血管活性肠肽对MPTP亚急性帕金森病模型小鼠突触的影响

目的 探讨血管活性肠肽(VIP) 对1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的帕金森病(PD)小鼠模型突触及其行为学的影响. 方法 雄性C57BL/6 J小鼠30只,随机分为生理盐水(NS)组、MPTP组、MPTP+VIP组。利用Tru Scan系统测定小鼠的行为学变化;免疫组织化学染色法检测黑质和纹状体区酪氨酸羟化酶(TH)的表达及纹状体区突触小泡膜蛋白 2（VAMP2）和突触素1 (SYN1)的表达变化;运用免疫印迹法检测VAMP2和SYN1的表达变化;并通过透射电子显微镜观察黑质区突触的结构改变。 结果 行为学结果统计学分析,MPTP组小鼠的垂直运动距离比对照组明显减少,而给予VIP的小鼠明显高于MPTP组小鼠。 MPTP组TH、VAMP2和SYN1表达均明显少于NS组,而MPTP+VIP组显著高于MPTP组。透射电子显微镜结果显示,NS组神经突触结构完整; 模型组神经突触数量少,突触间隙不清,突触前成分的线粒体出现髓样变,并且突触小泡数量减少;MPTP+VIP组神经突触结构基本正常。 结论 VIP可使MPTP模型小鼠VAMP2和SYN1的表达上调,减少突触结构的损伤,保护黑质纹状体系统TH的表达,从而改善其运动状态。     

血管活性肠肽的免疫调节作用

血管活性肠肽是一种神经肽 ,又是一种小分子免疫活性肽。随着与相应血管活性肠肽受体的cDNAs被克隆和表达 ,对血管活性肠肽的免疫学作用也有了更深入的认识。血管活性肠肽通过影响细胞因子的产生、调节炎症反应、影响胸腺细胞的分化、调节Th细胞应答来参与免疫自稳的调节 ,并可抑制T淋巴细胞的凋亡、抑制T细胞介导的细胞毒作用     

025 血管活性肠肽的免疫调节作用

血管活性肠肽是一种神经肽，又是一种小分子免疫活性肽。随着与相应血管活性肠肽受体的cDNAs被克隆和表达，对血管活性肠肽的免疫学作用也有了更深入的认识。血管活性肠肽通过影响细胞因子的产生、调节炎症反应、影响胸腺细胞的分化、调节Th细胞应答来参与免疫自稳的调节，并可抑制T淋巴细胞的凋亡、抑制T细胞介导的细胞毒作用。     

血管活性肠肽的免疫调节作用

血管活性肠肽是一种神经肽，又是一种小分子免疫活性肽。随着与相应血管活性肠肽受体的cDNAs被克隆和表达，对血管活性肠肽的免疫学民有了更深入的认识。血管活性肠肽通过影响细胞因子的产生、调节炎症反应、影响胸腺细胞的分化、调节Th细胞应答来参与免疫自稳的调节，并可抑制T淋巴细胞的凋亡、抑制T细胞介导的细胞毒作用。     

血管活性肠肽与神经免疫调节

近年发现,血管活性肠肽不仅对局部粘膜中免疫细胞的增殖,分化,活化及其在局部粘膜中的定位有一定调节作用,而且对免疫细胞分泌多种细胞因子以及合成免疫球蛋白也有一定的促进或抑制作用,本文就血管活性肠肽在体内的分布以及在免疫系统的调节及机制作如下综述。     

血管活性肠肽免疫调节作用的研究进展

血管活性肠肽(VIP)是一种广泛分布的神经肽,其作为信号分子在神经-内分泌-免疫网络中扮演着重要的角色,在免疫系统中,VIP被认为能够通过调节固有免疫和适应性免疫来发挥内源性的免疫调节作用,其能抑制巨噬细胞的促炎反应,调节Th2/Th1的平衡,并促进调节性T细胞的生成,抑制Th17细胞效应,在炎症动物模型如胶原诱导的关节炎、自身免疫性脑脊髓炎中都起到明显作用。现就近年来有关血管活性肠肽的免疫调节机制进行综述,以增进对血管活性肠肽发挥抗炎作用的理解。     

血管活性肠肽对树突状细胞免疫调节作用研究进展

神经系统与免疫系统通过神经肽、神经递质和细胞因子相互作用。血管活性肠肽(VIP)作为一种重要的神经肽参与炎症反应和免疫应答的调控。近年研究表明VIP能通过与树突状细胞(DC)表面的受体结合调节DC的表型和功能成熟,在DC体内迁移和功能成熟中发挥重要作用。VIP主要通过调节DC膜表面黏附分子和共刺激分子的表达、趋化因子及其受体的表达和趋化活性,诱导Th细胞分化以及抗原提呈功能发挥作用。     

血管活性肠肽对帕金森病大鼠黑质多巴胺能神经元存活及小胶质细胞功能的影响

目的:观察血管活性肠肽(VIP)对帕金森病(PD)大鼠黑质多巴胺(DA)能神经元存活和小胶质细胞活化的影响。方法:采用脑立体定位术将6-羟多巴胺注射至纹状体,制备大鼠PD模型。将PD大鼠随机分为VIP组和模型组,VIP组大鼠腹腔注射VIP 1 ml(20 ng/ml)。另10只正常大鼠为对照组。采用免疫组织化学和RT-PCR方法观测各组大鼠黑质DA能(酪氨酸羟化酶(TH)阳性)神经元数量、小胶质细胞(CD11b阳性)的数量和形态变化以及肿瘤坏死因子(TNF-α)和环氧酶-2(COX-2)的表达及相关分子mRNA水平达变化。结果:PD大鼠损毁侧黑质TH阳性神经元数量较对照组明显减少(P0.05),小胶质细胞(CD11b阳性细胞)数量显著增加(P0.05),并呈"阿米巴"样改变,TNF-α和COX-2阳性细胞数量明显增加(P0.05);VIP组大鼠与模型组相比,黑质TH阳性神经元数量明显增加(P0.05),CD11b阳性细胞数量明显减少(P0.05),TNF-α和COX-2的阳性细胞数量显著减少(P0.05)。RT-PCR检测结果可见,模型组大鼠黑质TH mRNA较对照组显著降低,而VIP组TH mRNA较模型组显著升高(P0.05),模型组CD11b mRNA、TNF-αmRNA表达明显高于对照组,而VIP组大鼠CD11b mRNA、TNF-αmRNA表达显著低于模型组。结论:VIP对6-OHDA所致PD大鼠DA能神经元具有保护作用,并且可以抑制黑质内小胶质细胞活化及相关炎性因子的表达。     

血管活性肠肽（VIP）放免分析方法探讨

血管活性肠肽(VIP)是一种含28个氨基酸的硷性多肽,1970年首次在猪小肠分离提取;此后一系列研究证明,VIP在体内分布广泛,参与多种重要生理活动。近年来有关VIP的病理生理作用已引起人们关注。鉴于国内对VIP的放射免疫分析(RIA)方法尚少专题研究,我们参考有关文献。并进行了一些改进,建立了VIP的RIA,并测定了17例麻醉狗血浆、脑脊液(CSF)及3例脑组织匀浆的VIP浓度。现将方法及结果报告如下。     

扬子鳄泄殖腔壁内血管活性肠肽的分布

目的：观察含血管活性肠肽（VIP）神经在爬行类动物－扬子鳄泄殖腔壁内的分布特点。方法：免疫组织化学ABC法及免疫荧光法。结果：扬子鳄泄殖腔壁内VIP免疫反应阳性神经纤维见于粘膜下层及肌层,呈串珠状,大致与平滑肌纤维平行走行,并见其分支在实质内构成网络状,但明显伴血管走行的纤维稀少。通过免疫荧光法证实,粘膜下层内存在VIP免疫反应阳性细胞,胞体大小、形态不一。结论：扬子鳄泄殖腔已具备了类似高等脊椎动物的含VIP神经的调节。     

Peptidergic (vasoactive intestinal peptide) nerves in the genito-urinary tract

The feline genito-urinary tract receives a rich supply of nerve fibers displaying immuno-reactivity like that of vasoactive intestinal peptide. Nerves containing vasoactive intestinal peptide are particularly numerous in the trigonum area of the bladder, around the ureteral openings and in the upper part of the urethra in both sexes, in the epididymis, prostate and vas deferens, and in the uterine cervix. Ganglia located close to or within the wall of the trigonum area and of the upper urethra contain numerous immunoreactive nerve cell bodies, which may be the origin of the fibers containing vasoactive intestinal peptide that innervate these regions.     

Developmental studies on vasoactive intestinal peptide,substance P and calcitonin gene-related peptide in salivary glands of postnatal rats

The development of vasoactive intestinal peptide, substance P and calcitonin gene-related peptide in parotid, submandibular and sublingual glands of the male rat was followed by immunochemistry and immunocytochemistry. The total amounts of these peptides increased in surges during the first 8 weeks of the animal's life; one within 2–4 weeks and the other beginning 1–2 weeks later. Nerve fibres containing these peptides were present at birth showing a pattern of distribution similar to that in adults. During the first 4 weeks the nerve fibres increased in number.     

Distribution of vasoactive intestinal polypeptide in the rat and mouse brain.

The distribution of cell bodies and nerve fibers that combine with antisera to vasoactive intestinal polypeptide (VIP) was studied by immunohistochemistry in combination with radioimmunoassay in the brain of rat and mouse. The highest concentrations (60pmol/g wet wt) of immuno-reactive VIP were found in the cerebral cortex and in certain limbic structures, whereas the concentrations in the basal ganglia, thalamus, lower brain stem, cerebellum and spinal cord were low (<15pmol/g). VIP-immunoreactive cell bodies were found mainly in the cerebral cortex and the limbic system, with the great majority of them in neo- and allocortical areas. In the neocortex the VIP-containing cell bodies were found in layers II-V in all areas. The cells were fusiform or stellate shaped, resembling intracortical and corticocortical association neurones. In the pyriform and entorhinal cortex the cell bodies were located mainly in layer II. In the hippocampal complex VIP-containing cell bodies occurred in both the subiculum, areas CA1 and CA3 and the dentate gyrus. Most of the cells had the appearance of interneurones, some of them probably being identical with basket cells. Of subcortical areas, the amygdala had the largest number of VIP-containing cell bodies; they were numerous in all amygdaloid nuclei except in the central nucleus. Non-cortical areas where there were cell bodies containing VIP included the anterior olfactory nuclei, the bed nucleus of stria terminalis, lateral septum, suprachiasmatic nucleus, superior colliculus, and the mesencephalic periaqueductal gray.VIP-immunoreactive fibres had a distribution which on the whole paralleled that of the cell bodies, suggesting that many of the VIP-containing cells project locally. VIP-containing fibres were numerous in the following areas: the entire neocortex, the pyrifom cortex, the entorhinal cortex, the hippocampal complex, the amygdala (the central nucleus in particular), the anterior olfactory nuclei, the nucleus accumbens, ventral pallidum, bed nucleus of stria terminalis, suprachiasmatic nucleus, medial preoptic nucleus, median eminence, lateral geniculate body, pretectum, superior colliculus, periaqueductal gray, and the lateral parabrachial nucleus. Only few, scattered fibres were seen in other parts of the brain stem, in the striatum, thalamus and spinal cord. The cerebellum was devoid of VIP-containing fibres. VIP-containing neurones seem to form predominantly local projections. In addition, some VIP-containing neurones probably also form long projections, such as descending and transcallosal projections from the cortical cells, and projections from the amygdala to preoptic, hypothalamic and basal forebrain areas.The characteristic telencephalic distribution of the neurones that contain VIP suggests a role for this peptide in cortical and limbic functions.     

Low levels of vasoactive intestinal peptide are associated with Chagas disease cardiomyopathy

The interconnection between immune and neuroendocrine systems influences regulation of inflammatory responses. The possible relevance that this integrative response may have during the course of Chagas disease remains poorly characterized. In this context, our study was designed to determine the expression of vasoactive intestinal peptide (VIP), a neuropeptide with anti-inflammatory properties, in blood from the indeterminate and cardiac polarized forms of Chagas disease. Moreover, we determined whether the differential expression of VIP is associated with the development of cardiomyopathy in individuals infected with Trypanosoma cruzi. Finally, we analyzed gene polymorphisms of VIP receptors, VPAC1 and VPAC2, and performed correlation analysis of these polymorphisms with the different clinical forms of Chagas disease. Our results demonstrated that low plasma levels of VIP were associated with the cardiac morbidity in Chagas disease. Accordingly, correlation analysis showed that low plasma levels of VIP were associated with worse cardiac function, as determined by left ventricular ejection fraction and left ventricular diastolic diameter values. Polymorphism analysis showed a significant association between VPAC1 and the indeterminate form of Chagas disease development. Our data indicate that VIP expression and its receptors’ polymorphism may be important in determining susceptibility to progression from mild to severe forms of Chagas disease.     

红景天苷对MPTP诱导的帕金森病小鼠黑质多巴胺转运蛋白的影响

目的:探讨红景天苷(salidroside,Sal)对帕金森病(Parkinson’s disease,PD)小鼠黑质多巴胺转运蛋白(dopamine transporter,DAT)表达的影响。方法:将神经毒素1-甲基-4苯基-1,2,3,6-四氢吡啶(1-methyl-4-phen-yl-1,2,3,6-tetrahydropyridine,MPTP)注入C57BL/6小鼠腹腔内,制备PD模型,Rotarod实验和游泳实验观察小鼠行为学变化,免疫荧光组织化学法检测黑质DAT阳性神经元数目的变化。结果:行为学实验结果显示,Rotarod实验中模型组小鼠在滚轴上运动的时间明显短于正常组(P<0.01),给予不同剂量的Sal后,小鼠在滚轴上运动的时间有所延长,并呈剂量依赖性(P<0.05,P<0.01)。游泳实验结果与Rotarod结果一致,模型组小鼠游泳时间明显短于正常组(P<0.01),给予不同剂量Sal后,小鼠游泳时间不同程度增加(P<0.05,P<0.01)。免疫荧光结果显示,模型组小鼠黑质中DAT阳性神经元的数目明显少于正常组(P<0.01),而给予不同剂量Sal干预后,小鼠DAT阳性神经元数目的减少有所恢复(P<0.05,P<0.01)。结论:Sal可以改善PD小鼠行为协调能力,提高DAT阳性神经元存活的数目,并呈剂量依赖性,表明Sal对多巴胺(dopamine,DA)能神经元具有一定的保护作用。     

Substance P and vasoactive intestinal peptide in serotonin-induced nasal secretions in normal subjects

The aim of this study was to examine if nasal secretions contained substance P and/or vasoactive intestinal peptide. Serotonin nasal challenge was performed in 14 normal subjects 15 min after intranasal pretreatment (double-blind) with atropine, methysergide, chlorpheniramine or isotonic saline. Serotonin induced a dose dependent increase in secretion (P less than 0.05), and only pretreatment with atropine reduced the secretion (P less than 0.02). Substance P, measured by radioimmunoassay, was found in all of the examined secretions (n = 100) with a median concentration of 13.7 pmol/l (range 1.7-125.0). Serotonin challenge increased the concentration or content of substance P in a dose-related fashion (P less than 0.01). The different pretreatments did not affect the concentration of substance P. Vasoactive intestinal peptide was found in low concentration in 37% of the secretions with a median concentration of 0 pmol/l (range 0-50.0).     

Interaction of cholecystokinin with vasoactive intestinal peptide in body shaking response to ice-water immersion in rats

Interaction of cholecystokinin (CCK) with vasoactive intestinal peptide (VIP) in body shaking response to ice-water immersion was observed in pentobarbital-anesthetized rats. Although CCK itself had no influence on the response, VIP suppressed it and this effect of VIP was antagonized by simultaneous administration of sulfated octapeptide of CCK, but not by non-sulfated CCK.     

Effect of nasal allergen challenge on serotonin, substance P and vasoactive intestinal peptide in plasma and nasal secretions

We have studied the changes in concentration of serotonin, substance P, and vasoactive intestinal peptide (VIP) in plasma following a nasal allergen provocation in 14 grass pollen-allergic subjects; in five the urinary excretion of serotonin and 5-hydroxy-indolyl-acetic acid (5-HIAA) was also measured. In addition, the concentration of serotonin and substance P was measured in nasal secretions following nasal challenge with allergen and methacholine. The results showed an allergen-induced increase in free plasma serotonin (P less than 0.01) and no change in platelet serotonin, urinary serotonin and urinary 5-HIAA. The plasma substance P level tended to fall (P greater than 0.1), while plasma VIP increased significantly (P less than 0.02). In nasal secretions, there were measurable levels of serotonin in all samples and of substance P in all but one. There was no difference between the concentrations of serotonin and substance P in secretions collected after allergen challenge and after methacholine challenge. For both substances, the secretion median value was comparable to that of plasma. Symptom reduction by topical and systemic pretreatment with a serotonin- and VIP-antagonist before nasal allergen provocation is necessary to define the role of these two agents in allergic rhinitis.     

胎儿小肠生长抑素、胃泌素及血管活性肠肽免疫反应细胞的个体发生

目的：探讨生长抑素（SS）、胃泌素（Gas）、血管活性肠肽（VIP）免疫反应（IR）细胞在胎儿小肠中的个体发生及其分布。方法：免疫组织化学方法和图像分析技术。结果：SS-IR细胞和Gas-IR细胞于11周即可见于小肠三段绒毛上皮和尚未分化完全的肠腺细胞间。随着胎龄增长,SS-IR细胞数量和细胞内SS由少至多,其中以十二指肠细胞最多,回肠最少。Gas-IR细胞和细胞内的Gas在十二指肠中随胎龄增长逐渐增多;21周后空肠中则有所减少,回肠中则消失。VIP-IR细胞数量少,整个胎期细胞数量、形态及免疫染色强度均未见明显变化。结论：SS、Gas和VIP在胎儿小肠的内分泌细胞中表达,提示内分泌激素在胎儿小肠的发育过程中起调节作用。     

磷酸化P38 MAPK对帕金森病MPTP模型小鼠黑质caspase-3表达的影响

目的研究磷酸化P38 MAPK在1-甲基-4-苯基-1,2,3,6四氢吡啶(MPTP)所致帕金森病(PD)模型小鼠中对黑质半胱氨酸蛋白酶-3(caspase-3)的调控作用。方法将小鼠随机分为MPTP模型组,腹腔注射MPTP(30mg/kg,生理盐水溶);抑制剂组,在注射MPTP前1h腹腔注射SB203580(10mg/kg,溶于5mg/mLDMSO)。均1次/d,连续5d;对照组,注射与模型组和抑制剂组等量生理盐水和DMSO。观察行为学、免疫组织化学和免疫蛋白印迹法观察黑质酪氨酸羟化酶(TH)、caspase-3和磷酸化P38 MAPK(p-P38MAPK)的表达。结果与对照组相比,模型小鼠出现典型的PD症状,TH阳性神经元和蛋白水平分别下降约60%和65%(P<0.01),p-P38 MAPK、caspase-3阳性细胞及蛋白水平显著增加(P<0.01);经P38 MAPK抑制剂SB203580处理后,上述变化均显著减轻(P<0.01)。结论磷酸化P38 MAPK在MPTP诱导的PD小鼠黑质caspase-3表达中可能有重要调控作用,SB203580对PD小鼠具有一定的神经保护作用。