本文選題：偏頭痛 + 左乙拉西坦　； 參考：《山西醫(yī)科大學》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,造實驗性偏頭痛大鼠模型,假模型組大鼠給予皮下生理鹽水。造模成功后采用隨機方法將模型組中大鼠分為模型對照組(6只)、低劑量干預組(6只)及高劑量干預組(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,進行皮下注入生理鹽水。模型對照組:生理鹽水灌胃,1次/日,連續(xù)1周,待末次灌胃后,進行皮下注入硝酸甘油,再次造模。低劑量干預組:左乙拉西坦100 mg/kg灌胃,1次/日,連續(xù)1周,待末次灌胃后,進行皮下注入硝酸甘油,再次造模。高劑量干預組: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方面的改變。每半個小時作為一個觀察時間單元,采取持續(xù)時間分段計數(shù)的方式觀察90min內各個分段時間的大鼠撓頭、爬籠和甩頭的次數(shù)。3.復制偏頭痛模型3h后,給予腹腔注射麻醉,進行甲醛灌注,取頸髓1-2。用免疫組化方法對谷氨酸(Glu)和γ-氨基丁酸(GABA)染色,然后用光學顯微鏡觀察谷氨酸和GABA免疫陽性細胞的數(shù)目,并在同側脊髓后角部位隨機觀察5個高倍視野,依次記錄陽性細胞數(shù)目。結果:1.行為學變化:與假模型組對照,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)。與模型對照組比較,藥物干預組大鼠撓頭次數(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免疫陽性細胞數(shù)目:與假模型組比較,其余各組的谷氨酸免疫陽性細胞數(shù)目顯著增多(P0.05),GABA免疫陽性細胞數(shù)目顯著減少(P0.05);與模型對照組比較,低、高劑量干預組大鼠頸髓谷氨酸免疫反應陽性細胞數(shù)目明顯降低(P0.05),GABA免疫陽性細胞數(shù)目明顯增多(P0.05),且呈劑量依賴性。結論:左乙拉西坦可以改善偏頭痛大鼠在行為學方面的變化,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,其機制可能與調節(jié)高頸髓中間神經(jīng)元“興奮-抑制”穩(wěn)態(tài)的平衡有關。
[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.
【學位授予單位】：山西醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R747.2

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