偏头痛患者血浆一氧化氮和降钙基因相关肽含量测定及发病机制 …

目的 探讨一氧化氮（ＮＯ）和降钙素基因相关肽（ＣＧＲＰ）在偏头痛发病机制中的作用。方法 采用分光光度法和放免法，对偏头痛发作期２６例、间歇期２３例，其他头痛患者２７例及正常人２０例颈静脉（ＥＩＶ）和肘静脉（ＣＦ）血中ＮＯ和ＣＧＲＰ进行了测定。结果 偏头痛发作组ＥＪＶ和ＣＦ血中ＮＯ含量均较正常人显著升高（Ｐ均〈０．０１）；偏头痛发作组ＥＪＶ血中ＣＧＲＰ含量明显升高（Ｐ〈０．０１），而ＣＦ血中两组间无     

实验性犬SAH后CVS血浆、CSF中ET、CGRP含量动态变化及巴曲酶的保护作用研究

采用放免法动态观察了２５只实验性犬ＳＡＨ后ＣＶＳ动物模型的血浆、ＣＳＦ中ＥＴ及ＣＧＲＰ含量变化及巴曲酶的保护作用。结果：单纯注血组及巴曲酶治疗组的血浆、ＣＳＦ中ＥＴ含量较对照组明显增高（Ｐ＜０．０１），ＣＧＲＰ含量明显降低（Ｐ＜０．０１）。单纯注血组在注血后３０ｍｉｎ血浆、ＣＳＦ中ＥＴ含量开始升高，ＣＧＲＰ含量开始下降，至第７ｄＥＴ达最高值，ＣＧＲＰ达最低值。经蛛网膜下腔及静脉注入巴曲酶０．４ＢＵ／ｋｇ／ｄ组，血浆及ＣＳＦ中ＥＴ含量均较同期单纯注血组明显降低（Ｐ＜０．０１），而ＣＧＲＰ则明显升高（Ｐ＜０．０１）。提示血浆、ＣＳＦ中ＥＴ、ＣＧＲＰ失衡是ＳＡＨ后ＣＶＳ的原因之一。巴曲酶可防止ＥＴ升高和ＣＧＲＰ降低。     

偏头痛与血浆cGRP、ANF和AⅡ含量的研究

采用放射免疫分析技术对３１例偏头痛患者血浆钙基因相关肽（ｃＧＲＰ）、心房利钠多肽（ＡＮＦ）和血管紧张素Ⅱ（ＡⅡ）含量进行了研究。发现偏头痛发作期血浆ｃＧＲＰ和ＡⅡ含量显著高于间歇期（Ｐ均＜０．０１），也显著高于对照组（Ｐ均＜０．０１），血浆ＡＮＦ含量各组间无显著差异。偏头痛间歇期血浆ｃＧＲＰ、ＡＮＦ、ＡⅡ含量与对照组比较均无显著差异。偏头痛发作患者经英明格针剂注射后，血浆ｃＧＲＰ含量显著下降（Ｐ＜０．０１），而ＡＮＦ和ＡⅡ含量则无显著变化。因此，偏头痛发作与血浆ｃＧＲＰ含量增高具有重要关系。     

CGRP,ET活性应变效应与急性脑卒中关系的研究

采用放免法监测６４例急性脑卒中患者血浆、脑脊液（ＣＳＦ）中降钙素基因相关肽（ＣＧＲＰ）、内皮素（ＥＴ）含量变化。结果表明，两种物质呈负相关性同步敏感活跃。脑出血组ＣＧＲＰ升高占优势（Ｐ＜０．０１）；脑梗塞组ＥＴ升高占优势（Ｐ＜０．０１）。恢复期脑出血组ＣＧＲＰ明显下降，ＥＴ回升；脑梗塞组相反，ＥＴ显著下降，ＣＧＲＰ回升。ＣＧＲＰ、ＥＴ变化与病变部位、病灶大小、血压高低相关。提示ＣＧＲＰ、ＥＴ活性变化与血管舒缩功能失衡有其内在联系。     

降钙素基因相关肽与偏头疼关系的研究

目的 探讨降钙素基因相关肽（ＣＧＲＰ）与偏头痛发病机理的关系。方法 应用放免法对偏头痛发作期患者肘静脉血，颈外静脉血及脑脊液（ＣＳＦ）中ＣＧＲＰ含量进行测定，并与脑血管病人及正常人作对比。结果 偏头痛患者肘静脉血，颈外静脉血及ＣＳＦ中ＣＧＲＰ含量均明显高于脑血管病人及正常人组（Ｐ〈０．０１），结论 偏头痛发作与血管活性物质－ＣＧＲＰ含量变化密切相关。     

实验性犬SAH后CVS血浆,CSF中ET,CGRP含量动态变化及巴曲…

采用放免法动态观察了２５只实验性犬ＳＡＨ后ＣＶＳ动物模型的血浆，ＣＳＦ有ＥＴ及ＣＧＲＰ含量变化及巴曲酶的保护作用，结果；单纯性血组及巴曲酶治疗组的血浆，ＣＳＦ中ＥＴ含量较对照组明显增高（Ｐ〈０．０１），ＣＧＲＰ含量明显降低（Ｐ〈０．０１）。单纯注血组在注血后３０ｍｉｎ血浆，ＣＳＦ中ＥＴ含量开始升高，ＣＧＲＰ含量开始下降，至第７ｄＥＴ达最高值，ＣＧＲＰ达最代值。经蛛网膜下腔及静脉注入巴曲酶０．４ＢＵ     

高压氧治疗对急性脑梗死患者CGRP、ET含量的影响

目的：探讨高压氧（ＨＢＯ）治疗对急性脑梗死患者ＣＧＲＰ、ＥＴ含量的影响。方法：采用放射免疫方法检测ＨＢＯ加尼莫地平治疗（ＨＢＯ组）的急性脑梗死患者３０例，常规药物治疗（对照组）的急性脑梗死患者 ３５例。测定 ＨＢＯ治疗前后ＣＧＲＰ、ＥＴ的含量变化，并与对照组对比分析。结果：ＨＢＯ治疗后较治疗前ＥＴ明显降低，ＣＧＲＰ则显著升高，与对照组比差异非常显著（Ｐ＜０．０１）。ＥＴ与ＣＧＲＰ含量变化呈负相关（ｒ＝－０．２６３，Ｐ＜０．０５）。结论：ＨＢＯ治疗可使急性脑梗死患者的ＥＴ含量下降，ＣＧＲＰ含量升高，有利于急性脑梗死患者的治疗恢复。     

脑梗塞患者血浆和脑脊液中内皮素-1、降钙素基因相关肽含量的研究

用放免法检测４０例脑梗塞患者脑脊液和不同病期血浆中内皮素－１（ＥＴ－１）、降钙素基因相关肽（ＣＧＲＰ）的含量并与对照组比较。结果：脑梗塞患者脑脊液中ＥＴ－１含量无明显改变（Ｐ＞０．０５），ＣＧＲＰ含量显著降低（Ｐ＜０．０１）。发病２周内血浆ＥＴ－１含量明显高于对照组（Ｐ＜０．０５），而发病４周内ＣＧＲＰ值却显著低于对照组（Ｐ＜０．０１）。患者是否伴高血压、神经功能缺损轻重、梗塞灶大小对血浆ＥＴ－１和ＣＧＲＰ含量均无明显影响。     

重症肌无力患者若干临床问题探讨（附10例分析）

报告１０例ＭＧ病人均检测了周围血淋巴细胞计数、血清免疫球蛋白（ＩｇＧ、ＩｇＡ、ＩｇＭ）、补体Ｃ３、ＣＨ５０、Ｅ－玫瑰花结试验（ＥＲＦＴ）和淋巴细胞转换试验（ＬＴＴ），同时还测定血丙酮酸及酶谱（ＧＯＴ、ＬＤＨ、ＣＰＫ），并设３０例正常对照。ＭＧ组与对照组比较，除ＥＲＦＴ（Ｐ＜０．００１）、ＧＯＴ（Ｐ＜０．０１）、ＣＰＫ（Ｐ＜０．０１）、及ＬＤＨ（Ｐ＜０．０５）有差异外，余诸项均无统计学意义、提示一般血清免疫学或补体测定对ＭＧ诊断无特异性意义，结合文献复习对ＭＧ患者若干临床问题分别进行讨论。     

急性闭合性颅脑损伤患者血清髓鞘碱性蛋白及其抗体含量的研究

用酶联免疫吸附法（ＥＬＩＳＡ）测定３６例急性闭合性颅脑损伤（ＡＣＨＴ）患者、４０例其它神经系统疾病（ＯＮＤ）患者及３２名正常人的血清髓鞘碱性蛋白（ＭＢＰ）及其抗体（Ａｎｔｉ－ＭＢＰ）含量。结果表明：ＡＣＨＴ组患者血清ＭＢＰ含量显著高于ＯＮＤ组与正常人组（均Ｐ＜０．０１），ＡＣＨＴ患者中脑挫裂伤组和脑内血肿组血清ＭＢＰ含量较脑震荡组明显增高（均Ｐ＜０．０１）；而ＯＮＤ组与正常人组比较则无明显差异（Ｐ＞０．０５）。ＡＣＨＴ组患者血清Ａｎｔｉ－ＭＢＰ含量与ＯＮＤ组比较差别无显著性（Ｐ＞０．０５）。提示血清ＭＢＰ含量对判断颅脑损伤的病情有重要价值。     

偏头痛与感染性头痛患者血清超敏C反应蛋白与降钙素基因相关肽测定的意义及相关性

目的研究超敏C反应蛋白（hs-CRP）与降钙素基因相关肽（CGRP）在偏头痛与感染性头痛患者血清中的变化意义及相关性。方法选择39例偏头痛、38例感染性头痛患者及36例健康者,用免疫比浊法测定hs-CRP,放射免疫分析法测定血浆CGRP含量。结果 hs-CRP含量：偏头痛先兆期（3.86±1.45）mg/L、发作期（4.42±1.56）mg/L、间歇期（2.73±1.06）mg/L,感染性头痛（8.56±1.64）mg/L,均明显高于对照组（1.62±0.38）mg/L,分别P〈0.01、P〈0.05;而感染性头痛又明显高于偏头痛发作期（P〈0.01）。CGRP含量：偏头痛发作期（80.64±10.83）pg/mL,感染性头痛（67.25±9.86）pg/mL,高于对照组（59.32±7.62）pg/mL,分别P〈0.01、P〈0.05;先兆期、缓解期与正常对照组比较差异无统计学意义。相关分析发现,偏头痛发作期hs-CRP与CGRP呈正相关（r=0.3426,P〈0.05）。结论偏头痛患者hs-CRP阶段性改变,CGRP的释放与炎性标记物hs-CRP有明显相关性,hs-CRP可作为偏头痛发作各期的一种低水平炎性反应检验学指标,对感染性头痛有一定鉴别诊断意义。     

Suppressing effect of the serotonin 5HT1B/D receptor agonist rizatriptan on calcitonin gene-related peptide (CGRP) concentration in migraine attacks

Calcitonin gene-related peptide (CGRP) is one of the neuropeptides most abundant in the nervous tissue. Recent studies indicate that local cranial release of CGRP from the trigeminal nerve perivascular endings within arachnoidea plays an important role in the pathophysiology of migraine attacks and cluster headaches. Elevated CGRP levels in cranial venous blood (in the jugular vein) during an acute spontaneous migraine attack have been reported in rather few studies so far. Sumatriptan--a selective serotonin 5HT1B/D receptor agonist, highly effective in terminating migraine attacks, decreases the elevated CGRP level back to normal. The aim of our study was to determine the effect of rizatriptan (a drug from a new generation of triptans) on CGRP release in migraine attacks. In 45 patients suffering from migraine attacks with and without aura, plasma CGRP levels were assessed during an attack twice: before treatment and two hours after rizatriptan administration. In the group under study the plasma CGRP level before treatment was significantly higher than that measured two hours after rizatriptan administration. The decrease in CGRP levels was associated with subsidence of the migraine attack. There was no difference between migraine patients with and without aura. These results suggest that triptans as serotonin 5HT1B/D receptor agonists decrease CGRP plasma concentration in migraine attacks.     

The effect of melatonin on gene expression of calcitonin gene-related peptide and some proinflammatory mediators in patients with pure menstrual migraine

The neuropeptide calcitonin gene-related peptide (CGRP), a potent vasoactive and a marker of trigeminal inflammation, has been considered as an important mediator in various types of migraine such as pure menstrual migraine. Earlier studies have shown that CGRP can modulate the synthesis and release of other inflammatory factor including nitric oxide (NO) and interleukin-1beta (IL-1β) from trigeminal ganglion glial cells. Exogenous melatonin protects the tissues from inflammatory damages. The goal of this study was to determine the anti-inflammatory effects of melatonin on the CGRP expression, inducible nitric oxide synthase (iNOS) activity, NO, and IL-1β release in cultured peripheral blood mononuclear cells (PBMCs) from pure menstrual migraine patients and healthy subjects. This study was performed on 12 pure menstrual migraine patients and 12 age-and sex-matched healthy subjects. PBMCs were isolated and treated with melatonin for 12 h at pharmacological dose. Gene expression was evaluated by real-time PCR. CGRP and IL-1β proteins in culture supernatant were determined by ELISA method. iNOS activity in PBMCs was determined by colorimetric assays. Total nitrite as an indicator of NO concentrations in the culture supernatants was measured using Griess method. We found that melatonin treatment significantly decreases mRNA expression of CGRP release, NO production, and iNOS activity in the patient groups. Taken together, it appears that melatonin reduces inflammation through decreasing CGRP level and iNOS activity in the patients with migraine; however, further studies are needed in this regard.     

Increased urinary excretion of nitric oxide metabolites in longitudinally monitored migraine patients

This study evaluated a relationship between nitric oxide (NO) and migraine attacks in order to gain insight into migraine pathomechanism. The study groups consisted of 12 migraineurs and eight controls. All subjects collected morning urine samples for 40 consecutive days. Urinary NO metabolites, nitrite/nitrate (NO _x ) levels were measured with the vanadium-based assay, whilst creatinine (Cr) and neopterin were determined with high-performance liquid chromatography. The mean urinary NO _x /Cr ratio and number of NO _x peaks was significantly greater in the migraine group compared with controls ( P  = 0.01 and P  = 0.007, respectively). In the second approach, high NO _x values were re-assessed in relation to raised neopterin, a marker of systemic infection or inflammation, and were excluded. The excretion of NO _x persisted being pulsatile, and migraineurs had more peaks compared with controls ( P  = 0.01). In seven patients, NO _x peaks coincided with headache days. This was more frequent than expected by random association in four patients (Monte-Carlo simulation; odds ratios: 2.16–7.77; no overlap of 95% CI). In four patients, NO _x peaks preceded or followed headache days. Although there is a difference in the pattern of urinary NO _x excretion between control and migraine populations, the variable temporal association of NO _x peaks and headaches suggests a complex role of NO in this condition.     

癫痫患者血浆及脑脊液中一氧化氮含量的变化与临床意义

采用高效液相色谱法对37例正常对照病人和58例癫痫病人血浆及脑脊液中一氧化氮(NO)含量进行检测。结果显示:癫痫患者血浆及脑脊液中NO含量明显升高,与对照组相比有显著性差异,P均<0.01,且近期有癫痫发作者其血浆及CSF中NO含量较无发作者升高更明显,但与病程、年龄、性别及发作类型、用否抗痫药物无关。提示:NO参与了癫痫发病的病理生理过程。     

长期饮酒脑缺血大鼠血浆NPY、CGRP、ET含量的测定

目的 探讨长期饮酒对脑缺血大鼠血浆中神经肽Y(NPY)、降钙素基因相关肽(CGRP)、内皮素(ET)含量的影响。方法 选用180～200g雄性Wistar大鼠50只，分为饮水组与饮酒组，饮酒组以7．2％酒精喂养100d，制作长期饮酒模型，后将两组用线拴法制作脑缺血模型，在缺血前、缺血1h、3h、6h分别取血，用放免法测定NPY、CGRP、ET。结果 各时间段饮酒组NPY含量明显高于饮水组P％0．05，缺血3h时，两组血浆NPY含量明显升高，于6h逐渐下降；各时间段饮酒组CGRP均低于饮水组P％0．01，饮水组于缺血3h、饮酒组于缺血1h时，血浆中CGRP明显下降；饮酒组血浆ET于缺血前及缺血1h明显高于饮水组P％0．05，饮水组于缺血3h、饮酒组于缺血1h血浆ET明显升高。结论 脑梗死超早期伴有血浆NPY、CGRP、ET的动态改变，长期饮酒可加重这些变化．增加血浆中缩血管物质的含量减少舒血管物质的含量，进一步减少脑部血液供应。     

Visual evoked potential changes in migraine. Influence of migraine attack and aura

OBJECTIVE: To assess the visual evoked potential (VEP) changes in migraines with and without aura. STUDY DESIGN: A clinical study in which the VEP results of 45 migraineurs (study group) and 22 healthy volunteers (control group) were compared. Of 45 migraineurs, 29 had migraine with aura (MA) and 16 had migraine without aura (MOA), and they were examined both during and between the migraine attacks. METHODS: The patients and healthy controls underwent VEP assessment. On VEP recording, mono-ocular stimulation was performed by means of the pattern reversal check board. The latencies of N1, P1 and N2, and the N1--P1 amplitude were noted. The following comparisons were made between NI, P1 and N2 latencies and N1--P1 amplitudes of the migraine and control groups; during and between attack the VEP results of the patients with MA and MOA. RESULTS: The VEP results of the migraineurs and healthy controls were similar (P>0.05). The during attack results of MA, during and between attack results of MOA, and the results of the control group were also similar (P>0.05). N2 latency significantly elongated in patients with MA in the attack free period than it was during the attack (P=0.01), and was also longer than it was in the control group (P=0.01). CONCLUSIONS: There is involvement of the visual pathway in MA rather than MOA, and differentiation between these subtypes of the migraine disease may be performed on the basis of VEP findings manifesting by the prolongation of the N2 wave latency. This contention should be confirmed by further studies.     

The importance of cytokines, chemokines and nitric oxide in pathophysiology of migraine

The certain etiology migraine is unknown. The study was aimed at determining to the efficiency of cytokines, chemokines and nitric oxide (NO) to the pathophysiology of migraine. The levels of cytokines, chemokines and NO in serum of 25 patients with migraine during attacks and attack-free periods and 25 healthy controls were investigated. The levels of cytokines and chemokines were determined by enzyme-linked immunosorbent assay. NO concentrations were determined by a nitrate/nitrite colorimetric assay kit. In attack groups, IL-10 levels were found higher than in attack-free groups and healthy controls (p<0.05). IL-6 levels in migraine patients were significantly higher than in healthy controls. The levels of RANTES were high in attacks groups. There was an increase NO concentrations in migraine attacks. The study's results reflect that the etiology of migraine is multifactorial and probably related to immunological changes.     

Acupuncture at the San Jiao meridian affects brain stem issue G protein content in a rat migraine model

BACKGROUND: G protein is closely associated with vasomotion. Vasomotor dysfunction accompanies migraine attack. OBJECTIVE: To investigate the effects of the San Jiao meridian acupuncture on G protein content in a rat migraine model. DESIGN, TIME AND SETTING: The present randomized grouping, cellular and molecular biological level trial was performed at the Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University & Key Laboratory for Tumor Proteomics of Ministry of Health between October 2003 and June 2004. MATERIALS: Forty healthy, male, Sprague Dawley rats were included in this study. The G6805-2A elector-acupuncture apparatus was a product of Shanghai Huayi Medical Instrument Factory, China. Nitroglycerin was produced by Guangzhou Mingxing Pharmaceutical Factory, China. Antibodies against inhibitory and stimulatory G proteins were purchased from Sigma Chemical Company, USA. METHODS: All 40 rats were randomly and evenly divided into 4 groups. In the blank control group, the rats remained untouched. Rats from the normal control group were subcutaneously administered 2 mL/kg physiological saline. In the model group, migraine was induced with a subcutaneous injection of 10 mg/kg nitroglycerin (5 g/L), and the rats received no further treatment. In the acupuncture-treated group, 30 minutes after migraine induction, acupuncture was performed at the bilateral Waiguan (SJ 5) and Yifeng (SJ 17) points, with an acupuncture depth of 1 mm. Electric-stimulation parameters of 20 Hz for low frequency, 40 Hz for high frequency, and 0.5-1.0 mA for current intensity were set. Ten acupuncture sessions were applied, with 20-minute low-frequency and 20-minute high-frequency stimulation and 3 seconds of interval time. MAIN OUTCOME MEASURES: Inhibitory and stimulatory G protein contents were detected by Western blot analysis. RESULTS: At 4 hours after migraine induction, compared with the blank control and normal control groups, stimulatory G protein concentration was significantly increased, while inhibitory G protein levels were significantly decreased in the model group (P < 0.01). In the acupuncture-treated group, both stimulatory and inhibitory G protein concentrations were significantly increased following acupuncture treatment (P < 0.01 ), but stimulatory G protein levels were less and the inhibitory G protein concentrations were greater compared to the model group (P < 0.01). There was no significant difference in stimulatory and inhibitory G protein levels between the blank control and normal control groups (P > 0.05). CONCLUSION: Dysfunctional G protein signal transductions in the rat brain stem may be responsible for migraine attack. Acupuncture at the San Jiao meridian ameliorates migraines by mediating the G protein signal transduction pathway.     

Interictal levels of calcitonin gene related peptide in gingival crevicular fluid of chronic migraine patients

Calcitonin gene related peptide (CGRP) is a mediator of neurogenic inflammation playing a major role in the pathogenesis of migraine. Increases in serum CGRP have been detected previously in migraineurs and a return to baseline values regarded as successful treatment. As gingival crevicular fluid is known to originate from the serum, the aim of this study is to measure the CGRP content of gingival crevicular fluid (GCF) in chronic migraine patients and to determine whether there is a correlation between serum and GCF values of CGRP. For this study, 24 female individuals suffering from chronic migraine with aura were age-matched with 15 healthy individuals. Serum and GCF samples were obtained from both groups and enzyme linked immunosorbent assay performed to measure CGRP concentration. The level of CGRP in the serum and GCF of chronic migraine patients was 41?±?16 pg/mL and 0.25?±?0.09 pg/μg respectively while in healthy individuals CGRP levels were 29?±?8 pg/mL and 0.19?±?0.07 pg/μg. The correlation between CGRP levels of the GCF and serum was 0.88 for migraineurs and 0.81 in the controls. Only a weak positive relationship was observed between age and CGRP levels in both groups. CGRP levels were higher in migraineurs compared with controls both in serum and GCF. Furthermore there is a strong correlation between CGRP levels of the serum and GCF. The results of this study suggest that CGRP levels of GCF have potential diagnostic purposes in patients with chronic migraine.