【摘要】：目的： 通過觀察厄多司坦對癲癇模型大鼠海馬中超氧化物岐化酶(SOD)活力、丙二醛(MDA)含量的變化和神經(jīng)元的病理損害程度及腦源性神經(jīng)營養(yǎng)因子水平變化,探討其抗癲癇病作用的可能機理。 方法: 選取健康雄性SD大鼠40只,分為正常對照組、戊四氮組、厄多司坦干預(yù)組和丙戊酸鈉組,每組各10只。腹腔注戊射四氮誘導(dǎo)癲癇發(fā)作,厄多司坦干預(yù)組和丙戊酸鈉組在點烯癲癇之前,各使用厄多司坦(50mg/Kg)和丙戊酸鈉(100mg/Kg)灌胃進行預(yù)處理。右側(cè)海馬測定SOD活力及MDA含量,左側(cè)海馬經(jīng)免疫組化染色方法觀察BDNF陽性細胞分布情況,HE染色觀察大鼠海馬神經(jīng)元損傷情況。 結(jié)果： 1.大鼠海馬SOD活力及MDA水平：癲癇發(fā)作后戊四氮組與對照組比較,SOD活力顯著降低(p0.01),厄多司坦干預(yù)組較戊四氮組升高(p0.01),厄多司坦干預(yù)組與丙戊酸鈉組比較,無明顯差異(p0.05)；致四氮組與對照組比較MDA含量顯著長高(p0.01),厄多司坦干預(yù)組較戊四氮組降低(p0.01),厄多司坦干預(yù)組與丙戊酸鈉組比較無明顯差異(p0.05)。 2.HE染色結(jié)果：對照組大鼠海馬神經(jīng)元排列緊密,邊緣清晰,胞漿透明,細胞核形態(tài)正常,無壞死性神經(jīng)元。戊四氮組大鼠海馬神經(jīng)元排列散亂,數(shù)目減少,胞體皺縮及核固縮,出現(xiàn)大量壞死性神經(jīng)元,厄多司坦干預(yù)組和丙戊酸鈉組可見散在壞死性神經(jīng)元。戊四氮組與對照組比較,有顯著差異(p0.01)；厄多司坦干預(yù)組與戊四氮組比較,有差異(p0.05)；厄多司坦干預(yù)組與丙戊酸鈉組比較,無明顯差異(p0.05)。 3.BDNF陽性表達：戊四氮組與對照組比較,染色強度顯著增強(p0.01),與厄多司坦干預(yù)組比較,染色強度較降低(p0.05)；厄多司坦干預(yù)組與丙戊酸鈉組比較,無明顯差異(p0.05)。 結(jié)論: 厄多司坦能減輕癲癇大鼠海馬氧化應(yīng)激水平,預(yù)處理不能完全防止癲癇發(fā)生,但可以減輕神經(jīng)元損傷程度,提示其神經(jīng)保護作用的存在。厄多司坦可能通過清除戊四氮點燃大鼠海馬中多余的自由基及增加海馬BDNF的表達而而參與神經(jīng)元保護機制。
[Abstract]:Objective: to observe the changes of superoxide dismutase (SOD) activity, malondialdehyde (MDA) (MDA) content in hippocampus of epileptic model rats, the degree of neuronal pathological damage and the level of brain-derived neurotrophic factor (BDNF). To explore the possible mechanism of its antiepileptic effect. Methods: forty healthy male SD rats were divided into normal control group, pentylenetetrazol group, erdostam intervention group and sodium valproate group with 10 rats in each group. The epileptic seizures were induced by intraperitoneal injection of pentylenetetrazole, and pretreated by oral administration of 50mg/Kg and 100mg/Kg, respectively, in the Edostam intervention group and sodium valproate group. The activity of SOD and the content of MDA were measured in the right hippocampus, the distribution of BDNF positive cells in the left hippocampus was observed by immunohistochemistry, and the damage of hippocampal neurons was observed by HE staining. Results: 1. SOD activity and MDA level in hippocampus of rats: compared with control group, SOD activity in pentylenetetrazol group was significantly lower than that in control group (p0.01), and that in erdostam intervention group was higher than that in pentylenetetrazol group (p0.01), and that in erdostam intervention group was higher than that in pentylenetetrazol group (p0.01). There was no significant difference (p0.05). Compared with the control group, the content of MDA in the tetrazole group was significantly higher than that in the control group (p0.01), the content of MDA in the erdostane group was lower than that in the pentylenetetrazol group (p0.01), but there was no significant difference between the two groups (p0.05). The results of 2.HE staining showed that the hippocampal neurons in the control group were closely arranged, with clear edges, clear cytoplasm, normal nuclear morphology and no necrotic neurons. In pentylenetetrazol group, the number of hippocampal neurons was scattered, the number of neurons was decreased, and a large number of necrotic neurons appeared in the shrinkage of the cell body and nucleus, and the necrotic neurons were found in the erdostam intervention group and sodium valproate group. There was significant difference between pentylenetetrazol group and control group (p0.01), and there was no significant difference between the two groups (p0.05). The positive expression of 3.BDNF: the staining intensity of pentylenetetrazol group was significantly higher than that of control group (p0.01), and the staining intensity of pentylenetetrazol group was lower than that of erdostam intervention group (p0.05). There was no significant difference between the treatment group and sodium valproate group (p 0.05). Conclusion: Erdostam can reduce the level of oxidative stress in hippocampus of epileptic rats. Preconditioning can not completely prevent the occurrence of epilepsy, but can reduce the degree of neuronal injury, suggesting the existence of neuroprotective effect. Erdostantan may be involved in neuronal protection by scavenging excess free radicals and increasing the expression of BDNF in hippocampus of pentylenetetrazol kindled rats.
【學(xué)位授予單位】：延邊大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R742.1

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