Intracerebroventricular administration of human calcitonin and human calcitonin gene-related peptide inhibits meal-stimulated gastric acid secretion in the dog

This study was designed to assess the central nervous system actions of human calcitonin (hCalc) and human calcitonin gene-related peptide (hCGRP) on meal-stimulated gastric acid secretion in awake beagle dogs. hCalc (0.1–1.0 nmol/kg) and hCGRP (0.01–1.0 nmol/kg) injected into the third cerebral ventricle significantly inhibited gastric acid secretion stimulated by an 8% peptone meal. hCGRP was ten times more potent than hCalc in inhibiting gastric secretion. Neither hCalc nor hCGRP significantly altered plasma gastrin concentrations compared to control values. Truncal vagotomy did not prevent the gastric inhibitory actions of hCalc and hCGRP. Ganglionic blockade with chlorisondamine completely abolished the gastric inhibitory action of hCalc but had no effect on gastric acid inhibition induced by hCGRP. The results of this study indicate that intracerebroventricular administration of hCalc and hCGRP inhibits meal-stimulated gastric acid secretion in awake dogs. Inhibition of gastric acid secretion by hCalc and hCGRP in the dog is not mediated by inhibition of gastrin release or by the vagus nerves. Human Calc but not human CGRP appears to inhibit meal-stimulated gastric acid secretion in the dog by activation of the autonomic (sympathetic) nervous system.     

老年非杓型高血压病患者内皮素和降钙素基因相关肽含量变化及氨氯地平对其影响

探讨老年非杓型高血压病(EH)患者内皮素(ET)和降钙素基因相关肽(CGRP)含量变化及氨氯地平对其影响。方法观察氨氯地平治疗老年非杓型EH患者疗效及其治疗前后ET和CgRP含量变化。结果老年非杓型EH患者血浆ET水平明显高于老年杓型EH患者,而CGRP则明显降低;氨氯地平使老年非杓型EH患者白昼及夜间血压下降,治疗后老年非杓型EH患者血浆ET水平降低,而CGRP明显升高。结论ET及CGRP参与了老年非杓型EH的病理过程,氨氯地平是一种治疗老年非杓型EH患者有效药物,能纠正老年非杓型EH患者ET与CGRP之间的失衡。     

降钙素基因相关肽的血液动力学作用及其机理

静脉注射降钙素基因相关肽（ＣＧＲＰ），可使麻醉大鼠血压明显下降，在注射后１ｍｉｎ出现作用，５ｍｉｎ最明显（平均动脉压下降１５．５％），１０ｍｉｎ后恢复。在用药后心率最快时增加９．４％，持续３０ｍｉｎ，左室收缩压峰值和左室压上升最大速度分别增加１０％和１５％。ＣＧＲＰ的降压作用不能被阿托品阻断，且心率加快，心肌收缩性增强。预先用利血平阻断交感神经后再注射ＣＧＲＰ，心率无变化，平均动脉压、左室收缩压峰值、左室压上升最大速度均显著降低，且作用持续时间长。结果表明，ＣＧＲＰ的作用与交感神经的调控有密切关系．它的正性变力和变时的作用可能是通过交感神经释放递质引起的。     

高原急性重症脑功能损伤血浆肾上腺髓质素和降钙素基因相关肽测定及意义

目的研究高原急性重症脑功能损伤患者血浆肾上腺髓质素(ADM)和降钙素基因相关肽(CGRP)的变化并探讨其作用及临床意义。方法测定35例高原急性重症脑功能损伤患者(脑功能损伤组)发病第12、、3天血浆ADM、CGRP水平,同时测定20例高原健康体检者(高原对照组)、20例平原健康体检者(平原对照组)血浆ADM、CGRP水平。结果脑功能损伤组患者血浆ADM、CGRP发病3天内的水平均高于高原对照组及平原对照组(P<0.05),而发病3天之间患者的ADM、CGRP水平无明显差异(P>0.05);高原对照组血浆ADM、CGRP均高于平原对照组(P<0.05)。脑功能损伤组血浆ADM与CGRP之间呈显著正相关(P<0.05),大脑中动脉收缩期流速(SV)与发病第1天血浆ADM、CGRP呈负相关(P<0.05)。死亡病例发病第1天血浆ADM、CGRP均高于非死亡病例(P<0.05)。结论ADM和CGRP参与了急性重症脑功能损伤的发生发展过程,对损伤时脑组织起代偿性保护作用;血浆ADM、CGRP值亦可间接反映脑损伤程度。     

肌钙蛋白T与降钙素基因相关肽对急性冠状动脉综合征患者危险分层及预后评估的价值

目的　探讨肌钙蛋白T(cTnT)与降钙素基因相关肽 (CGRP)对急性冠状动脉综合征 (ACS)患者危险分层及预后评估的价值。方法　选择ACS患者 15 8例 ,其中ST段抬高心肌梗死 (STEMI) 72例 ,非ST段抬高心肌梗死(NSTEMI) 2 3例 ,不稳定型心绞痛 (UA) 6 3例 ,入院后立即抽取肘静脉血采用ELISA法测定cTnT和CGRP水平 ,并观察患者住院期间和随访 6个月期间主要心血管事件 (MACE)。结果　NSTEMI组与STEMI组相比 ,cTnT及CGRP水平无显著性差异 ,但NSTEMI组CGRP水平高于STEMI组 ,cTnT水平低于STEMI组。与STEMI组相比 ,UA组患者cTnT水平明显降低 (P <0 .0 5 ) ,而CGRP水平显著增高 (P <0 .0 5 )。陈旧心肌梗死、左心室射血分数、cTnT及CGRP水平是ACS患者MACE发生的独立预测因子。结论　cTnT及CGRP水平在NSTEMI组与STEMI组相似 ,在心绞痛组cTnT亦有轻度增高 ;心肌梗死较心绞痛患者发病时CGRP水平低 ;cTnT及CGRP水平是ACS患者MACE发生的独立预测因子。     

Recent advances in targeting calcitonin gene-related peptide for the treatment of menstrual migraine: A narrative review

Menstrual migraine (MM) has a longer duration and higher drug resistance than non-perimenstrual migraine. Calcitonin gene-related peptide (CGRP) and CGRP receptors are expressed in the peripheral and central nervous systems throughout the trigeminovascular system. The CGRP/CGRP receptor axis plays an important role in sensory physiology and pharmacology. CGRP receptor antagonists and anti-CGRP monoclonal antibodies (mAbs) have shown consistent efficacy and tolerability in the prevention of chronic or episodic migraine and are now approved for clinical use. However, few studies have reported the use of these drugs in MM, and no specific treatment for MM has been approved. This review aimed to shed light on the recent advances in targeting calcitonin gene-related peptides for the treatment of menstrual migraines in PubMed. In this review, we first discuss the axis of the CGRP/CGRP receptor. We then discuss the role of CGRP receptor antagonists and anti-CGRP mAbs in MM treatment. Finally, we discuss the role of the combination of anti-CGRP mAbs and CGRP receptor antagonists in migraine treatment and the drugs that inhibit CGRP release. Altogether, the anti-CGRP mAbs or CGRP receptor antagonists showed good efficacy and safety in the treatment of MM.     

急性胰朱炎胃肠激素变化的初步研究

目的 观察急性胰腺炎（AP）患者血浆内皮素（ET）、钙基因相关肽（CGRP）、血清胃泌素（GAS）的变化,并探讨这三种胃肠激素在AP发病机制中的作用及其临床意义。方法 应用放射免疫法测定29例AP中患者治疗前（A组）、治疗后（B组）及22例健康人（C组）血浆ET、CGRP及血清GAS水平,并进行组间对照。结果 A组血浆ET、CGRP、ET／CGRP、血清GAS水平与B组或C组比较,显著升高（P＜0．05或＜0．01）。B组三种激素ET／CGRP与C组比较无明显差异（P＞0．05）。结论 血浆ET、CGRP、血清GAS在AP时增高,测定血液ET、CGRP及GAS对于AP有相当重要的临床意义。     

降钙素基因相关肽对犬冠脉流量及冠状动脉的作用

本研究通过整体及离体灌流实验观察到重庆冠脉狭窄时，犬冠脉流量（ＣＢＦ），平均动脉压（ＭＡＰ）明显减小，而心率（ＨＲ）则增加。狭窄３０ｍｉｎ后由冠状动脉注射降钙素基因相关肽（ＣＧＲＰ）０．３μｇ／ｋｇ后，ＣＢＦ、ＭＡＰ和ＨＲ可恢复正常水平。同时，缺血犬的离体冠状动脉对ＣＧＲＰ的反应也出现改变。大冠脉舒张反应明显降低，而小冠脉的舒张反应与正常相比，无明显改变，这可能与缺血后大冠脉的内皮细胞容易损伤有关。同时也提示:急性心肌缺血时，冠脉流量的减少，主要由于小冠状动脉收缩所致。     

降钙素基因相关肽和内皮素在充血性心力衰竭中的作用

采用同位素放射免疫法同时检测30例充血性心力衰竭（CHF）患者的血浆降钙素基因相关肽（CGRP）和内皮素（ET）浓度，求出ET／CGRP比值，并与30例健康人对照，结果显示CHF患者血浆CGRP和ET浓度以及ET／CGRP比值较对照组明显增高（P＜0．05和P＜0．01）。提示在CHF时血浆CGRP和ET浓度均增高，且失去ET和CGRP的正常平衡，这对CHF的防治可能具有重要意义。     

CGRP在大鼠胃痛觉过敏形成机制中的作用

目的:探索降钙素基因相关肽(CGRP)相关的干预措施对胃痛觉过敏的影响,了解CGRP在胃痛觉过敏形成过程中发挥的作用．方法:成年SD古大鼠,均植入胃内气囊．观察伤害性扩张或CGRP iv对大鼠疼痛阈值的影响:观察由上述措施诱发内脏过敏的大鼠在给予CGRP受体特异性拮抗剂hCGRP8-37后疼痛阈值的变化:观察不同剂量CGRP和hCGRP8-37对疼痛阈值的影响．结果:CGRP iv后胃疼痛阈值为11．7±2．6 mmHg,对照组疼痛阈值为19．2±2．0 mmHg,生理盐水对照组则为18．3±2．5 mmHg,实验组与其他两组比较尸均<0．05．CGRP使大鼠的疼痛阈值降低．hCGRP8-37能逆转伤害性扩张和CGRP引起的内脏敏感性增高,该作用呈剂量依赖性(r=0．821,P<0．01)．结论:胃扩张刺激能引起胃敏感性增高,在此过程中CGRP具有重要的作用．     

急性肝衰竭大鼠血浆神经降压素和降钙素基因相关肽水平的变化

目的探讨急性肝衰竭(ALF)大鼠血浆神经降压素(NT)和降钙素基因相关肽(CGRP)含量的变化。方法采用硫代乙酰胺制备ALF大鼠模型。采用RIA法测定血浆NT和CGRP含量。结果模型组大鼠血浆NT和CGRP含量明显升高,与正常对照组比,差异有统计学意义(P0.01);模型组大鼠分别于造模后12h、24h、36h和48h,肝性脑病逐渐进展,血浆NT和CGRP含量也呈进行性升高。结论测定血浆NT和CGRP含量可作为判断肝性脑病早期诊断的指标之一,其含量的变化对肝性脑病严重程度的判断有重要的参考价值。     

肠易激综合征血清中降钙素基因相关肽的变化

目的探讨降钙素基因相关肽(CGRP)在肠易激综合征(IBS)中的变化,为进一步探讨其在IBS中的作用提供证据。方法 SPF级大鼠30只,随机分为3组:模型组大鼠以0.85 mL含三硝基苯磺酸(TNBS)的50%乙醇灌肠1次诱发远端结肠炎,对照组仅以等体积的生理盐水灌肠,正常组不作处理。正常饲养30 d后处死。造模前后均以腹部回撤反射(AWR)测定内脏感觉阈值用以评价模型。造模成功后行心脏取血,以ELISA试剂盒测定血清中CGRP浓度。结果 TNBS灌肠法复制模型成功,腹部回撤反射内脏感觉阈值测定模型组造模后内脏感觉阈值较造模前及正常组下降(P<0.05)。模型组血中CGRP浓度较对照组及正常组明显升高(P<0.05),对照组较正常组中CGRP浓度也有升高但差异无统计学意义(P>0.05)。结论模型组血清中CGRP浓度升高,可能在IBS的发生中起着一定作用。     

降钙素基因相关肽与心血管病关系研究进展

降钙素基因相关肽是一种由降钙索基因表达的舒血管活性多肽,广泛分布于神经、心血管系统,具有强大的扩张血管、降低血压及正性肌力作用,在冠心病、高血压、心力衰竭、心律失常等疾病发生和防治以及相关药物开发上具有重要意义。     

Plasma concentrations of calcitonin gene-related peptide increase during haemodialysis: relation to blood pressure

The authors measured the plasma levels of calcitonin gene-related peptide (CGRP), the most potent vasodilatator known, during sequential ultrafiltration and haemodialysis in 12 patients using a radio-immunoassay method. Mean plasma levels of CGRP were 70.3 +/- 16.5 (mean +/- SE) pmol l-1 at the start of treatment, it increased to 85.3 +/- 17.6 pmol l-1 during ultrafiltration and to 114.5 +/- 25.3 pmol l-1 during dialysis. Systolic blood pressure decreased during haemodialysis. Plasma levels of CGRP were negatively correlated to systolic blood pressure before and at the end of dialysis, and changes in plasma levels of CGRP were strongly correlated to changes in systolic blood pressure. The increase in CGRP levels was not correlated to the fluid removal, toxin removal or changes in osmolality. The increase in plasma levels of CGRP observed during dialysis may be an important cause of dialysis induced vasodilatation and fall in blood pressure.     

降钙素基因相关肽在哮喘患者气道中的表达

目的　探讨降钙素基因相关肽(CGRP)在哮喘患者气道中的表达。方法　收集轻度持续哮喘患者,通过纤支镜于右中叶嵴取活检,用S P免疫组化法检测CGRP的表达。结果　10例轻度持续哮喘患者的气道表现为黏膜上皮脱落,嗜酸细胞浸润,在黏膜下、大血管周围可见丝状、条状、串珠状或簇状CGRP表达,阳性占区域比( 0. 1286±0. 0271 )和阳性综合分析( 0. 1299±0. 0188),与对照组比较(0. 0108±0. 0013, 0. 0124±0. 0041),差异具有显著性(P<0. 01)。结论　轻度持续哮喘患者气道CGRP高表达。     

The effect of calcitonin gene-related peptide on healing of intestinal anastomosis in rats with experimental obstructive jaundice

Purpose

Intestinal anastomotic healing is a complex procedure in which several mediators and cytokines play roles. Calcitonin gene-related peptide is an important neuropeptide in inflammation. In this study we aimed to investigate the effect of calcitonin gene-related peptide on healing of intestinal anastomosis in rats with obstructive jaundice.

Materials and methods

Obstructive jaundice was induced in rats by the ligation and division of the common bile duct. Four days after the operation, intestinal anastomosis was performed, and either calcitonin gene-related peptide or 0.9% NaCl was administered intraperitoneally to these jaundiced rats and controls. The concentrations of serum tumor necrosis factor-α (TNF-α) and triglyceride levels of all rats were measured, and healing of the anastomosis was evaluated by measuring the bursting pressure and hydroxyproline content on the 7th postoperative day.

Results

Calcitonin gene-related peptide was found to have positive effects on healing of the anastomosis by inhibiting the effects of TNF-α and increasing the bursting pressure and hydroxyproline content of the anastomosis.

Conclusion

Calcitonin gene-related peptide increases anastomotic wound healing in experimental anastomosis in the presence of obstructive jaundice in rats.     

功能性消化不良胃机械感觉过敏和降钙素基因相关肽的关系

目的　探讨胃黏膜中降钙素基因相关肽 (CGRP)在胃机械感觉过敏形成机制中的作用。方法　 15例健康志愿者和 2 3例FD患者参与试验。电子恒压器测定所有受试者胃机械感觉阈值 ,根据阈值不同 ,将FD患者分为胃机械感觉正常组和胃机械感觉过敏组。利用RT PCR半定量分析受试者胃黏膜中α CGRPmRNA水平 ,比较各组间差异 ,探讨α CGRPmRNA的含量与胃机械感觉阈值之间的相关性。结果　用压力表示胃机械感觉阈值时 ,FD患者的初次感觉阈值、不适阈值、疼痛阈值和最大耐受阈值均明显低于健康志愿者 (P <0 .0 1) ,而当用容积表示胃机械感觉阈值时 ,尽管FD患者的各种阈值均低于健康志愿者 ,但除初次感觉阈值外 (P <0 .0 5 ) ,其他阈值间的差异无显著性 (P >0 .0 5 )。根据初次感觉阈值 ,35 %的FD存在胃机械感觉过敏 ,且其胃黏膜中α CGRPmRNA的表达明显高于胃机械感觉正常的FD和健康志愿者 (P <0 .0 5 ) ,而胃机械感觉正常的FD和健康志愿者的α CGRPmRNA表达没有差异 (P >0 .0 5 )。FD患者胃黏膜中α CGRPmRNA的水平与其感觉阈值呈负相关。结论　部分FD存在胃机械感觉过敏 ,胃机械感觉过敏的患者胃黏膜中α CGRPmRNA表达异常增高 ,且其含量与胃机械感觉阈值呈负相关。     

高血压病患者血浆降钙素基因相关肽和内皮素浓度的变化

目的 :探讨血浆降钙素基因相关肽 （CGRP）和内皮素 （ET）与高血压病之间关系。方法 :放射免疫方法检测 2 5例正常人和 36例高血压病患者降压治疗前后血浆 CGRP和 ET浓度 ,同时测量高血压病患者血压。结果 :1高血压病患者血浆 CGRP浓度低于正常人 ,与平均动脉压呈负相关 ;ET浓度高于正常人 ,与平均动脉压呈正相关。2有效降压治疗后 ,高血压病患者血浆 CGRP浓度回升 ,ET浓度下降 ,CGRP/ ET比值明显升高。结论 :血浆 CGRP和ET浓度失衡可能是高血压病发生的重要原因之一 ;有效降血压可能与 CGRP和 ET的变化有关。     

Plasma calcitonin gene-related peptide decreases in chronic congestive heart failure.

To investigate the role of calcitonin gene-related peptide (CGRP) in cardiac failure, a sensitive and specific radioimmunoassay was developed to study plasma levels of CGRP in 37 normal subjects and 41 patients with heart failure (HF). The mean plasma levels of CGRP were 294.3 pg.ml-1 (SEM: 41.4) in normal subjects and 121.2 pg.ml-1 (SEM: 21.2) in HF patients. The significant decrease observed in HF patients suggests that CGRP is involved in the pathogenesis of heart failure via a direct effect or via modulation of sympathetic nervous activity.