本文選題：納洛酮 + NG-硝基-L-精氨酸��； 參考：《山東農(nóng)業(yè)大學(xué)》2015年碩士論文

【摘要】：本試驗(yàn)用兔作為實(shí)驗(yàn)動物制備慢性酒精中毒模型,一氧化氮合酶抑制劑L-NNA及納絡(luò)酮對成功模型進(jìn)行比較治療。通過測定不同組慢性酒精中毒家兔額葉、海馬、紋狀體中NOS的活性、NO水平,觀測NOS陽性神經(jīng)元形態(tài)結(jié)構(gòu)及分布來探討慢性酒精中毒腦損傷與NO的關(guān)系以及L-NNA對受損腦組織中NOS活性、NO水平的影響,為慢性酒精中毒腦損傷機(jī)制、病理學(xué)研究以及臨床治療提供理論依據(jù)。通過酒精灌胃的方法建立家兔慢性酒精中毒模型,并通過體重、行為學(xué)變化以及病理組織學(xué)確定家兔是否已經(jīng)造成腦組織損傷。酒精灌胃的家兔在6周后體重出現(xiàn)負(fù)增長,經(jīng)病理組織學(xué)觀察可知:在酒精灌胃8周時,酒精灌胃家兔腦組織出現(xiàn)輕微的神經(jīng)元缺失,隨著灌胃時間的增長,腦組織神經(jīng)元缺失加重,且有細(xì)胞溶解消失,海馬區(qū)錐體細(xì)胞排列紊亂,免疫組織化學(xué)實(shí)驗(yàn)顯示nNOS及iNOS陽性神經(jīng)元在不同腦區(qū)的表達(dá)發(fā)生一定變化,進(jìn)一步驗(yàn)證了模型的可靠性。利用硝酸還原酶法和生物化學(xué)檢測方法來分別檢測各組家兔額葉、海馬、紋狀體內(nèi)的NOS活性變化及NO水平變化。結(jié)果顯示:模型組家兔額葉、海馬及紋狀體中NOS活性一直保持上升趨勢,且在各個時間點(diǎn)均顯著高于對照組,NO含量變化與其相一致;給予納洛酮及L-NNA后,治療組各腦區(qū)NOS及NO水平均上升緩慢,給藥3 d后均呈下降趨勢,14 d后變化趨于平穩(wěn),三組治療組不同腦區(qū)NOS活性及NO水平均顯著低于模型組。利用SABC免疫組織化學(xué)法在光學(xué)顯微鏡下對各組家兔額葉、海馬各區(qū)以及紋狀體的nNOS陽性神經(jīng)元與i NOS陽性神經(jīng)元的形態(tài)結(jié)構(gòu)進(jìn)行觀測。試驗(yàn)結(jié)果表明:各組兔腦組織內(nèi)nNOS和iNOS陽性神經(jīng)元的數(shù)量與NO的含量及NOS活性在腦組織中的變化趨勢基本一致。模型組、納洛酮組及L-NNA組中不同腦組織內(nèi)nNOS及iNOS陽性神經(jīng)元的表達(dá)顯著高于正常對照組,與酒精模型組相比,三組治療組腦內(nèi)NOS陽性神經(jīng)元的表達(dá)均有所降低,其中聯(lián)合治療組降低幅度最大。結(jié)果表明:酒精模型組中額葉、海馬及紋狀體中的神經(jīng)元缺失、死亡伴隨相應(yīng)組織中NO含量的增加以及nNOS和iNOS陽性神經(jīng)元表達(dá)增強(qiáng),而給予納洛酮及L-NNA治療后,治療組中NO水平、nNOS及iNOS陽性神經(jīng)元的表達(dá)均有所下降,家兔腦組織病理變化減輕,一般狀態(tài)及體重增長情況得到改善,提示慢性酒精中毒時腦組織的損傷可能是由NO參與介導(dǎo)的,而L-NNA及納絡(luò)酮均能抑制酒精中毒時NOS的活性,使額葉、海馬及紋狀體組織中NO水平降低,改善家兔的一般狀態(tài),為臨床上慢性酒精中毒的治療和新藥研發(fā)提供新的依據(jù)和方向。
[Abstract]:The model of chronic alcoholism was established in rabbits. The successful model was treated by nitric oxide synthase inhibitor (L-NNA) and naloxone. The activity of NOS in frontal lobe, hippocampus and striatum of rabbits with chronic alcoholism was measured. The morphological structure and distribution of NOS positive neurons were observed to explore the relationship between brain injury and no in chronic alcoholism and the effect of L-NNA on the level of NOS activity in the injured brain tissue, which was the mechanism of brain injury in chronic alcoholism. Pathological study and clinical treatment provide theoretical basis. The model of chronic alcoholism in rabbits was established by the method of alcohol administration, and the changes of body weight, behavior and histopathology were used to determine whether the rabbit had caused brain injury. The weight of rabbits fed with alcohol showed negative growth after 6 weeks. By histopathological observation, there was a slight neuronal deficiency in the brain tissue of the rabbits fed with alcohol for 8 weeks, and with the increase of the time of gastric perfusion, there was a slight loss of neurons in the brain tissue of the rabbits fed with alcohol for 8 weeks. The loss of neurons in brain tissue was aggravated, cell dissolution disappeared, and the pyramidal cells in hippocampus were disordered. Immunohistochemical experiments showed that the expression of nNOS and iNOS positive neurons in different brain regions changed to a certain extent. The reliability of the model is further verified. The changes of NOS activity and no level in frontal lobe, hippocampus and striatum of rabbits were detected by nitrate reductase method and biochemical method respectively. The results showed that the activity of NOS in frontal lobe, hippocampus and striatum of the model group maintained an increasing trend, and the content of no in the model group was significantly higher than that in the control group at each time point. The levels of NOS and no increased slowly in all brain regions of the treatment group, and showed a decreasing trend after 3 days of administration. The NOS activity and no level in different brain regions of the three treatment groups were significantly lower than those in the model group. The morphology of nNOS positive neurons and I NOS positive neurons in frontal lobe, hippocampus and striatum of rabbits were observed by SABC immunohistochemical method under optical microscope. The results showed that the number of nNOS and iNOS positive neurons in the brain tissue of each group was consistent with the content of no and the activity of NOS in the brain tissue. The expression of nNOS and iNOS positive neurons in different brain tissues in model group, naloxone group and L-NNA group were significantly higher than those in normal control group. Compared with alcohol model group, the expression of NOS positive neurons in brain of three treatment groups were decreased. In the combined treatment group, the decrease was the largest. The results showed that the loss of neurons in frontal lobe, hippocampus and striatum was accompanied by the increase of no content and the expression of nNOS and iNOS positive neurons in the corresponding tissues. After the treatment of naloxone and L-NNA, Naloxone and L-NNA were given. In the treatment group, the expression of nNOS and iNOS positive neurons were decreased, the pathological changes of brain tissue were alleviated, and the general state and weight gain were improved. L-NNA and naloxone could inhibit the activity of NOS, decrease the level of no in frontal lobe, hippocampus and striatum, and improve the general state of rabbits. To provide a new basis and direction for the clinical treatment of chronic alcoholism and the development of new drugs.
【學(xué)位授予單位】：山東農(nóng)業(yè)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：S858.291

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