电针对慢性内脏痛觉敏感大鼠延髓头端腹内侧核c-fos蛋白和NR1受体表达的影响
전침대만성내장통각민감대서연수두단복내측핵c-fos단백화NR1수체표체적영향
Effects of electroacupuncture on expression of c-fos protein and N-methyl-D-aspartate receptor 1 in the rostral ventromedia medulla of rats with chronic visceral hyperalgesia
  • 万方数据
    中西医结合学报 중서의결합학보
    JOURNAL OF CHINESE INTEGRATIVE MDEICINE
    2012年 4期 416-423 ,共8页

    祁德波%李为民

    기덕파%리위민

    受体,N-甲基-D-天冬氨酸%痛觉过敏%针刺疗法%c-fos蛋白%肠易激综合征%大鼠 受體,N-甲基-D-天鼕氨痠%痛覺過敏%針刺療法%c-fos蛋白%腸易激綜閤徵%大鼠
    수체,N-갑기-D-천동안산%통각과민%침자요법%c-fos단백%장역격종합정%대서
    receptors,N-methyl-D-aspartate%hyperalgesia%acupuncture therapy%protooncogene protein c-fos%irritable bowel syndrome%rats
    目的:针刺治疗对肠易激综合征(irritable bowel syndrome,IBS)患者的慢性腹痛具有良好疗效,然而,其神经生物学机制仍不清楚.本研究在电针(electroacupuncture,EA)缓解IBS模型大鼠慢性内脏痛觉敏感的基础上,观察和分析IBS大鼠延髓头端腹内侧核(rostral ventromedia medulla,RVM)中内脏反应神经元的兴奋性在针刺治疗前后的改变,以及RVM中N-甲基-D-门冬氨酸1型受体(N-methyl-D-aspartate receptor 1,NRl)在针刺缓解IBS模型大鼠慢性内脏痛敏中的参与机制.方法:采用新生9d的Sprague-Dawley雄性幼鼠,通过结直肠机械扩张刺激制作IBS慢性内脏痛觉敏感模型,持续两周.饲养6～8周后,观察大鼠由结直肠扩张(colorectal distention,CRD)诱发的痛阈压力值(pain threshold pressure,PTP)和腹部撤回反射(abdominal withdrawal reflex,AWR)评分变化.电针组穴位取双侧“足三里”和“上巨虚”,连续隔日治疗4次,假电针组不通电,其余与电针组相同.治疗结束后,取材并用免疫组织化学方法观察各组大鼠RVM中c-fos蛋白和NR1受体的表达变化.结果:与正常大鼠相比,成年IBS模型大鼠PTP值明显降低,且AWR评分明显升高(P＜0.01)；与电针治疗前相比,IBS大鼠电针治疗后PTP值明显升高(P＜0.01),AWR评分明显降低(P＜0.05)；与正常大鼠相比,IBS模型大鼠RVM各个亚核包括中缝大核(nucleus raphe magnus,NRM)、网状巨细胞核α部(nucleus reticularis gigantocellularis pars alpha,GiA)、外侧旁巨细胞核(nucleus lateralis paragigantocellulari,LPGi)以及网状巨细胞旁核(nucleus reticularis gigantocellularis,Gi)中c-fos蛋白和NR1受体阳性神经元的计数明显升高(P＜0.05),而电针治疗后Gi、LPGi、GiA中c-fos蛋白,以及Gi、LPGi、GiA、NRM中NR1受体免疫阳性神经元的计数与接受电针治疗前相比明显下降(P＜0.05)；假电针对PTP、AWR、c-fos蛋白和NR1受体阳性神经元的计数没有影响.结论:电针可以明显抑制IBS模型大鼠RVM中内脏反应神经元兴奋性异常增高,同时电针能明显抑制IBS模型大鼠RVM中NR1受体表达,这可能是RVM中内脏反应神经元异常增高的兴奋性下降的重要原因,同时也是针刺缓解慢性内脏痛觉敏感的机制之一.
    목적:침자치료대장역격종합정(irritable bowel syndrome,IBS)환자적만성복통구유량호료효,연이,기신경생물학궤제잉불청초.본연구재전침(electroacupuncture,EA)완해IBS모형대서만성내장통각민감적기출상,관찰화분석IBS대서연수두단복내측핵(rostral ventromedia medulla,RVM)중내장반응신경원적흥강성재침자치료전후적개변,이급RVM중N-갑기-D-문동안산1형수체(N-methyl-D-aspartate receptor 1,NRl)재침자완해IBS모형대서만성내장통민중적삼여궤제.방법:채용신생9d적Sprague-Dawley웅성유서,통과결직장궤계확장자격제작IBS만성내장통각민감모형,지속량주.사양6～8주후,관찰대서유결직장확장(colorectal distention,CRD)유발적통역압력치(pain threshold pressure,PTP)화복부철회반사(abdominal withdrawal reflex,AWR)평분변화.전침조혈위취쌍측“족삼리”화“상거허”,련속격일치료4차,가전침조불통전,기여여전침조상동.치료결속후,취재병용면역조직화학방법관찰각조대서RVM중c-fos단백화NR1수체적표체변화.결과:여정상대서상비,성년IBS모형대서PTP치명현강저,차AWR평분명현승고(P＜0.01)；여전침치료전상비,IBS대서전침치료후PTP치명현승고(P＜0.01),AWR평분명현강저(P＜0.05)；여정상대서상비,IBS모형대서RVM각개아핵포괄중봉대핵(nucleus raphe magnus,NRM)、망상거세포핵α부(nucleus reticularis gigantocellularis pars alpha,GiA)、외측방거세포핵(nucleus lateralis paragigantocellulari,LPGi)이급망상거세포방핵(nucleus reticularis gigantocellularis,Gi)중c-fos단백화NR1수체양성신경원적계수명현승고(P＜0.05),이전침치료후Gi、LPGi、GiA중c-fos단백,이급Gi、LPGi、GiA、NRM중NR1수체면역양성신경원적계수여접수전침치료전상비명현하강(P＜0.05)；가전침대PTP、AWR、c-fos단백화NR1수체양성신경원적계수몰유영향.결론:전침가이명현억제IBS모형대서RVM중내장반응신경원흥강성이상증고,동시전침능명현억제IBS모형대서RVM중NR1수체표체,저가능시RVM중내장반응신경원이상증고적흥강성하강적중요원인,동시야시침자완해만성내장통각민감적궤제지일.
    OBJECTIVE:Acupuncture has been clinically proved to be effective in treating abdominal pain in patients with irritable bowel syndrome ( IBS).However,its neurobiological mechanism remains largely unexplored.The aim of this study was to investigate the effect of electroacupuncture (EA) in relieving chronic visceral hyperalgesia and the possible involvement of N-methyi-D-aspartate receptor 1 (NR1) in rostral ventromedia medulla (RVM) of the brain in an IBS rat model.METHODS:To establish the IBS rat model,male Sprague-Dawley neonatal rats received colon mechanical irritation on a daily basis from the 9th to the 22nd day after their birth.After a resting period of another two to four weeks,behavioral tests of pain threshold pressure (PTP)and abdominal withdrawal reflex (AWR) responding to colorectal distention (CRD) stimuli were conducted to judge the colorectal sensitive situation.Then administration of EA at acupoints of Zusanli (ST36) and Shangjuxu (ST37) bilaterally in the hind limbs was repeated four times every other day,while sham-EA was done by inserting needles at similar acupoints without electrical stimulation.Immunohistochemical method was used to display the expression of protooncogene protein c-fos and NR1 in RVM of rats.RESULTS:The results demonstrated that the PTP values and AWR scores,in response to the CRD stimuli,significantly decreased and increased,respectively (P＜0.01,P＜0.01),while the number of immunoreactive neurons of c-fos protein and NR1 significantly increased in nucleus reticularis gigantocellularis (Gi),nucleus lateralis paragigantocellulari (LPGi),nucleus reticularis gigantocellularis pars alpha (GiA) and nucleus raphe magnus (NRM) of RVM in IBS model rats compared with the normal rats (P＜0.05).After EA treatment,PTP values and AWR scores significantly increased and decreased,respectively (P＜0.01,P＜0.05) ; the number of immunoreactive neurons of c-fos and NR1 significantly decreased respectively in Gi,LPGi and GiA and in Gi,LPGi,GiA and NRM (P＜0.05).No such effects on PTP values,AWR scores and the number of immunoreactive neurons of c-fos and IR1 were observed after sham-EA treatment.CONCLUSION:These data provide the evidence that EA can relieve chronic visceral hyperalgesia in rats with IBS,and such an effect may be correlated with inhibitory modulation of hyperactivity of neurons by means of down-regulating the high expression of NR1 in RVM of IBS model rats.
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