【作者】 吴高峰；

【导师】 胡建民；

【作者基本信息】 沈阳农业大学 ， 基础兽医学， 2006， 硕士

【摘要】 肝脏是酒精代谢的主要器官，大量饮酒会造成严重的肝脏损伤。目前酒精性肝病(ALD)在西方国家是肝脏相关疾病发病率和死亡率的主要病因。在我国，随着人民生活水平的不断提高，嗜酒者逐渐增多，ALD发病率也迅速上升。 研究证明牛磺酸具有广泛的生物学作用，能够维持血液、免疫、生殖系统、视觉、心血管系统、神经系统的正常结构和功能。近年来，有报道证明了牛磺酸能减轻四氯化碳所致的大鼠肝脏损伤，但对于其抗酒精性肝病的报道尚少，且均处于初始阶段。因此，本研究依据牛磺酸作用范围广、特异性低的特点，开展牛磺酸对大鼠酒精性肝病预防和治疗作用及其机理的探讨，旨在通过向人类饮食中添加牛磺酸，制备功能性食品，从而有效的预防酒精性肝病的发生，并为酒精性肝病的治疗提供新的途径。 本实验通过给雄性Wistar大鼠灌胃白酒和吡唑的混合液，饲喂高脂饲料的方法制备大鼠酒精性肝损伤模型，分别进行预防和治疗实验。预防实验分为五组：对照组和模型组大鼠正常饮水；β丙氨酸组大鼠造模的同时在饮水中添加1％β丙氨酸，造成大鼠内源性牛磺酸耗竭；预防组大鼠造模的同时在饮水中分别添加1％和2％的牛磺酸，时间12周。治疗实验分为四组：正常对照组和自然恢复组大鼠正常饮水；牛磺酸治疗组分别在ALD大鼠饮水中添加1％和2％牛磺酸，时间为4周。实验结束后杀鼠取血及肝脏，检测大鼠血清及肝脏中相关生理生化指标，并制作大鼠肝脏石蜡切片，HE染色分析病理变化。 实验结果表明：牛磺酸可以明显改善酒精对大鼠造成的机体损伤，能提高大鼠体增重，抑制大鼠肝脏指数的升高；维持肝脏功能，降低ALD大鼠血清中AST、ALT水平，升高肝组织总蛋白含量；提高大鼠肝组织中SOD、GSH活性，降低MDA含量，从而抑制酒精刺激所造成的肝脏脂质过氧化的发生；而且牛磺酸还能显著降低大鼠血清IL-2、IL-6、TNF-α的水平，抑制细胞因子的异常升高，保护肝脏不受酒精引起的免疫损伤；牛磺酸可以通过抑制大鼠肝脏中iNOS表达，降低肝脏中NO的含量，从而使eNOS催化生成的NO维持在正常范围内，起到保护肝脏的作用，进而改善酒精引起的肝损伤；此外，牛磺酸还能够抑制并逆转酒精性肝损伤导致的肝脏Hyp含量和血清HA、LN水平的升高，说明牛磺酸能够预防并治疗酒精性肝病大鼠的纤维化病变；观察大鼠肝组织病理切片并进行定量分析发现，牛磺酸能明显减轻由乙醇造成的肝细胞脂肪变性以及坏死程度，减少炎性细胞浸润及纤维沉积，且所有结果均显示2％牛磺酸对大鼠ALD具有较为显著的预防和治疗效果。更多还原

【Abstract】 The liver is considered to be the main organ capable of oxidizing alcohol, and drinking too much will damage the liver acutely. ALD has aroused great interests all over the world. In china, with the development of livingstandard, the rate of ALD has increased day by day.There are significant evidence suggesting that taurine has various biologic effects such as maintaining the normal structures and functions of hematological system, immune system, genital system, visual system, cardiovascular system and nervous system. Recently, people have paid close attention to the effects of taurine on alimentary system.Taurine has been reported to relieve the liver damage caused by CCl₄, however there are few information about the effects of taurine on ALD.The current study was to show whether taurine have both preventive and curative effects on ALD, and try to discuss the mechanisms of the protective effects of taurin of ALD.Alcohol was administrated to male Wistar rats by way of intragastric administration. Meanwhile, high fat diets were fed to the rats in order to establish the models of ALD rats. The whole research includes preventive and curative experiments.The rats were divided into four groups: the rats in the control and the model groups drank normal water, while the rats in β-Ala and taurine preventive groups drank water containing 1% β-Ala, 1% and 2% taurine respectively. The preventive experiment lasted for 12 weeks. In the curative experiment, the rats were divided into four groups either. The rats in the control and spontaneous recovery groups drank normal water, while the taurine curative effects drank water containing 1 % and 2% taurine respectively.The results showed that taurine can significantly reverse the damage caused by alcohol, increase the body weight and inhibit the increase of liver index.Also, taurine can decrease the levels of AST and ALT in the blood serum, increase the total protein of the liver.Another mechanism may be that taurine can increase the activities of SOD and GSH in the liver, and decrease the content of MDA, thus taurine can inhibit the peroxidation induced by alcohol.What s more, taurine can decrease the levels of IL-2、 IL-6 and TNF-a in the blood serum,更多还原