本文選題：偏頭痛 + 左乙拉西坦��； 參考：《山西醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:將SD(Sprague Dawley)大鼠給予左乙拉西坦(LEV)灌胃,觀察該藥對(duì)硝酸甘油所致偏頭痛大鼠模型在行為表現(xiàn)方面的影響以及高頸髓谷氨酸能和GABA能中間神經(jīng)元的變化,探討LEV在偏頭痛方面的防治作用,以及可能的作用機(jī)制。方法:1.將24只健康雄性SD大鼠普通喂養(yǎng)一周,采用分層隨機(jī)法,將其分成假模型組(6只)和模型組(18只)。采取皮下注射硝酸甘油(NTG)的方法,造實(shí)驗(yàn)性偏頭痛大鼠模型,假模型組大鼠給予皮下生理鹽水。造模成功后采用隨機(jī)方法將模型組中大鼠分為模型對(duì)照組(6只)、低劑量干預(yù)組(6只)及高劑量干預(yù)組(6只)。假模型組:生理鹽水灌胃,1次/日,連續(xù)1周,待末次灌胃后,進(jìn)行皮下注入生理鹽水。模型對(duì)照組:生理鹽水灌胃,1次/日,連續(xù)1周,待末次灌胃后,進(jìn)行皮下注入硝酸甘油,再次造模。低劑量干預(yù)組:左乙拉西坦100 mg/kg灌胃,1次/日,連續(xù)1周,待末次灌胃后,進(jìn)行皮下注入硝酸甘油,再次造模。高劑量干預(yù)組:左乙拉西坦200 mg/kg灌胃,1次/日,連續(xù)1周,待末次灌胃后,進(jìn)行皮下注入硝酸甘油,再次造模。2.造模成功后密切觀察每只大鼠在行為學(xué)方面的改變。每半個(gè)小時(shí)作為一個(gè)觀察時(shí)間單元,采取持續(xù)時(shí)間分段計(jì)數(shù)的方式觀察90min內(nèi)各個(gè)分段時(shí)間的大鼠撓頭、爬籠和甩頭的次數(shù)。3.復(fù)制偏頭痛模型3h后,給予腹腔注射麻醉,進(jìn)行甲醛灌注,取頸髓1-2。用免疫組化方法對(duì)谷氨酸(Glu)和γ-氨基丁酸(GABA)染色,然后用光學(xué)顯微鏡觀察谷氨酸和GABA免疫陽性細(xì)胞的數(shù)目,并在同側(cè)脊髓后角部位隨機(jī)觀察5個(gè)高倍視野,依次記錄陽性細(xì)胞數(shù)目。結(jié)果:1.行為學(xué)變化:與假模型組對(duì)照,其余各組大鼠的撓頭次數(shù)、爬籠次數(shù)和甩頭次數(shù)均呈現(xiàn)明顯增加(P0.05)。與模型對(duì)照組比較,藥物干預(yù)組大鼠撓頭次數(shù)、爬籠次數(shù)和甩頭次數(shù)均隨著給藥劑量的升高而降低。2.谷氨酸和GABA免疫陽性細(xì)胞數(shù)目:與假模型組比較,其余各組的谷氨酸免疫陽性細(xì)胞數(shù)目顯著增多(P0.05),GABA免疫陽性細(xì)胞數(shù)目顯著減少(P0.05);與模型對(duì)照組比較,低、高劑量干預(yù)組大鼠頸髓谷氨酸免疫反應(yīng)陽性細(xì)胞數(shù)目明顯降低(P0.05),GABA免疫陽性細(xì)胞數(shù)目明顯增多(P0.05),且呈劑量依賴性。結(jié)論:左乙拉西坦可以改善偏頭痛大鼠在行為學(xué)方面的變化,能使高頸髓谷氨酸能中間神經(jīng)元的數(shù)目降低,GABA能中間神經(jīng)元的數(shù)目增高,且呈劑量依賴性,其機(jī)制可能與調(diào)節(jié)高頸髓中間神經(jīng)元“興奮-抑制”穩(wěn)態(tài)的平衡有關(guān)。
[Abstract]:Aim: to observe the effect of levoxetam (Levo) on the behavior of migraine rats induced by nitroglycerin and the changes of glutaminergic and GABA interneurons in the cervical spinal cord of SD(Sprague Dawley rats. To explore the preventive and therapeutic effect of LEV on migraine and its possible mechanism. Method 1: 1. Twenty-four male Sprague-Dawley (SD) rats were fed for one week and were randomly divided into sham model group (n = 6) and model group (n = 18). The experimental migraine rat model was established by subcutaneous injection of nitroglycerin NTG, and the sham model group was given subcutaneous normal saline. The rats in the model group were randomly divided into control group (n = 6), low dose group (n = 6) and high dose group (n = 6). Sham model group: saline was administered once a day for 1 week, and then subcutaneously injected with normal saline after the last gastric perfusion. The model control group was treated with normal saline once a day for 1 week, then subcutaneously injected nitroglycerin after the last intragastric perfusion, and the model was made again. Low dose intervention group: levoethoxetam 100 mg/kg intragastric perfusion once a day for 1 week, after the last gastric perfusion, subcutaneous injection of nitroglycerin, re-model. High dose intervention group: levoethoxetam 200 mg/kg intragastric perfusion once a day for 1 week, after the last gastric perfusion, subcutaneous injection of nitroglycerin, re-model. 2. The behavioral changes of each rat were closely observed after successful modeling. As an observation time unit every half hour, the number of head scratching, cage crawling and head flick in each segment of 90min was observed by using the method of continuous time piecewise counting. After 3 hours of migraine model, intraperitoneal injection of anesthesia, formaldehyde perfusion, cervical spinal cord 1-2. Glutamate and 緯 -aminobutyric acid (GABA) were stained with immunohistochemical method. The number of glutamate and GABA immunoreactive cells was observed by optical microscope, and five high-power visual fields were observed randomly at the posterior horn of ipsilateral spinal cord. The number of positive cells was recorded in turn. The result is 1: 1. Behavioral changes: compared with the sham model group, the number of head scratching, the number of cage climbing and the number of head flick in the other groups were significantly increased (P 0.05). Compared with the model control group, the number of head scratching, the number of cage climbing and the number of head flick in the drug intervention group decreased with the increase of drug dosage. The number of Glutamic acid and GABA immunoreactive cells: compared with the pseudo-model group, the number of GA-immunoreactive cells in the other groups was significantly increased and the number of GABA-immunoreactive cells in the other groups was significantly decreased than that in the model control group, and was lower than that in the model control group. The number of glutamate immunoreactive cells in the cervical spinal cord decreased significantly in the high dose intervention group, and the number of GABA immunoreactive cells in the cervical spinal cord increased significantly in a dose-dependent manner. Conclusion: levoethylacetam can improve the behavioral changes of migraine rats and decrease the number of glutaminergic intermediate neurons in high cervical spinal cord in a dose-dependent manner. The mechanism may be related to regulating the balance of excitation-inhibition homeostasis of high cervical spinal cord interneuron.
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R747.2

【參考文獻(xiàn)】

相關(guān)期刊論文 前9條

1 嚴(yán)妤函;關(guān)欣穎;張成林;劉東;王成云;萬琪;;偏頭痛大鼠頸髓中間神經(jīng)元的變化及其對(duì)運(yùn)動(dòng)神經(jīng)元的影響[J];中國疼痛醫(yī)學(xué)雜志;2015年12期

2 倪紅;鄭卜真;王恩;金笑平;馬傳花;柯紹發(fā);周元林;儲(chǔ)照虎;;左乙拉西坦對(duì)急性癲癇小鼠海馬GABA能神經(jīng)元電生理的研究[J];中國臨床藥理學(xué)與治療學(xué);2015年05期

3 王維;陳興旺;陳春富;張君;郁飛宇;李繼川;;左乙拉西坦預(yù)防難治性偏頭痛的療效及安全性[J];中國神經(jīng)精神疾病雜志;2014年03期

4 楊慎峭;金榮疆;朱天民;馬紅彥;馮麗娟;毛雪蓮;;康復(fù)訓(xùn)練結(jié)合電針對(duì)腦卒中肢體痙攣大鼠γ-氨基丁酸能中間神經(jīng)元表達(dá)的影響[J];中國康復(fù)醫(yī)學(xué)雜志;2013年03期

5 黃露露;于世英;;神經(jīng)病理性疼痛的中樞敏化發(fā)病機(jī)制[J];中國疼痛醫(yī)學(xué)雜志;2011年08期

6 袁博博;羅國剛;;偏頭痛實(shí)驗(yàn)動(dòng)物模型的研究現(xiàn)狀[J];醫(yī)學(xué)綜述;2011年10期

7 王萍;田玉科;;神經(jīng)病理性疼痛脊髓機(jī)制的研究進(jìn)展[J];中國疼痛醫(yī)學(xué)雜志;2009年01期

8 GRILLNER Sten;;運(yùn)動(dòng)過程的網(wǎng)絡(luò)邏輯——從離子通道到動(dòng)物行為[J];生命科學(xué);2008年05期

9 周永紅,王新陸,胡懷強(qiáng),付先軍,劉偉;硝酸甘油型實(shí)驗(yàn)性偏頭痛大鼠模型建立與評(píng)價(jià)[J];中國神經(jīng)免疫學(xué)和神經(jīng)病學(xué)雜志;2005年02期

，

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