大鼠结肠慢性炎性刺激诱导腰骶髓和延髓Fos的表达及其意义

目的　探讨实验性大鼠结肠慢性炎性刺激诱导腰骶髓和延髓中Fos的表达及其意义。方法　成年雄性SD大鼠 ,实验组 (n =1 6 )予三硝基苯磺酸 (TNBS)灌肠诱导结肠炎 ,实验对照组 (n =8)予生理盐水灌肠 ,空白对照组 (n =2 )不予任何刺激 ;分别在灌肠后 3、7、1 4和 2 8d ,采用免疫组化法观察实验组大鼠腰骶髓和延髓中Fos阳性神经元的数量和分布 ,并与对照组进行比较。结果　TNBS灌肠诱导Fos表达多数分布在脊髓背角深层 (Ⅲ～Ⅳ和Ⅴ～Ⅵ层 )和由孤束核、腹外侧区及网状结构形成的延髓内脏带中。TNBS灌肠后 3d ,脊髓和延髓中Fos表达无明显增多。灌肠后 7和 1 4d ,脊髓和延髓中Fos表达明显多于实验对照组 (P <0 .0 5 )。灌肠后 2 8d ,延髓中Fos表达下降 ,与对照组无明显差异 ,部分大鼠脊髓中Fos阳性神经元数 (5 4 .1± 1 6 .3)仍明显多于对照组 (1 2 .2± 2 .6 ,P <0 .0 5 )。结论　脊髓Fos阳性神经元可能在结肠慢性炎性刺激引起的内脏高敏感性中起作用 ,而延髓可能不是内脏高敏感性形成的主要部位。     

胃扩张对大鼠脑、脊髓和肌间神经丛Fos蛋白和降钙素基因相关肽表达的影响

背景:功能性消化不良是一种常见疾病,越来越多的证据显示其发病与内脏神经敏感性增高有关。目的:通过测定大鼠伤害性胃扩张后脑、脊髓和肌间神经丛Fos蛋白和降钙素基因相关肽(CGRP)的表达,探索内脏刺激传入的途径和方式。方法:24只成年Sprague-Dawley雄性大鼠随机分为3组:实验组(12只)、手术对照组(6只)和空白对照组(6只)。实验组和手术对照组先植入胃内气囊。48h后,实验组接受反复的气囊扩张[80mmHg(1mmHg=0.133kPa)],2h后处死全部实验动物,立即取材。采用免疫组化法观察脑、脊髓和肌间神经丛Fos蛋白和CGRP的表达。结果:实验组杏仁核、延髓和胸髓Fos蛋白的表达较其他两组显著增强(P均<0.01),肌间神经丛的Fos蛋白表达3组间无显著差异。实验组延髓、胸髓CGRP表达较其他两组显著增强(P<0.05和P<0.01)。延髓和胸髓中Fos蛋白与CGRP的表达显著相关(rs分别为0.794和0.728,P均<0.01)。结论:胃扩张刺激可以兴奋皮层下中枢,CGRP在内脏刺激信号的传入过程中起重要作用。     

替加色罗对结肠炎诱导的大鼠腰骶髓Fos、P物质和降钙素基因相关肽表达的影响

背景:临床研究发现,替加色罗可以明显改善肠易激综合征患者的腹部不适和腹痛,但其调节内脏感觉的机制目前尚不清楚。目的:观察替加色罗对结肠炎诱导的大鼠腰骶髓Fos、P物质(SP)和降钙素基因相关肽(CGRP)表达的影响,探讨替加色罗降低内脏敏感性的作用途径。方法:成年雄性Sprague-Dawley大鼠24只,以三硝基苯磺酸灌肠诱导结肠炎并随机分为实验组1:替加色罗灌胃,每天2mg/kg;实验组2:替加色罗灌胃,每天1mg/kg;对照组:生理盐水灌胃,2.0ml/d。连续灌胃7天后,采用免疫组化方法检测大鼠腰骶髓Fos、SP和CGRP的表达。结果:结肠炎可诱导对照组大鼠腰骶髓(L5～S1)背角深层Fos表达以及背角浅层SP和CGRP表达。实验组1大鼠腰骶髓背角Fos阳性神经元数(22.0±7.7)和SP密度(12.5%±1.4%)显著低于对照组(62.2±18.9和35.9%±8.9%,P<0.05),CGRP密度(1.2%±1.1%)与对照组(2.8%±2.4%)相比无显著差异。实验组2大鼠腰骶髓背角Fos、SP和CGRP的表达与对照组相比均无显著差异。结论:替加色罗可以明显减少结肠炎诱导的大鼠腰骶髓背角Fos和SP的表达,其降低内脏敏感性的作用可能与抑制脊髓背角SP的表达有关。     

食管酸灌注对内脏高敏感模型大鼠中枢神经系统Fos表达的影响

目的观察在内脏高敏感状态下食管酸灌注对中枢神经系统（CNS）各部位Fos蛋白表达的影响,以初步明确CNS参与内脏高敏感性应答和调控的具体部位及中枢传导通路的变化.方法健康SD大鼠36只,随机分为5组.A组：正常对照组6只;B组：0.9%氯化钠溶液对照组7只;C组：食管酸灌注组8只;D组：卵清蛋白（OVA）致敏组7只;E组：OVA＋食管酸灌注组8只.采用腹腔注射鸡OVA基础致敏联合食管酸灌注的方法建立食管内脏高敏感性大鼠模型;采用免疫组化方法和显微图像分析等技术研究在生理条件、内脏高敏状态下食管酸灌注后CNS各部位的Fos蛋白激活模式的差异.结果鸡OVA致敏联合食管酸灌注组被激活了一个复杂而广泛大脑网络,其在额顶皮质、岛叶、扣带皮质、中央杏仁核、Kol-liker Fuse核、疑核、臂旁核、下丘脑室旁核、丘脑室旁核、三叉旁核、孤束核、最后区、延髓网状核等核团Fos样免疫活性（FLI）神经元的数目均显著高于其余各组（P＜0.05）,但在迷走神经背核、下丘脑视上核、中脑导水管周围灰质、腹外侧眶皮层的FLI神经元数量,与食管酸灌注组比较则无明显改变（P＞0.05）.且该组大鼠的中央杏仁核、臂旁核、室旁核、三叉旁核、孤束核的FLI阳性产物的平均吸光度（A）值亦较其余各组明显增高（P＜0.05）.结论腹腔注射鸡OVA基础致敏对食管酸灌注诱导的CNS内Fos蛋白表达有活化作用,提示内脏高敏感状态可导致CNS不同核团神经元功能发生不同程度的障碍,CNS整合、处理食管感觉传入信息功能异常.     

七氟醚对甲醛致痛诱导Fos蛋白在大鼠脊髓内表达的影响

15只SD大鼠,随机分为对照组、吗啡组、七氟醚组,各5只。七氟醚组吸入3%七氟醚5 min后腹腔注射生理盐水,右侧后肢跖部皮下注射4%甲醛150μl,继续吸入七氟醚;对照组、吗啡组腹腔分别注射生理盐水、10 mg/kg吗啡5 min后,右侧后肢跖部皮下注射甲醛。2 h后处死大鼠,取脊髓L3~L5节段,用免疫组化法观察脊髓内Fos蛋白的表达。结果:甲醛致痛仅诱导Fos在右侧脊髓表达,与对照组比较,吗啡组、七氟醚组脊髓各层Fos蛋白免疫反应阳性神经元(FLIN)数量显著降低(P<0.01),且七氟醚组FLIN量显著多于吗啡组(P<0.01)。认为七氟醚能明显抑制甲醛致痛诱导Fos蛋白在大鼠脊髓内的表达,脊髓背角是七氟醚发挥抗伤害作用的重要部位。     

口面部穴位对内脏感觉的调控作用及其途径

目的 探讨电针口面部穴位对内脏感觉的调控作用及其途径. 方法 成年SD大鼠30只,随机分为生理盐水组、内脏痛组、四白穴组、阳白穴组、颊车穴组,每组6只.生理盐水组腹腔注射0.9%生理盐水(1 ml/100 g),不给予其他任何处理;内脏痛组腹腔注射乙酸造成内脏痛模型后不给予其他任何处理;四白穴组先电针双侧四白穴20 min,再腹腔注射乙酸造成内脏痛模型;阳白穴组和颊车穴组除电针穴位不同外,其余处理同四白穴组.处理完毕后,观察大鼠的行为学变化(扭体反应)以及孤束核(NTS)和三叉旁核(PTN)的c-fos表达.结果 (1)大鼠腹腔注射0.6%的乙酸后,引发典型的内脏痛行为反应(扭体反应).电针四白穴和颊车穴预处理后,由内脏痛引发的腹部收缩次数明显减少,与内脏痛组比较均有显著差异(P<0.01,P<0.05);电针阳白穴对内脏痛大鼠腹部收缩的次数无明显影响.(2)电针四白穴预处理后,内脏痛所致NTS的c-fos表达明显减少,与内脏痛组比较有显著差异(P<0.05);电针颊车穴亦产生类似的作用;电针阳白穴作用不明显.(3)电针阳白穴预处理PTN的c-fos阳性神经元数目与内脏痛组比较无明显变化.电针四白穴预处理后,三叉旁核的c-fos表达较阳白穴组明显增加(P<0.01);电针颊车穴亦出现与四白穴类似的效应.结论 (1)电针口面部穴位对大鼠内脏痛有显著的镇痛效应,且表现出一定的穴位特异性,与穴位的神经支配密切相关.(2)面口部穴位的躯体感觉传入可能经PTN中继后与胃肠道的内脏感觉传入在NTS发生汇聚并进行整合,PTN-NTS组成的二级神经元传入通路可能是面口部穴位调节内脏功能活动的重要途径.     

脊髓背角NMDA受体NR2B亚基对舒芬太尼耐受形成的作用

目的探究脊髓背角N-甲基-D-天门冬氨酸(NMDA)受体NR2B亚基对舒芬太尼耐受形成的作用。方法将大鼠随机分为舒芬太尼组和空白对照组,皮下注射舒芬太尼复制舒芬太尼耐受大鼠模型,检测两组于皮下注射前和注射第3、9天机械性刺激痛阈和热缩足潜伏期,检测注射第3、9天脊髓背角NR2B蛋白及mRNA表达。结果舒芬太尼组注射后第3、9天机械性刺激痛阈值和热缩足潜伏期均显著大于注射前,且注射后第3天显著大于注射后第9天(P0. 05);舒芬太尼组注射后第3、9天NR2B亚基蛋白及mRNA表达水平均显著大于空白对照组,且注射后第3天均显著小于注射后第9天(P0. 05)。结论舒芬太尼诱导大鼠耐受性形成的机制可能是通过促进脊髓背角NMDA受体NR2B亚基的表达量增加。     

急性心肌损伤后大鼠孤束核的FOS核神经胶质原纤维酸性蛋白表达的变化

目的：观察急性心肌损伤后大鼠延髓孤束核(Nucleus Tractus Solitarii, NTS)神经元和星形胶质细胞的反应。方法：向心肌内注射福尔马林造成急性心肌损伤，免疫荧光染色观察NTS中Fos阳性和GFAP阳性细胞的反应情况。结果：急性心肌损伤后2 h，大鼠NTS中Fos阳性神经元显著升高，4 h达到峰值，然后开始下降。急性心肌损伤后4 h GFAP阳性星形胶质细胞荧光强度明显增强，24 h达到高峰然后下降。结论：急性心肌损伤后，大鼠延髓NTS中神经元和星形胶质细胞被心肌伤害性刺激激活，参与心肌损伤后疼痛的中枢调控。     

胃电刺激诱导大鼠延髓孤束核和迷走神经运动背核c-fos蛋白表达

背景：胃电刺激（GES）可以调控胃慢波，但其作用机制尚不完全清楚。原癌基因蛋白c—fos的表达可作为神经元功能活动的标志物。目的：以c-fos蛋白的表达为观察指标，探讨GES调控胃肌电慢波的神经机制。方法：将雌性Wistar大鼠随机分为对照组和GES组。GES以控制胃慢波为准，持续1h。分别于刺激后0．5、1、2和5h处死大鼠，以免疫组化方法观察c—fos蛋白在延髓孤束核和迷走神经运动背核中的表达。结果：对照组延髓孤束核和迷走神经运动背核仅见微量c—fos蛋白表达，GES后0．5h其表达开始增强，1h时达高峰，以后逐渐减弱。结论：GES可以调控胃肌电慢波，GES后延髓孤束核和迷走神经运动背核神经元c-fos蛋白表达阳性提示迷走神经可能参与了该调控作用。     

伤害和非伤害性结直肠扩张时脊髓和部分脑干核团的c-fos表达

目的通过检测c—Fos表达研究伤害性和非伤害性结直肠扩张（CRD）对脊髓和脑干部分核团神经元活性的影响特点。方法分别建立20、40、80mmHg重复CRD的大鼠动物模型。扩张完毕取大鼠腰骶段脊髓和脑干组织，用免疫组化染色检测c-fos阳性神经元的表达。以插入气囊但不扩张（0mmHg）大鼠为对照组。结果①40、80mmHg扩张时c-Fos阳性神经元主要分布于脊髓后角Ⅰ—Ⅵ层，以及脊髓中间带Ⅶ层和脊髓中央管附近Ⅹ层；而20mmHg时主要在脊髓后角Ⅰ-Ⅳ层表达。②40或80mmHg扩张时腰骶段脊髓c-Fos阳性神经元表达显著高于20和0mmHg（P〈0．05）。③脑干延髓（NTS）的c—Fos阳性神经元表达随扩张压力增高而增高（P〈0.05），20、40、80mmHg扩张时均显著高于对照组（P〈0．05）。④中脑导水管周围灰质（PAG）的c-Fos阳性神经元在40、80mmHg扩张时显著高于20和0mmHg，20mmHg扩张时c—Fos表达和对照组无显著差异（P〉0．05）。结论伤害和非伤害性结直肠扩张刺激可以导致不同部位神经核团的不同反应。脊髓背角以及孤束核神经元对伤害性以及非伤害性内脏扩张刺激均产生反应，而脊髓中间带以及PAG神经元可能仅对伤害性内脏扩张刺激发生显著反应。     

Fos expression incatecholaminergic medullary neu-rons induced by chemical stimulation of stomach projecting to the paraventricular nucleus of hypothalamus in rats

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Effects of tegaserod on Fos, substance P and calcitonin gene-related peptide expression induced by colon inflammation in lumbarsacral spinal cord

AIM: To investigate the mechanisms of tegaserod, a partial 5-HT4 agonist, in reducing visceral sensitivity by observing Fos, substance P (SP) and calcitonin gene-related peptide (CGRP) expression in the lumbarsacral spinal cord induced by colonic inflammation in rats. METHODS: Twenty-four male rats with colonic inflammation induced by intraluminal instillation of trinitrobenzenesulfonic acid (TNBS) were divided into 3 groups. Treatment group 1: intra-gastric administration of tegaserod, 2 mg/kg.d; Treatment group 2: intra-gastric administration of tegaserod, 1 mg/kg.d; Control group: intra-gastric administration of saline, 2.0 mL/d. After 7 d of intra-gastric administration, lumbarsacral spinal cord was removed and processed for Fos, SP and CGRP immunohistochemistry. RESULTS: In rats of the control group, the majority of Fos labeled neurons was localized in deeper laminae of the lumbarsacral spinal cord (L(5)-S(1)). SP and CGRP were primarily expressed in the superficial laminae of the spinal cord after TNBS injection. Intra-gastric administration of tegaserod (2 mg/kg.d) resulted in a significant decrease of Fos labeled neurons (22.0+/-7.7) and SP density (12.5+/-1.4) in the dorsal horn in the lumbarsacral spinal cord compared to those of the control group (62.2+/-18.9, 35.9+/-8.9, P<0.05). However, CGRP content in dorsal horn did not significantly reduce in rats of treatment group 1 (1.2+/-1.1) compared to that of the control group (2.8+/-2.4, P>0.05). Neither Fos expression nor SP or CGRP density in the dorsal horn significantly declined in rats of treatment group 2 compared to those of the control group (P>0.05). CONCLUSION: Tegaserod can significantly reduce Fos labeled neurons in the lumbarsacral spinal cord induced by colonic inflammation. Tegaserod may reduce visceral sensitivity by inhibiting SP expression in the dorsal horn of spinal cord.     

Fos expression in tyrosine hydroxylase-containing neurons in rat brainstem after visceral noxious stimulation： an immunohistochemical study

AIM: To prove that neurons in the different structures of the brainstem that express tyrosine hydroxylase (TH) are involved in the transmission and modulation of visceral or somatic nociceptive information in rat. METHODS: Immunohistochemical double-staining method was used to co-localize TH and Fos expression in neurons of the rat brainstem in visceral or subcutaneous noxious stimulation models. RESULTS: Neurons co-expressing TH/Fos were observed in lateral reticular nucleus (LRT), rostroventrolateral reticular nucleus (RVL), solitary tract nucleus (SOL), locus coeruleus (LC), A5, A7 neuronal groups and ventrolateral subdivision of the periaqueductal gray (vlPAG) in both models. But the proportion and number of the double-labeled neurons responding to the two noxious stimuli were significantly different in the LRT, RVL and LC nuclei. The proportion and number of the TH/Fos double-labeled neurons in the visceral pain model were smaller than that in the subcutaneous pain model. However, in the case of SOL, they were similar in the two models. CONCLUSION: Differences of Fos expression in TH immunoreactive neurons in animals after visceral and somatic noxious stimulation indicate that the mechanisms of the transmission and modulation of visceral nociceptive information in the brainstem may be different from that of somatic nociceptive information.     

High cervical midline punctate myelotomy in the management of visceral pain in the mouse

Increasing evidence implies the existence of a visceral pain pathway in the dorsal column of the spinal cord. Limited midline myelotomy has been used to treat intractable pelvic cancer pain. However, no obvious evidence has been provided that high cervical punctate midline myelotomy (CPMM) relieves visceral pain originating from the abdomen. This study was designed to examine the pain relief effect of CPMM in a mouse model of visceral pain. Thirty-six Institute of Cancer Research (ICR) mice were divided into three groups: Group 1, healthy controls; Group 2, treated with CPMM at C1 and C2; and Group 3, a sham group that underwent laminectomy at C1 and C2 without CPMM. All animals were tested for antinociception in the writhing test 24 hours after surgery. Visceral pain-related behaviors were counted from 5-20 minutes after intraperitoneal injection of 0.6% acetic acid. Writhing test scores were not significantly different between Groups 1 (56.7 +/- 10.7) and 3 (50.7 +/- 17.4). However, Group 2 (30.0 +/- 14.3) showed more than 40% antinociception after treatment, and writhing test scores were significantly different from those of Groups 1 and 3 (p < 0.001). Our results confirm that midline punctate myelotomy can relieve visceral pain and imply that there is a pathway in the posterior funiculus that signals visceral pain. Punctate midline myelotomy at the cervical or high thoracic level may be an alternative strategy in the management of intractable visceral pain due to abdominal or pelvic cancers.     

Fos expression in catecholaminergic medullary neurons induced by chemical stimulation of stomach projecting to the paraventricular nucleus of the hypothalamus in rats

AIM: To determine whether medullary catecholaminergic neurons expressing Fos induced by chemical stimulation of the stomach project to the paraventricular nucleus of hypothalamus (PVH) in rats.METHODS: Horseradish peroxidase (HRP) was introduced stereotaxically into the PVH of rats. Histochemical analysis of coronal sections through the medulla were analyzed using triple-label immunohistochemistry to identify cells that were retrogradely labeled with HRP, Fos (ABC method), and tyrosin hydroxylase (TH) (PAP method).RESULTS: Seven kinds of labeled neurons were found in the nucleus tractus solitarii (NTS), the ventrolateral medulla (VLM) and the reticular formation (RF) of the medulla: Fos-like immunoreactive (FosLI) neurons, TH-like immunoreactive (TH-LI) neurons and HRP retrogradely single-labeled neurons, FosLI/HRP, FosLI/TH-LI and HRP/TH-LI double-labeled neurons, and FosLI/HRP/TH-LI triple-labeled neurons.CONCLUSION: Ascending projections from the NTS, VLM and RF to the PVH might be involved in the transmitting process of visceral noxious stimulation.     

Minocycline completely reverses mechanical hyperalgesia in diabetic rats through microglia-induced changes in the expression of the potassium chloride co-transporter 2 (KCC2) at the spinal cord

Aim: Neuronal hyperactivity at the spinal cord during mechanical hyperalgesia induced by diabetes may result from a decrease in the local expression of the potassium chloride co‐transporter 2 (KCC2), which shifts the action of the neurotransmitter γ‐amminobutiric acid (GABA) from inhibitory to excitatory. In this study, we evaluated the effects of spinal microglia inhibition or brain‐derived neurotrophic factor (BDNF) blockade on KCC2 expression, spinal neuronal activity and mechanically induced pain responses of streptozotocin (STZ)‐diabetic rats. Methods: Four weeks after induction of diabetes, the STZ‐diabetic rats received daily intrathecal injections, for 3 days, of minocycline (microglia inhibitor), TrkB/Fc (BDNF sequester) or saline. Behavioural responses to mechanical nociceptive stimulation of STZ‐diabetic rats were evaluated by the Randall‐Selitto test. The lumbar spinal cord was immunoreacted against the Fos protein (marker of neuronal activation) or KCC2, which was also quantified by western blotting. BDNF levels at the spinal cord were quantified by an enzyme‐linked immunosorbent assay (ELISA). Results: Minocycline treatment reversed the mechanical hyperalgesia, increased Fos expression and decreased the KCC2 expression detected in STZ‐diabetic rats to control levels. Treatment with TrkB/Fc was less effective, inducing moderate effects in mechanical hyperalgesia and Fos expression and only a partial correction of KCC2 expression. BDNF levels were not increased in STZ‐diabetic rats. Conclusions: This study demonstrates that the microglial activation at the spinal cord contributes to mechanical hyperalgesia and spinal neuronal hyperactivity induced by diabetes, apparently by regulating the KCC2 expression. These effects do not seem to be mediated by BDNF, which is an important difference from other chronic pain conditions. New targets directed to prevent spinal microglia activation should be considered for the treatment of mechanical hyperalgesia induced by diabetes.     

小胶质细胞在偏头痛大鼠中枢敏化过程中的作用

目的观察二甲胺四环素(MC)对偏头痛大鼠痛觉超敏行为、颈髓后角小胶质细胞及神经元激活的影响,探讨小胶质细胞在偏头痛大鼠模型中枢敏化过程中的作用。方法 66只雄性SD大鼠随机分为空白组、假手术组、生理盐水组(NS组)、新型致炎剂(IS)4d组(IS4组)、IS 7d组(IS7组)、IS/MC预防组、IS/NS预防组、NS/NS预防组、IS/MC治疗组、IS/NS治疗组、NS/NS治疗组。每组6只。采用Vonfrey纤维丝测定各组大鼠眶周痛觉阈值,免疫荧光染色测定颈髓后角小胶质细胞及神经元激活情况。结果硬脑膜给予IS第3天眶周痛觉阈值较NS组明显下降(P<0.01)。IS/MC预防组眶周痛觉阈值明显高于IS/NS预防组(P<0.01)。IS4组、IS7组小胶质细胞平均荧光密度值高于假手术组(P<0.01)。IS/MC预防组、IS/MC治疗组小胶质细胞平均荧光密度值分别低于IS/NS预防组、IS/NS治疗组(P<0.01)。IS/MC预防组C-fos平均荧光密度值明显低于IS/NS预防组(P<0.01)。结论在慢性硬脑膜炎症所致的中枢敏化过程中小胶质细胞可能仅在启动阶段起作用,对于痛觉超敏的维持无作用。MC能有效预防偏头痛大鼠模型痛觉超敏的发生,但对已存在的痛觉超敏无治疗作用。     

GFAP and Fos immunoreactivity in lumbo-sacral spinal cord and medulla oblongata after chronic colonic inflammation in rats

AIM: To investigate the response of astrocytes and neurons in rat lumbo-sacral spinal cord and medulla oblongata induced by chronic colonic inflammation, and the relationship between them. METHODS: Thirty-three male Sprague-Dawley rats were randomly divided into two groups: experimental group (n = 17), colonic inflammation was induced by intra-luminal administration of trinitrobenzenesulfonic acid (TNBS); control group (n = 16), saline was administered intra-luminally. After 3, 7, 14, and 28 d of administration, the lumbo-sacral spinal cord and medulla oblongata were removed and processed for anti-glial fibrillary acidic protein (GFAP), Fos and GFAP/Fos immunohistochemistry. RESULTS: Activated astrocytes positive for GFAP were mainly distributed in the superficial laminae (laminae Ⅰ-Ⅱ) of dorsal horn, intermediolateral nucleus (laminae Ⅴ), posterior commissural nucleus (laminae Ⅹ) and anterolateral nucleus (laminae Ⅸ). Fos-IR (Fos-immunoreactive) neurons were mainly distributed in the deeper laminae of the spinal cord (laminae Ⅲ-Ⅳ, Ⅴ-Ⅵ). In the medulla oblongata, both GFAP-IR astrocytes and Fos-IR neurons were mainly distributed in the medullary visceral zone (MVZ). The density of GFAP in the spinal cord of experimental rats was significantly higher after 3, 7, and 14 d of TNBS administration compared with the controls (50.4±16.8, 29.2±6.5, 24.1±5.6, P<0.05). The density of GFAP in MVZ was significantly higher after 3 d of TNBS administration (34.3±2.5, P<0.05). After 28 d of TNBS administration, the density of GFAP in the spinal cord and MVZ decreased and became comparable to that of the controls (18.0±4.9, 14.6±6.4,P>0.05). CONCLUSION: Astrocytes in spinal cord and medulla oblongata can be activated by colonic inflammation. The activated astrocytes are closely related to Fos-IR neurons. With the recovery of colonic inflammation, the activity of astrocytes in the spinal cord and medulla oblongata is reduced.     

电针对糖尿病胃轻瘫大鼠胃电活动与延髓神经元和星状胶质细胞可塑性的影响

[目的]观察电针对糖尿病胃轻瘫（DGP）大鼠胃电活动与延髓迷走孤束复合体（VSC）内神经元和星状胶质细胞可塑性变化的影响。[方法]实验大鼠分为空白对照（空白）组、DGP模型（模型）组、模型加电针足三里穴（足三里）组和模型加电针三阴交穴（三阴交）组。模型制备采用腹腔注射5％四氧嘧啶和熟地灌胃诱导的方法。实验3周后记录大鼠的胃电活动,取延髓进行抗Fos蛋白和抗胶质原纤维酸性蛋白（GFAP）的免疫组化染色。[结果]与空白组比较,模型组的胃电平均频率和振幅明显降低。而足三里组和三阴交组的平均频率和振幅较模型组明显升高（P〈O．01,〈0．05）;以足三里组升高更明显,与三阴交组比较差异有统计学意义（P〈0．05）。除空白组外,Fos阳性神经元、GFAP阳性星状胶质细胞集中表达于VSC。以模型组的Fos和GFAP表达最高,而足三里组与三阴交组的表达较模型组明显减少,且它们之间差异有统计学意义（P〈0．01）。[结论]针刺可改善糖尿病胃运动功能障碍,延髓VSC内免疫阳性神经元和胶质细胞可能参与了此调节作用。     

Gastric distention enhances FOS and calcitonin gene‐related peptide expression in the spinal cord and brain of rats

OBJECTIVE: The purpose of this study was to determine the pathway and mode of transmission of visceral stimuli by investigating the distribution of the FOS and calcitonin gene‐related peptide (CGRP) proteins in the central nervous system. METHODS: Twenty‐four Sprague‐Dawley rats were divided into three groups: study group (n = 12), sham control group (n = 6), and normal control group (n = 6). A balloon was implanted into the stomach of the rats in the study and sham control groups. After 48 h, the rats in the study group had the stomach distended (80 mmHg) for 2 h, after which they were killed and the antrum, thoracic spinal cord and brain were isolated or dissected. The expression of Fos and CGRP in these tissues was detected immunohistochemically. RESULTS: FOS expression in the dorsal horn of the spinal cord, dorsal nucleus of the vagal nerve, nucleus of the solitary tract in the study rats was significantly higher than in the sham and normal controls. However, no difference was found between the three groups in FOS expression in the myenteric plexus. Similarly, gastric distention enhanced CGRP expression significantly in the spinal cord and medulla oblongata and correlated closely with FOS expression in these two areas. CONCLUSIONS: Gastric distention can activate the limbic system, and CGRP plays an important role in the input of visceral stimuli.