本文選題：高脂高膽固醇飼料 + wistar大鼠�。� 參考：《川北醫(yī)學院》2017年碩士論文

【摘要】：第一部分Wistar大鼠非酒精性脂肪性肝炎動物模型的建立目的:建立wistar大鼠非酒精性脂肪性肝炎(NASH)動物模型,為研究氫鹽水對NASH的保護作用及其機制提供實驗動物模型。方法:采用高脂高膽固醇模型飼料喂養(yǎng)wistar大鼠4-18周,從第4周開始,每周觀察一次大鼠的肝臟是否發(fā)生脂肪變、炎細胞浸潤及脂肪變和炎細胞浸潤程度,最終確定恰當?shù)奈桂B(yǎng)時間,成功構(gòu)建NASH大鼠模型,為后續(xù)研究提供動物模型。結(jié)果:高脂飼料組在第4周時鏡下可見脂肪沉積,但均為輕度的局部脂肪沉積,在第8周時鏡下可見彌漫性的脂肪沉積,局部可見少量的炎性細胞浸潤,第16周時鏡下見肝臟中較多炎癥細胞浸潤,并可見點狀壞死。高脂飼料組丙氨酸氨基轉(zhuǎn)移酶(ALT)在第8周和第16周時和普通飼料組比較差異明顯;天門冬氨酸氨基轉(zhuǎn)移酶(AST)在第4周、第8周和第16周時和普通飼料組比較差異明顯。高脂飼料組血總膽固醇(TC)和甘油三酯(TG)逐漸升高,且在第4周、第8周、第16周時和普通飼料組比較均有統(tǒng)計學差異。結(jié)論:使用高脂高膽固醇飼料喂養(yǎng)wistar大鼠,在第16周可形成穩(wěn)定的非酒精性脂肪性肝炎動物模型。第二部分氫鹽水對非酒精性脂肪性肝炎的保護作用研究目的:探討氫鹽水對NASH大鼠的治療作用及具體作用機制。方法:將建模成功的wistar大鼠隨機分為治療組和對照組,治療組自由飲用氫鹽水,對照組自由飲用生理鹽水。于治療前、治療后第1天、1周和4周分別檢測兩組大鼠的外周血生化指標(轉(zhuǎn)氨酶、血脂、血糖等)、肝臟形態(tài)學改變、炎性細胞因子、信號轉(zhuǎn)導通路等相關(guān)指標。結(jié)果:對照組和實驗組大鼠膽固醇和甘油三酯均仍在持續(xù)增高,但是在同一觀察時間對照組和實驗組比較總膽固醇和甘油三酯沒有差異。ALT和AST在治療前和治療后的第1天對照組和實驗組比較沒有差異,但是第1周和第4周比較差異明顯。IL-6和TNFα的表達在治療前和治療后的第1天沒有差異,但是第1周和第4周比較差異明顯。Caspase-3的表達在治療前、治療后第1天和第1周時對照組和實驗組比較沒有差異,但是在第4周時對照組中的表達高于實驗組,差異明顯。結(jié)論:氫鹽水作為一種選擇性抗氧化劑,對NASH具有一定的保護作用。
[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 偽 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.
【學位授予單位】：川北醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R575

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