氢盐水对非酒精性脂肪性肝炎的保护作用研究

发布时间：2018-04-24 10:35

本文选题：高脂高胆固醇饲料 + wistar大鼠　；参考：《川北医学院》2017年硕士论文

【摘要】：第一部分Wistar大鼠非酒精性脂肪性肝炎动物模型的建立目的:建立wistar大鼠非酒精性脂肪性肝炎(NASH)动物模型,为研究氢盐水对NASH的保护作用及其机制提供实验动物模型。方法:采用高脂高胆固醇模型饲料喂养wistar大鼠4-18周,从第4周开始,每周观察一次大鼠的肝脏是否发生脂肪变、炎细胞浸润及脂肪变和炎细胞浸润程度,最终确定恰当的喂养时间,成功构建NASH大鼠模型,为后续研究提供动物模型。结果:高脂饲料组在第4周时镜下可见脂肪沉积,但均为轻度的局部脂肪沉积,在第8周时镜下可见弥漫性的脂肪沉积,局部可见少量的炎性细胞浸润,第16周时镜下见肝脏中较多炎症细胞浸润,并可见点状坏死。高脂饲料组丙氨酸氨基转移酶(ALT)在第8周和第16周时和普通饲料组比较差异明显;天门冬氨酸氨基转移酶(AST)在第4周、第8周和第16周时和普通饲料组比较差异明显。高脂饲料组血总胆固醇(TC)和甘油三酯(TG)逐渐升高,且在第4周、第8周、第16周时和普通饲料组比较均有统计学差异。结论:使用高脂高胆固醇饲料喂养wistar大鼠,在第16周可形成稳定的非酒精性脂肪性肝炎动物模型。第二部分氢盐水对非酒精性脂肪性肝炎的保护作用研究目的:探讨氢盐水对NASH大鼠的治疗作用及具体作用机制。方法:将建模成功的wistar大鼠随机分为治疗组和对照组,治疗组自由饮用氢盐水,对照组自由饮用生理盐水。于治疗前、治疗后第1天、1周和4周分别检测两组大鼠的外周血生化指标(转氨酶、血脂、血糖等)、肝脏形态学改变、炎性细胞因子、信号转导通路等相关指标。结果:对照组和实验组大鼠胆固醇和甘油三酯均仍在持续增高,但是在同一观察时间对照组和实验组比较总胆固醇和甘油三酯没有差异。ALT和AST在治疗前和治疗后的第1天对照组和实验组比较没有差异,但是第1周和第4周比较差异明显。IL-6和TNFα的表达在治疗前和治疗后的第1天没有差异,但是第1周和第4周比较差异明显。Caspase-3的表达在治疗前、治疗后第1天和第1周时对照组和实验组比较没有差异,但是在第4周时对照组中的表达高于实验组,差异明显。结论:氢盐水作为一种选择性抗氧化剂,对NASH具有一定的保护作用。
[Abstract]:Part I the establishment of Wistar rat animal model of non-alcoholic fatty hepatitis objective: to establish an animal model of wistar rats with non-alcoholic fatty hepatitis, and to provide an experimental animal model for the study of the protective effect of hydrogen saline on NASH and its mechanism. Methods: wistar rats were fed with high fat and high cholesterol diet for 4-18 weeks. From the 4th week, the liver of rats was observed once a week to observe whether the liver had adiposis, inflammatory cell infiltration, fatty degeneration and inflammatory cell infiltration. Finally, the appropriate feeding time was determined, and the NASH rat model was successfully constructed, which provided the animal model for the follow-up study. Results: in the high fat diet group, fat deposits were observed under microscope at the 4th week, but they were mild local fat deposits, diffuse fat deposits were observed under the microscope at the 8th week, and a small amount of inflammatory cell infiltration was observed locally. At week 16, more inflammatory cells were infiltrated and punctate necrosis was observed in the liver. The alanine aminotransferase (alt) in high-fat diet group was significantly different from that in the general diet group at the 8th and 16th weeks, and the aspartate aminotransferase (AST) at the 4th, 8th and 16th weeks was significantly different from the normal diet group. The serum total cholesterol (TCC) and triglyceride (TG) increased gradually in the high fat diet group, and there were significant differences between the high fat diet group and the general diet group at the 4th week, the 8th week, the 16th week and the general diet group. Conclusion: wistar rats fed with high fat and high cholesterol diet can form a stable animal model of non-alcoholic fatty hepatitis at the 16th week. The second part of the study on the protective effect of hydrogen saline on non-alcoholic fatty hepatitis objective: to investigate the therapeutic effect of hydrogen saline on NASH rats and its specific mechanism. Methods: wistar rats were randomly divided into treatment group and control group. The peripheral blood biochemical indexes (transaminase, blood lipid, blood glucose, liver morphology, inflammatory cytokines, signal transduction pathway and so on) were measured before, 1 and 4 weeks after treatment. Results: the levels of cholesterol and triglyceride in the control group and experimental group were still increasing. But there was no difference in total cholesterol and triglyceride between the control group and the experimental group at the same observation time. There was no difference between the control group and the experimental group before treatment and on the first day after treatment. However, there was no significant difference in the expression of IL-6 and TNF 伪 between the first week and the fourth week, but the expression of Caspase-3 was significantly different before and after treatment. There was no difference between the control group and the experimental group on the first day and the first week after treatment, but the expression in the control group was higher than that in the experimental group at the 4th week, and the difference was significant. Conclusion: as a selective antioxidant, hydrogen salt has a protective effect on NASH.
【学位授予单位】：川北医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R575

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