的脱颗粒现象；温和灸能够通过少量下调穴区MC的数量，但能明显提高MC的脱颗粒率，来起到治疗IBS内脏痛的作用。并且MC的脱颗粒现象在一定范围内随艾灸温度的升高而更加明显【6】。MC in acupoit area of Tinsh（ST25） in rats of IBS visceral pain increased, and degranulation was found; warm moxibustion regulated down a small amount of MC number, but it significantly increased the rate of MC degranulation in order to treat the visceral pain of IBS. And MC degranulation of moxibustion was more obvious in certain range of temperature 6.在消化道中，由MC分泌的单胺类神经递质5-HT参与了多种生理调控之外，也参与了IBS患者肠动力反应过强、内脏痛、心理障碍或精神异常等病理机制【7,8】。In the digestive tract, 5-HT was volved in a variety of physiological regulations such as strong eaction, visceral pain, mental disorder or mental abnormalities in IBS patients. 7 , 8. IBS患者体内5-HT水平增加,一方面导致内脏传入神经及肠神经系统敏感性增高,激活多种神经活性物质,使参与脑-肠调节的化学信号异常,导致胃肠道动力改变、内分泌功能异常和内脏痛【9】。The increasing level of 5-HT in IBS patients, on the one hand, leads to visceral afferent and enteric nervous system hypersensitivity, activate a variety of neuroactive substances, abnormally regulates the brain - gut chemical signals, which causes gastrointestinal motility, endocrine dysfunction and visceral pain. 9另一方面5-HT的不同亚型作用于各种受体,引起IBS患者的肠道感知、运动和分泌功能的改变,从而产生腹痛、腹泻等各种症状【10】。On the other hand, 5-HT acts on a variety of different subtypes of receptors, which causes changes of intestinal IBS patients perception, movement and secretion, which results in abdominal pain, diarrhea and other symptoms 10.艾灸能够通过调节结肠的5-HT通路来实现降低IBS大鼠的内脏痛的程度【11,12】，同时艾灸可以显著降低D-IBS和C-IBS模型大鼠结肠组织中MC的数量【13】，从外周穴区与结肠组织都有MC参与介导，可以推断MC及其释放的5-HT介导了艾灸镇痛机制中的外周机制。Moxibustion regulates down the degree of visceral pain in IBS rats through 5-HT pathway 11,12, and moxibustion significantly reduces the number of MC in D-IBS and C-IBS rat colon tissue 13. According to the mediating of MC in peripheral acupoint area and colon tissue, the peripheral mechanisms of moxibustion analgesia is proved to be induced by MC and 5-HT.但是对于肥大细胞释放的其他介质如组胺、蛋白多糖、血小板活性因子、细胞因子、白三烯和前列腺素等是否参与灸法的IBS镇痛机制有待进一步实验研究证实。But further studies are needed to porve whether the release of other MC mediators such as histamine, proteoglycans, platelet activating factor, cytokines, leukotrienes and prostaglandins are involved in the mechanism of moxibustion analgesic in IBS.激动素原蛋白1Kinetin original protein 1PKs是伤害性感受致敏物质，在大鼠中枢或/和外周注入少量PKs/Bv8，可产生呈剂量依赖性的强烈痛觉过敏【14-17】。PKs are nociceptive allergenic substances. Injection of a small amount of PKs/Bv8,in the rat central and / or peripheral can cause a strong dose-dependent hyperalgesia 14-17.激动素原蛋白受体（Prokineticin Receptors,PKRs）表达于中枢和外周神经系统部分C纤维神经元和A有髓纤维神经元，Kinetin original receptor (Prokineticin Receptors, PKRs) is expressed in the central and peripheral nervous system part of the C fiber neurons and A myelinated fiber neurons .PKs通过初级敏感神经元和脊髓，使外周伤害性感受器对热刺激、化学刺激、机械刺激产生强烈的致敏作用，直接参与伤害性刺激所致的伤害感受阈变化与伤害性疼痛反应，介导初级和中枢疼痛致敏【18,19】Through primary sensitive neurons and spinal cord, a strong sensitization to heat stimuli, chemical stimulation and mechanical stimulation is produced by the peripheral nociceptors, and directly involved in nociception induced changes in nociceptive threshold and nociceptive responses to mediate the primary and central pain sensitization 18,19.PK1是新发现的内源性胃肠动力调节器，PK1及PKR1也可能通过参与IBS大鼠肠道动力调节，从而介导IBS内脏高敏感疼痛信号传递，PKR1基因敲除大鼠表现为Bv8介导的痛觉过敏受损、对热伤害反应减弱、对热和机械性高敏感性降低【19】，PK1 is a newly discovered endogenous regulator of gastrointestinal motility. PK1 and PKR1 may also be involved in intestinal motility regulation of IBS rat, which mediates visceral hypersensitivity IBS pain signals pass,.PKR1 knockout rats showed Bv8 referral mediated hyperalgesia damage, reduced response to thermal injury of high thermal and mechanical properties decreased sensitivity 19, PK1及PKR1与疼痛密切相关。PK1/PKR1参与IBS内脏高敏感疼痛信号传递。激动素原蛋白1及其受体可能通过结直肠刺激介导了新生大鼠的内脏高敏感性。温和灸可调节慢性内脏高敏感大鼠结肠PK1/PKR1的表达，这可能是温和灸缓解肠易激综合征内脏高敏感疼痛的作用机制之一【20】。其作用途径以及艾灸对其的干预机制有待于进一步实验研究。PK1 and PKR1 are closely related with pains. PK1/PKR1 visceral hypersensitivity in IBS pain signal transmission. Kinetin original protein 1 and its receptor may mediate neonatal rats with visceral hypersensitivity through the stimulation of colorectal. Warm moxibustion regulates PK1/PKR1 expression in chronic visceral hypersensitivity rats colon, which may be one of the mechanisms of warm moxibustion relieving pains of IBS visceral hypersensitivity 20. Its pathways and intervention mechanism needs to be proved.辣椒素受体(transientreceptorpotential vanilloidreceptor1,TRPV1) 辣椒素受体属于瞬时感受器电位离子通道(transient receptorpotential,TRP)超家族,TRP1在结肠无明显炎症的IBS患者的传入神经纤维表达上调【21】。Transient receptor potential vanilloid receptor belongs to ion channels (transient receptorpotential, TRP) superfamily. The expression of TRP1 in afferent nerve fibers is upregulated in in the colons of IBS patients with no significant inflammation21. Akbar等发现IBS患者直肠乙状结肠连接部的神经纤维TRPV1免疫阳性值是对照组的3.5倍,TRPV1表达显著与疼痛严重度相关。IBS内脏高敏感大鼠骨髓细胞中存在TRPV1的过度表达【23】。Akbar found that TRPV1 immunoreactive value of nerve fibers in rectosigmoid junction in IBS patients was 3.5 times of the control group. The expression of TRPV1 was significantly related with pain severity. The presence of over-expression of TRPV1 exists in bone marrow cells of IBS visceral hypersensitivity rat23.但未见关于TRPV2在IBS内脏痛方面的研究报道，但是TRPV2具有很强的机械敏感性【24】，在IBS内脏高敏感大鼠模型制备过程中，采用的直结肠刺激方法是一种机械性刺激，推测这种刺激可能会被TRPV2感知，从而参与IBS内脏高敏感的产生。IBS内脏痛大鼠TRPV2mRNA和蛋白表达上调，提示IBS内脏痛可能也存在TRPV2的高表达。 No research reported TRPV2 with visceral pain in IBS, though TRPV2 has a strong mechanical sensitivity 24. In the rat model of visceral hypersensitivity IBS, the direct method of mechanical stimulation in colon is used, which surmises that TRPV2 would participate in the generation of IBS visceral hypersensitivity. The unregulate