降钙素基因相关肽对脑缺血大鼠脑血流的影响

大鼠侧脑室注入降钙素基因相关肽（ＣＧＲＰ）或等体积甘露醇为对照，用非损伤阻抗法测定一侧颈总动脉结扎后ＣＧＲＰ对脑血流的影响。结果表明，一侧颈总动脉结扎后，脑血流量降低３４％，此时侧脑室给予ＣＧＲＰ即刻使脑血流图波幅增加，５分钟时达高峰，比注药前平均增加６５％，与甘露醇对照相比差别非常显著（Ｐ＜０．０１），４０分钟时作用开始减弱，１００分钟后作用消失。与颈总动脉结扎前相比，在脑血供不足时，ＣＧＲＰ增     

降钙素基因相关肽拮抗内皮素生物效应的研究

本实验在大鼠及小鼠的整体、离体器官及细胞水平上系统观察了降钙素基因相关肽对内皮素的拮抗作用。结果表明，ＣＧＲＰ显著地拮抗ＥＴ的升压、增加血管张力、促进血管平滑肌细胞增殖、损伤心肌以及致小鼠猝死等作用，并明显降低大鼠血浆ＥＴ含量。结果提示ＣＧＲＰ可能是机体内源性ＥＴ拮抗剂，给予外源ＣＧＲＰ可能对与ＥＴ有关的心脑血管疾病有防治意义。     

慢性心力衰竭时心肌和血浆中CGRP含量的变化

目的研究大鼠心肌组织和血浆中降钙素基因相关肽(CGRP)含量变化与慢性心力衰竭(CHF)发生、发展过程中的关系,揭示CGRP在CHF时的作用机制,为CHF的治疗提供新的思路。方法腹腔注射阿霉素(ADR)制备慢性心衰大鼠模型,采用放射免疫学方法对心肌组织和血浆中CGRP含量进行检测。结果实验结果显示,在CHF发生发展过程中,血浆中CGRP的含量经历了先下降后升高的过程;而心肌组织中CGRP含量逐渐升高。结论血浆中CGRP含量在CHF的不同时程和阶段变化不一,与CGRP对CHF时对心肌的保护作用和多组织来源有关;心肌组织中CGRP含量逐渐升高与损伤刺激和心肌代偿作密切相关。     

大鼠肺内的降钙素基因相关肽

应用特异的放射免疫测定和免疫组织化学方法,证明大鼠肺内存在降钙素基因相关肽(CGRP)。肺提取物的凝胶层析所获得的CGRP免疫活性峰表明大鼠肺内的CGRP是以单一分子形式存在的。实验对CGRP在肺内的分布进行了探讨。大鼠肺动脉离体实验表明CGRP有很强的肺动脉舒张作用。     

慢性心力衰竭时心肌组织中CGRP的含量变化及mRNA表达

目的探讨心肌组织降钙素基因相关肽(CGRP)含量变化及mRNA的表达与慢性心力衰竭(CHF)发生、发展的关系。方法以阿霉素(ADR)制备慢性心衰模型,采用放射免疫学方法和逆转录聚合酶链反应进行检测。结果CHF时,心肌组织中CGRP含量为34.82±3.01,高于正常心肌组织中CGRP的含量24.77±3.84,差异具有统计学意义;而CGRP的mRNA表达降低。结论心肌组织中CGRP含量变化及其mRNA的表达调控,与CHF的发生、发展密切相关。     

内毒素血症幼年大鼠心肌降钙素基因相关肽的动态变化及谷氨酰胺、地塞米松对其影响

目的 通过观察内毒素血症幼年大鼠心肌降钙素基因相关肽(calcitonin gene-related peptide,CGRP)的动态变化及谷氨酰胺(glutamine,Gin)、地塞米松(dexamethosone,Dex)对其影响,探讨CGRP对内毒素血症大鼠心肌的保护作用.方法 选用健康18日龄Wistar大鼠128只,按腹腔注射药物不同分为:Oh对照组(Ctrl:生理盐水,n=8),内毒素血症组(LPS:n=40)、谷氨酰胺组(Gin,n=40),地塞米松组(Dex,n=40),后3组又分为2、4、6、24及72h 5个时点,每个时点8只,在各指定时点分别将大鼠断头分离心脏,用放射免疫方法测定心肌CGRP表达水平.结果 1.与对照组比较,各组心肌组织内CGRP均下降,P＜0.05～0.01;LPS组CGRP下降最明显,最低点在6h,Gin和Dex组最低点均后延至24h,Gin降低最轻,但3组最低点之间无显著差别,P＞0.05.2.在内毒素血症早期,Dex组下降最慢,但在恢复期,Gln组恢复最快,虽明显高于LPS组,但仍显著低于Oh对照组,P＜0.05.结论 Gln和Dex具有抑制CGRP下降的作用,其中Dex抑制早期CGRP下降作用较大,而Gln促进恢复作用更明显.     

高原低氧对血浆降钙素基因相关肽含量的影响

降钙素基因相关肽(calcitonin gene-related peptide,CGRP)是目前已知的最强的非肾上腺素能、非胆碱能受体型血管舒张活性物质[1]。在人体肺循环对高原低氧的适应性生理反应中CGRP发挥着重要作用。肺自身也在CGRP浓度的动态平衡方面起调节作用。1材料与方法1·1研究对象:①世居     

先兆子痫患者血浆和胎盘降钙素基因相关肽含量的测定

目的：为研究降钙素相关肽在先兆子痫病生机制中的作用。方法：本文采用放免免疫测定法测定了２１例健康未妊娠妇女,２５例正常妊娠妇女（妊娠组）及２５例先兆子痫患者血浆降钙素基因相关肽水平,同时测定了妊娠期与先兆子痫组胎盘组织及胎儿血浆降钙素基因相关肽水平。结果：在妊娠组与行兆子痫组间,母体与胎儿血浆中以及胎盘组织中降钙素基因盯关肽含量均无明显变化,但平体与儿血浆含量具有明显相关性。结论：降钙素基因相关肽     

降钙素基因相关肽对大鼠心肌缺血损伤的影响

目的:观察降钙素基因相关肽对大鼠缺血心肌的保护作用。方法:用单剂量异丙肾上腺素皮下注射复制大鼠心肌缺血损伤模型,单剂量降钙素基因相关肽静脉注射治疗,2 h后采血测定血清心肌酶及血清MDA、SOD水平,同时取心肌组织匀浆测组织MDA、SOD水平,并观察心肌组织结构改变。结果:(1)异丙肾上腺素致缺血心肌损伤大鼠血清和心肌组织MDA升高、SOD下降,而CGRP治疗能逆转上述改变(P＜0.05)。(2)CGRP治疗组心肌酶CK、LDH明显低于损伤组(P＜0.05)。(3)心肌光镜、电镜结果示CGRP组细胞损伤程度明显低于损伤组(P＜0.05)。结论:CGRP对异丙肾上腺素所致大鼠缺血心肌有保护作用,抗膜脂质过氧化可能是其重要机制。     

降钙素基因相关肽（CGRP）在败血症休克中的作用

为探讨调节肽CGRP在休克中的发病学意义,本工作在结扎大鼠盲肠加穿孔的败血症休克模型上,观察了CGRP的变化及外源性CGRP对败血症休克过程的影响。结果发现,败血症休克时,血浆中CGRP显著增加(14.3±4.0 vs 5.5±1.8 Pg/ml,P<0.01)。在休克早期、晚期运用CGRP治疗(5μg/kg CGRP ⅳ)都能明显改善动物的低血压状态(分别是14.8±0.8,15.5±0.9 vs休克组10.3±1.6kPa,P<0.05),减轻心肌组织病理损伤,减少血浆中酶(LDH,CD)的漏出。同时,也可抑制休克动物血浆中AGT-Ⅱ含量的增加,提高血浆6-kcto-PGF_1α/TXB_2的比值(早期:69.1±5.3,晚期:65.8±4.1 vs休克组51.0±4.7%,P<0.05)。结果提示,CGRP可能参与败血症休克的代偿调节,适当应用CGRP治疗败血症休克是有益的。     

Changes in calcitonin gene-related peptide expression following joint immobilization in rats

Long-term immobilization by casting can occasionally cause pathologic pain states in the immobilized side. The underlying neurophysiological mechanisms of immobilization-related pain are not well understood. For this reason, we specifically examined changes of calcitonin gene-related peptide (CGRP) expression in the dorsal root ganglion (DRG), spinal dorsal horn and posterior nuclei (cuneate nuclei) in a long-term immobilization model following casting for 5 weeks. A plastic cast was wrapped around the right limb from the forearm to the forepaw to keep wrist joint at 90°of flexion. In this model, CGRP in immobilized (ipsilateral) side was distributed in larger DRG neurons compared with contralateral side, even though the number of CGRP-immunoreactive (CGRP-IR) neurons did not differ. Spinal laminae III–V, not laminae I–II in ipsilateral side showed significantly high CGRP expression relative to contralateral side. CGRP expression in cuneate nuclei was not significantly different between ipsilateral and contralateral sides. Long-term immobilization by casting may induce phenotypic changes in CGRP expression both in DRG and spinal deep layers, and these changes are partly responsible for pathological pain states in immobilized side.     

Effects of calcitonin gene-related peptide on membrane currents in mammalian cardiac myocytes

We examined the effects of calcitonin gene-related peptide (CGRP) on the membrane currents of single atrial and ventricular cells of guinea pig heart. The tightseal whole-cell voltage-clamp technique was used. In atrial cells, like isoproterenol, CGRP increased the L-type Ca channel current (I _Ca.L) in a concentration-dependent manner. Human CGRP-(8-37), a putative CGRP receptor antagonist, completely abolished the CGRP-induced increase of I _Ca.L. Although the effects of CRGP were similar to those of isoproterenol, propranolol, a -adrenergic receptor antagonist, did not affect the CGRP-induced increase of I _Ca.L. After I _Ca.L had been maximally activated by isoproterenol (2 M) or intracellular cyclic adenosine 5-monophosphate (100 M), CGRP failed to increase I _Ca.L. Acetylcholine antagonized the effects of CGRP on I _Ca.L. Unlike the effects on atrial cells, CGRP had no significant effects on the membrane currents of ventricular myocytes. Thes results indicate that CGRP increases I _Ca.L via adenylate cyclase activation by binding to specific membrane receptors in cardiac atrial myocytes. Furthermore, CGRP receptors are expressed in atrial cells but probably not in ventricular cells.     

海水浸泡伤大鼠胃黏膜和血浆中神经激肽A和降钙素基因相关肽的动态变化

目的： 观察腹腔海水浸泡伤后大鼠胃黏膜和血浆中神经激肽A（NKA）和降钙素基因相关肽（CGRP）水平的动态变化，以探讨感觉神经肽在急性胃黏膜病变中的作用。方法：32只SD大鼠随机分成正常对照组和腹腔浸泡伤组，后者又分为1 h、2 h、3 h 3组，取大鼠胃黏膜和血浆，采用酶标法和放免法测定胃黏膜和血浆中NKA和CGRP水平。结果：随着浸泡时间的延长，腹腔浸泡伤组大鼠胃黏膜NKA和CGRP水平进行性低于正常大鼠（P<0.05），而血浆NKA和CGRP水平进行性高于正常大鼠。结论：海水浸泡伤是一损伤性因素，可引起胃黏膜中NKA和CGRP水平降低、血浆中NKA和CGRP水平升高，提示NKA和CGRP等感觉神经肽在急性胃黏膜病变发生发展过程中可能有重要作用。     

血浆内皮素降钙素基因相关肽和一氧化氮在妊高征发病中的相互关系

目的:探讨内皮素-1(ET-1)、降钙素基因相关肽(CGRP)和一氧化氮(NO)在妊高征发病中的作用和相互关系。方法:采用放免法检测60例妊高征患者和30例正常妊娠妇女以及20例正常未孕妇女血中ET-1和CGRP水平。用比色法检测各组血中NO水平。结果:妊高征患者血浆ET-1水平高于正常妊娠妇女,ET-1水平越高妊高征病情越严重。中重度妊高征患者血浆CGRP和NO水平低于正常妊娠妇女,中重度妊高征患者血浆ET-1与CGRP、NO呈明显负相关。结论:ET-1和CGRP及NO可作为判断妊高征病情程度的指标,CGRP和NO在中重度妊高征患者发病中与ET-1起拮抗作用。     

The protective effects of calcitonin gene-related peptide on gastric mucosa injury of gastric ischemia reperfusion in rats

Gastric mucosa is one of the most vulnerable tissues in human and animal. However, little is known about the effects of calcitonin gene-related peptide (CGRP) on gastric mucosa injuries induced by gastric ischemia reperfusion. The purpose of the present study was to investigate the protective effects and mechanism of CGRP on gastric mucosa injury after gastric ischemia reperfusion in rats. Thirty-six healthy Wistar rats were randomly divided into CGRP-treated, sham-operated, and control groups. Twelve rats were involved in each group. These groups were further divided into 24-h and 48-h subgroups. Gastric ischemia reperfusion injury (GI-RI) rat model was established by a 30-min celiac artery occlusion by an artery clamp, followed by 24?h or 48?h of reperfusion. CGRP (1?μg/ml) at the dose of 3?μg/kg was given intraperiloneally (IP) at the beginning of reperfusion for rats in CGRP-treated group. Saline as vehicle (3?ml/kg body weight), IP, was administered at the beginning of reperfusion for rats in control group. Sham-operated animals were subjected to an operation without GI-RI. Twenty-four hours or 48?h after operation, the samples were taken out and processed for calculating stomach mucous membrane damage index according to Guth method, detecting pathological changes of gastric mucosa tissue by light microscopy and observing the expression of gastrin (Gas) and somatostatin (SST) by immunohistochemical staining. The results showed the following: (i) gastric mucosa with diffuse edema, splinter hemorrhage and erosion, numerous endothelial cells necrosis, mucosa dissociation, and infiltration of inflammatory cells were observed in both control and CGRP-treated animals, especially in the earlier period (24?h) and then gradually healing. CGRP administration could reduce the damage of gastric mucosa. The injury index of gastric mucosa was lower in CGRP-treated group as compared with that in control group (P?<?0.01). (ii) Gas expression in gastric antrum mucosa was lower in CGRP-treated group than that in control group (P?<?0.01). SST expression in gastric antrum mucosa was higher in CGRP-treated group than that in control group (P?<?0.01). It is concluded that CGRP regulated the secretion of Gas and SST and thus alleviated the damage of gastric mucosa induced by ischemia and reperfusion. CGRP might be a potential candidate for clinical therapy on modulating gastric mucosal protection and maintaining gastric mucosal integrity after ischemia and reperfusion of the stomach.     

The intramural pelvic nerves immunoreactive for calcitonin gene-related peptide in the rectum of normal and aganglionosis rat

Summary The distribution of calcitonin gene-related peptide-like immunoreactive (CGRP-LI) nerves was investigated immunohistochemically in the rectum of normal, capsaicin-treated and congenital aganglionosis rats. The rectum of the normal rat was densely supplied with both extrinsic and intrinsic nerves exhibiting CGRP-like immunoreactivity. Numerous CGRP-LI nerve fibres were seen in both the myenteric and submucous plexuses. Intrinsic CGRP-LI nerve cell bodies were sparsely found in both the ganglionated plexuses, while a large inflow of extrinsic CGRP-LI nerves was characteristically observed in the rat rectum. CGRP-like immunoreactive fibres were abundant in the intramural pelvic nerves which ascend proximally in the intermuscular zone and connect with the myenteric plexus of the rat distal bowel. As compared with CGRP-positive fibres, SP- or SK-positive fibres in the intramural pelvic nerves were far less frequent. The treatment with capsaicin in the neonatal period led to a marked depletion of CGRP-immunoreactivity in these extrinsic nerves as well as in the most terminal varicose fibres seen in the whole layers of the rectal wall. These findings suggest that the vast majority of CGRP-LI fibres in the intramural pelvic nerves are sensory in nature, and that the positive nerve fibres of extrinsic origin directly innervate each layer of the rat rectum. These CGRP-LI sensory fibres associated with the intramural pelvic nerves, may be of importance in the regulation of rectal and colonic function in normal rats. A dense innervation of CGRP-LI nerve fibres, some of which showed the varicose appearance, was also found in the rectum of congenital aganglionosis rats. Thus, it is suggested that there is a large inflow of extrinsic CGRP-LI fibres from the pelvic plexus in the affected rectum. The extrinsic CGRP-LI nerves in the aganglionic segment of the mutant rat might also be related to the regulation of rectal function, providing afferent pathways.     

Central cardiovascular effects of calcitonin gene-related peptide: interaction with noradrenaline in the nucleus tractus solitarius of rats

Summary The haemodynamic responses to microinjections of rat or human calcitonin gene-related peptide (CGRP) into the nucleus tractus solitarius (NTS) of rats were studied. 40 fmol rCGRP did not significantly modify cardiovascular parameters, but 0.2 pmol decreased blood pressure and heart rate (HR), whereas 2 pmol produced a pressor response with no effect on HR. hCGRP elicited a transient fall in blood pressure when administered at the highest dose (2 pmol), but had no effects when given at 0.2 pmol. A possible functional relationship with catecholamines was also investigated. The hypotensive response to 20 nmol noradrenaline (NA) was significantly modified by simultaneous administration of a low dose (40 fmol, ineffective alone) of rCGRP. When rCGRP (40 fmol) was coinjected simultaneously with an ineffective dose (10 pmol) of NA, a hypotensive response was observed. Our results provide evidence that rCGRP may play a role in the control of cardiovascular homeostasis in the NTS, and suggest a functional interaction between this peptide and NA.     

降钙素基因相关肽对血管平滑肌细胞心肌素表达及细胞表型改变的作用

目的:研究降钙素基因相关肽(CGRP)对血管平滑肌细胞(VSMCs)心肌素表达的影响及对细胞表型改变的调节作用。方法:取大鼠胸主动脉,以组织块贴壁培养法获得VSMCs,分为对照组、血管紧张素Ⅱ(AngⅡ)组(加入AngⅡ处理)、CGRP组(加入AngⅡ和CGRP处理)和CGRP8-37组(在AngⅡ和CGRP基础上加入CGRP8-37)。Western blot法检测VSMCs中心肌素及细胞表型标志蛋白α-平滑肌肌动蛋白(α-SMA)和骨桥蛋白(OPN)表达情况。结果:在VSMCs培养中,细胞心肌素表达水平随着培养时间延长逐渐降低,细胞培养48 h和72h时心肌素表达水平较基线水平显著降低(P0.05);而加入CGRP处理后,心肌素表达水平逐渐增加,与基线水平比较,加入CGRP培养后48 h和72 h时细胞心肌素水平显著增加(P0.05)。同时,在VSMCs培养48 h时,AngⅡ组细胞心肌素水平较对照组下降(P0.05),且α-SMA表达亦相应下降(P0.05),而OPN表达水平显著增加(P0.05);CGRP组VSMCs心肌素水平较AngⅡ组增加,伴随着α-SMA表达水平增加(P0.05),相反地OPN表达水平下降(P0.05);CGRP8-37组心肌素和α-SMA表达水平较CGRP+AngⅡ组降低(P0.05),而OPN表达较CGRP组增加(P0.05)。结论:CGRP通过促进VSMCs心肌素的表达而抑制细胞表型转换,使细胞维持收缩表型,且这一作用是CGRP通过与其受体结合后实现的。