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1.
硝酸甘油型实验性偏头痛大鼠模型建立与评价   总被引:6,自引:0,他引:6  
评价目前国内外各种偏头痛动物模型显示,硝酸甘油型偏头痛模型既具有人类偏头痛发作的相似性,又有较好的重复性、适用性及易操作性。该文对复制Wistar大鼠偏头痛动物模型所需要的硝酸甘油适当剂量进行了探索。  相似文献   

2.
目的 观察青藤碱对偏头痛模型大鼠血浆降钙素基因相关肽(CGRP)、P物质(SP)含量及脑干5-羟色胺(5-HT)表达的影响,探讨青藤碱治疗偏头痛的作用机制,为开发治疗偏头痛新药提供实验依据.方法 60只Wistar大鼠(雌雄各半)随机分为:空白对照组、模型组、舒马普坦组、青藤碱低、中、高剂量治疗组,建立硝酸甘油的动物模型.以舒马普坦为阳性对照组,用放免法测定大鼠血浆CGRP、SP含量;免疫组化SBAC法检测脑干5-HT阳性表达.同时观察大鼠的行为学变化.结果 (1)各组大鼠血浆CGRP、SP含量差异无统计学意义(P>0.05);(2)青藤碱各组和舒马普坦组脑干5-HT表达明显增多,与模型组和空白组相比较差异有统计学意义P<0.01),而青藤碱中剂量组脑干5-HT表达和舒马普坦组相比较差异无统计学意义P>0.05).(3)大鼠行为学观察显示,药物干预组对偏头痛模型大鼠行为症状随时间延长而逐渐消失.结论 (1)青藤碱对偏头痛模型大鼠具有镇痛作用,其机制可能是通过偏头痛发作时调节脑干5-HT能系统的活性,起到镇痛作用.(2)青藤碱对偏头痛模型大鼠行为症状学有改善作用.  相似文献   

3.
中药头痛宁胶囊治疗偏头痛效果较为满意,但其治疗作用途径是否由内源性阿片肽来实现尚不清楚。实验以硝酸甘油型偏头痛大鼠为模型,在基因转录和蛋白表达水平检测头痛宁胶囊对偏头痛大鼠中脑脑啡肽表达的影响。结果发现,服用头痛宁胶囊偏头痛大鼠中脑脑啡肽原mRNA水平明显上调,中脑甲硫氨酸脑啡肽和亮氨酸脑啡肽阳性细胞数目明显高于模型组。由此认为头痛宁胶囊可通过促进硝酸甘油型偏头痛大鼠中脑脑啡肽的表达,发挥其治疗偏头痛的作用。  相似文献   

4.
目的 观察青藤碱对偏头痛模型大鼠脑于c-fos、c-jun表达的影响,了解青藤碱有无治疗偏头痛的作用.方法 60只健康Wistar大鼠随机分为空白对照组、模型组、舒马普坦对照组和青藤碱低、中、高剂量治疗组.皮下注射硝酸甘油(NTG)复制实验性偏头痛动物模型,药物干预4h后断头取脑.免疫组化法检测脑干c-fos、c-jun表达水平,显微镜下计数阳性细胞数.结果 与空白对照组相比较,模型组脑干c-fos、c-jun表达明显增多,差异有显著统计学意义(P<0.01);与模型组相比较,青藤碱高、中、低剂量组和舒马普坦组脑干c-fos、c-jun表达明显减少,差异有显著统计学意义(P<0.01);与舒马普坦组相比较,青藤碱高剂量组脑干c-fos、c-jun表达无差异,无统计学意义(P>0.05).结论 青藤碱可能通过某些作用机制治疗偏头痛,阻断疼痛刺激信号传入脑干,抑制脑干c-fos、c-jun表达,减轻颅内疼痛长时程反应.  相似文献   

5.
全蝎有很强的镇痛作用,但其镇痛机制尚不明确。实验以硝酸甘油型偏头痛大鼠为模型,在基因转录和蛋白表达水平检测全蝎对偏头痛大鼠中脑脑啡肽表达的影响。结果发现,全蝎灌胃的偏头痛大鼠行为学评分明显降低,中脑脑啡肽原mRNA表达明显上调,中脑甲硫氨酸脑啡肽阳性细胞数明显增多,而亮氨酸脑啡肽阳性细胞数与偏头痛大鼠及正常大鼠无差异。由此认为全蝎可以通过上调硝酸甘油型偏头痛大鼠中脑脑啡肽的表达,减轻偏头痛的不适症状。  相似文献   

6.
目的探究光照对硝酸甘油诱导的慢性偏头痛小鼠模型行为症状学的影响。方法应用硝酸甘油诱导小鼠慢性偏头痛,观察每次给硝酸甘油后,在不同光源干预下小鼠的行为学症状。结果亮光、频闪光明显使造模后的小鼠焦虑程度加重,黑暗坏境使小鼠焦虑程度降低;随着小鼠急性偏头痛转向慢性的过程,表现焦虑程度的行为如挠头次数下降、活动度减少;慢性偏头痛引起小鼠体质量减轻。结论亮光和频闪光能加重小鼠的焦虑程度并诱导畏光行为如闭眼、缩进角落,黑暗坏境是偏头痛缓解因素;长期的慢性偏头痛会导致小鼠体质量下降,活动度下降。  相似文献   

7.
目的观察养血清脑颗粒对硝酸甘油偏头痛模型大鼠脑干三叉神经脊束核c-Fos蛋白表达变化的影响。方法共90只雄性Wistar大鼠,分别于皮下注射硝酸甘油建立偏头痛动物模型之前(预防组)、模型制备后(治疗组)接受高剂量(0.32 g/ml)或低剂量(0.16 g/ml)养血清脑颗粒治疗,行为学评价后行免疫组织化学染色检测大鼠三叉神经脊束核神经元c-Fos蛋白表达水平。结果模型组大鼠各观察时间点(30、60、180 min)三叉神经脊束核神经元c-Fos蛋白表达水平与高、低剂量治疗组之间差异无统计学意义(均P0.05);但高于高剂量预防组(P=0.031,0.000,0.000),并于制模后60和180 min时高于低剂量预防组(均P=0.000);制模后30 min时高剂量预防组大鼠三叉神经脊束核神经元c-Fos蛋白表达水平低于低剂量预防组(P=0.029)。结论预防性应用养血清脑颗粒可以显著降低三叉神经脊束核c-Fos蛋白表达水平。提示养血清脑颗粒对偏头痛的预防作用大于治疗作用,其机制可能与降低三叉神经脊束核c-Fos蛋白表达水平有关。  相似文献   

8.
目的 研究天舒胶囊对偏头痛动物模型血浆及脑组织血管活性物质及血流动力学的影响.方法 皮下注射硝酸甘油分别制作大鼠和兔偏头痛模型.给予天舒胶囊后用放免法和分光光度法测大鼠血浆一氧化氮(NO)和一氧化氮合酶(NOS)、降钙素基因相关肽(CGRP)含量;通过免疫组织化学染色观察三叉神经脊束核神经元型NOS(NOS1)和CGRP表达;用经颅多普勒检测兔颈内动脉血流速度改变.结果 模型组大鼠血浆NO、NOS和CGRP较对照组明显升高;经不同剂量天舒胶囊灌胃后大鼠血浆NO、NOS和CGRP的增加受到抑制,尤以中、高剂量组明显(P<0.05~0.01).模型组兔颈内动脉收缩期峰值流速明显下降,经中剂量天舒胶囊干预后流速下降也受到抑制 (P<0.05).免疫组织化学染色发现灌胃天舒胶囊后,偏头痛大鼠三叉神经脊束核NOS1和CGRP表达增加的程度减小(均P<0.05).结论 天舒胶囊可改善偏头痛发作时血管活性物质和神经递质水平失常,从而缓解偏头痛症状.  相似文献   

9.
目的 利用硝酸甘油实验性偏头痛大鼠模型探讨P/Q型钙离子通道在偏头痛发病机制中的作用.方法 20只sD大鼠(雌雄各半)随机分为生理盐水对照组和模型组.模型组按Tassorelli Cristina法复制偏头痛大鼠模型(每周1次,连续4次),第4次造模后分别取三叉神经节及三叉颈复合体、大脑额叶组织.RT-PCR及Western-blot法测定P/Q型钙离子通道mRNA及蛋白的表达量,同时用Fluo-3/AM荧光法测定其细胞内钙离子浓度.结果 与对照组相比,模型组大鼠三叉神经节及三叉颈复合体(mRNA:0.472 36±0.049 54;蛋白:0.337 25±0.035 93)和大脑额叶组织(mRNA:0.547 45±0.044 39;蛋白:0.402 13±0.029 83)中的P/Q型钙离子通道在mRNA及蛋白水平均表达上调(t=2.6697、3.1993、3.4398、3.7661,P<0.05),同时细胞内钙离子浓度也明显高于对照组(P<0.05).结论 P/Q型钙离子通道可能通过其表达量的上调参与了偏头痛的发生发展过程.  相似文献   

10.
目的观察罗格列酮对硝酸甘油诱导大鼠偏头痛模型的保护作用。方法 48只雄性SD大鼠随机分为模型组、罗格列酮组和对照组。模型组(按Tassorelli法皮下注射硝酸甘油复制大鼠偏头痛模型),罗格列酮组(于造模后30 min腹腔注射罗格列酮),对照组(不造模,皮下注射生理盐水)。观察大鼠行为学变化,采用免疫组化和Western blot法观察三叉神经颈复合体过氧化物酶体增殖物激活受体γ(PPARγ)及白介素-6(IL-6)、细胞间黏附分子-1(ICAM-1)、基质金属蛋白酶-9(MMP-9)表达。结果对照组三叉神经颈复合体中PPARγ为弱阳性表达,模型组为阳性表达,罗格列酮组为强阳性表达。模型组IL-6、ICAM-1和MMP-9表达高于对照组(P0.05)。罗格列酮组大鼠耳发红、肢频繁挠头、爬笼次数增多、烦躁不安等症状减轻,IL-6、ICAM-1、MMP-9表达较模型组明显下降(P0.05)。结论偏头痛时PPARγ表达增强;罗格列酮可通过活化PPARγ,下调IL-6、ICAM-1、MMP-9对偏头痛具有一定的保护作用。  相似文献   

11.
目的 探讨神经调节蛋白(neuregulin,NRG)/表皮生长因子受体(epidermal growth factor receptor,ErbB)通路在偏头痛大鼠模型中的作用。方法 将Wistar大鼠随机分为对照组、模型组、空载(空慢病毒载体)组、NRG沉默(含NRG基因干扰片段的慢病毒载体)组、NRG1(0.01 mg/kg)组,每组各12只; 除对照组外,其余各组制备偏头痛大鼠模型,观察大鼠行为学表现,记录一段时间内大鼠挠头次数、爬笼次数; 测定各组大鼠机械性刺激及温度痛阈; 用酶联免疫吸附实验(Enzyme linked immunosorbent assay,ELISA)检测各组大鼠血清肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α),白介素-6(Interleukin-6,IL-6)水平; 免疫印迹实验检测各组大鼠脑组织NRG/ErbB通路相关蛋白表达水平。结果 与对照组比较,模型组、空载组大鼠挠头次数、爬笼次数、血清TNF-α及IL-6水平明显增高,机械性刺激痛阈值、热刺激潜伏期、脑组织NRG/ErbB通路相关蛋白NRG表达水平及ErbB/磷酸化表皮生长因子受体(phospho-epidermal growth factor receptor,p-ErbB)明显降低(P<0.05)。与模型组比较,空载组大鼠各指标水平无明显变化(P>0.05); NRG沉默组大鼠挠头次数、爬笼次数、血清TNF-α及IL-6水平增高,机械性刺激痛阈值、热刺激潜伏期、脑组织NRG/ErbB通路相关蛋白NRG表达水平及ErbB/p-ErbB降低(P<0.05); NRG1组大鼠挠头次数、爬笼次数、血清TNF-α及IL-6水平降低,机械性刺激痛阈值、热刺激潜伏期、脑组织NRG/ErbB通路相关蛋白ErbB/p-ErbB增高(P<0.05),NRG表达水平无明显变化(P>0.05)。结论 NRG/ErbB通路可调控大鼠偏头痛,上调该通路可减轻其头痛。  相似文献   

12.
Administration of nitroglycerin (NTG) to rats induces a hyperalgesic condition and neuronal activation of central structures involved in migraine pain. In order to identify therapeutic strategies for migraine pain, we evaluated the anti-nociceptive activity of Andrographis Paniculata (AP), a herbaceous plant, in the hyperalgesia induced by NTG administration in the formalin test. We also analyzed mRNA expression of cytokines in specific brain areas after AP treatment. Male Sprague-Dawley rats were pre-treated with AP extract 30 minutes before NTG or vehicle injection. The data show that AP extract significantly reduced NTG-induced hyperalgesia in phase II of the test, 4 hours after NTG injection. In addition, AP extract reduced IL-6 mRNA expression in the medulla and mesencephalon and also mRNA levels of TNF-alpha in the mesencephalic region. These findings suggest that AP extract may be a potential therapeutic approach in the treatment of general pain, and possibly of migraine.  相似文献   

13.
Rizatriptan is a selective 5-HT(1B/1D) receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This randomized double- blind crossover outpatient study assessed the preference for 1 rizatriptan 10 mg tablet to 2 ergotamine 1 mg/caffeine 100 mg tablets in 439 patients treating a single migraine attack with each therapy. Of patients expressing a preference (89.1%), more than twice as many preferred rizatriptan to ergotamine/caffeine (69.9 vs. 30.1%, p < or = 0.001). Faster relief of headache was the most important reason for preference, cited by 67.3% of patients preferring rizatriptan and 54.2% of patients who preferred ergotamine/caffeine. The co-primary endpoint of being pain free at 2 h was also in favor of rizatriptan. Forty-nine percent of patients were pain free 2 h after rizatriptan, compared with 24.3% treated with ergotamine/caffeine (p < or = 0.001), rizatriptan being superior within 1 h of treatment. Headache relief at 2 h was 75.9% for rizatriptan and 47.3% for ergotamine/caffeine (p < or = 0.001), with rizatriptan being superior to ergotamine/caffeine within 30 min of dosing. Almost 36% of patients taking rizatriptan were pain free at 2 h and had no recurrence or need for additional medication within 24 h, compared to 20% of patients on ergotamine/caffeine (p < or = 0.001). Rizatriptan was also superior to ergotamine/caffeine in the proportions of patients with no nausea, vomiting, phonophobia or photophobia and for patients with normal function 2 h after drug intake (p < or = 0.001). More patients were (completely, very or somewhat) satisfied 2 h after treatment with rizatriptan (69.8%) than at 2 h after treatment with ergotamine/caffeine (38.6%, p < or = 0.001). Recurrence rates were 31.4% with rizatriptan and 15.3% with ergotamine/caffeine. Both active treatments were well tolerated. The most common adverse events (incidence > or = 5% in one group) after rizatriptan and ergotamine/caffeine, respectively, were dizziness (6.7 and 5.3%), nausea (4.2 and 8.5%) and somnolence (5.5 and 2.3%).  相似文献   

14.
目的通过对硝酸甘油偏头痛模型大鼠侧脑室注射腺苷A1受体激动剂(R-phenylisopropyl-adenosine,R-PIA),探讨腺苷在偏头痛中的作用及机制。方法观察各组大鼠不同时间段内挠头、爬笼次数及心率变化,采用Elisa、免疫组织化学法、Western blot技术检测血液、三叉神经节(trigeminal ganglion,TG)、三叉神经脊束核尾核(spinal trigeminal nucleus caudalis,TNC)处降钙素基因相关肽(calcitonin gene-related peptide,CGRP)的表达。结果(1)与模型组相比,治疗组大鼠挠头、爬笼次数均减少并呈剂量依赖性(P0.05),且大鼠心率没有明显变化;(2)治疗组大鼠血液、TG、TNC部位CGRP的表达较模型组均降低(P0.05)。结论激活的腺苷A1受体能够通过抑制神经源性炎症反应及痛觉传导,从而抑制三叉神经血管系统的激活及痛觉敏化,对偏头痛产生镇痛作用。  相似文献   

15.
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.  相似文献   

16.
In this randomized, double-blind, crossover clinical trial, adult patients treated two migraine attacks: one with almotriptan 12.5 mg and the other with ergotamine 2 mg plus caffeine 200 mg. Treatment with almotriptan was associated with a significantly greater proportion of patients achieving 2-h pain free (20.9% vs. 13.7%; P  < 0.05) and 2-h pain relief (57.7% vs. 44.5%; P  < 0.01) compared with ergotamine plus caffeine therapy; significant differences were not seen at 1 h. Rates for sustained pain free and sustained pain free plus no adverse events (AEs) also were significantly greater after almotriptan treatment than after the use of ergotamine plus caffeine ( P  < 0.05). Almotriptan was associated with a significantly lower rate of photophobia at 90 min ( P  < 0.05), phonophobia at 60, 90, and 120 min ( P  < 0.05 to <0.01), and nausea and vomiting at 90 and 120 min ( P  < 0.01) compared with ergotamine plus caffeine. A significantly greater proportion of patients were more satisfied with almotriptan than with ergotamine plus caffeine ( P  < 0.05). Sixteen patients reported adverse events during almotriptan treatment and 27 patients reported AEs during the ergotamine plus caffeine therapy. Most AEs were mild-to-moderate and did not result in treatment-related discontinuations. In conclusion, almotriptan was associated with significantly greater efficacy for treating migraine compared with ergotamine plus caffeine, was generally well tolerated and was associated with greater rate of treatment satisfaction.  相似文献   

17.
Cluster headache is a rare headache entity that predominantly occurs in younger males. The clinical features are characterized by sudden attacks of unilateral excruciating pain localized periorbitally, associated with ipsilateral autonomic symptoms. The attacks occur in periods: clusters. The pathophysiology is still unknown. Such vasodilating substances as histamine, nitroglycerin and alcohol may provoke attacks. These substances may be used as diagnostic tests, but the interpretation of a negative result must be careful, as the attacks can not be induced in a refractory period after spontaneous occurrence, or at the beginning and end of cluster periods. As symptomatic treatment, ergotamine is the drug of first choice. High attack frequency may lead to overconsumption with ergotisme and further increased frequency. In such cases and for nocturnal attacks, oxygen inhalations represent an alternative. As prophylactic treatment ergotamine, methysergide, lithium and prednisone have proved efficacious. Most patients benefit from such treatment and may become virtually free from attacks. It is, therefore, important to differentiate this headache entity from classical migraine, common migraine and trigeminal neuralgia.  相似文献   

18.
目的探讨基质金属蛋白酶-9(MMP-9)在偏头痛大鼠模型中的表达情况。方法 48只雄性SD大鼠随机分为正常对照组、阴性对照组和模型组,每组16只。正常对照组不作处理,模型组采用皮下注射硝酸甘油法制作大鼠偏头痛模型,阴性对照组注射生理盐水。应用免疫组化技术及Western blot,分别观察各组大鼠硬脑膜、三叉神经节及三叉神经颈复合体MMP-9蛋白的表达情况。结果 MMP-9在各组大鼠中均有不同程度表达,模型组中MMP-9表达明显高于阴性对照组及正常对照组(P〈0.05)。结论 MMP-9在偏头痛大鼠模型中表达增强,其可能在偏头痛发病机制中发挥重要的作用。  相似文献   

19.
The effects of ergotamine and dihydroergotamine on cerebral blood flow was investigated 4 hours after i.v. injection as these drugs might be of importance for migraine treatment. Eight normal male volunteers (not suffering from migraine) received 0.5 mg ergotamine and 1 mg dihydroergotamine i.v. Cerebral blood flow was measured by the xenon-133 inhalation method and single-photon-emission computerized tomography before and after intravenous acetazolamide administration (1 g). Cerebral blood flow was measured before and 4 hours after ergotamine and dihydroergotamine administration. Strain-gauge measurements of toe-arm systolic gradients were used to monitor the effect of the drug on leg arteries. Mean hemispheric and regional cerebral blood flow was unchanged after either drug (mean +/- SEM, ml/100 g/min): for ergotamine, 57 +/- 3 before and 57 +/- 3 at 4 hours; for dihydroergotamine, 54 +/- 2 before and 55 +/- 2 at 4 hours. The acetazolamide response was unchanged as well. Only ergotamine decreased the toe-arm systolic gradient significantly (22 mm Hg at maximum after 240 minutes; p less than 0.02). Thus, our study did not support the belief that ergot alkaloids should be withheld from patients during attacks of classic migraine, but this has to be investigated further. The discrepancy in the peripheral effects of ergotamine and dihydroergotamine might also be of clinical importance.  相似文献   

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