本文選題：非酒精性脂肪性肝病 + 腸道微生態(tài)�。� 參考：《廣東藥學院》2014年碩士論文

【摘要】：目的 證明腸道微生態(tài)失衡是高脂飲食誘導的非酒精性脂肪性肝�。∟AFLD）發(fā)生發(fā)展的一個重要途徑，而合生元通過調(diào)節(jié)腸道菌群及影響TLR4的表達來改善NAFLD。 方法 采用高脂飲食喂養(yǎng)SD大鼠，構建NAFLD大鼠動物模型，分別于高脂飲食第4周末、第8周末、第12周末三個時間點給予各實驗組大鼠合生元口飼兩周后，取各組大鼠肝臟組織，進行HE染色，對其組織病理學改變進行評分，觀察各組大鼠肝臟組織學形態(tài)的改變，并測定肝臟組織中甘油三酯（TG）、膽固醇（TC）的含量，及血清空腹血糖（GLU）、空腹胰島素(FINS)、甘油三酯（TG）、膽固醇（TC）、天門冬氨酸氨基轉(zhuǎn)移酶（AST）、丙氨酸氨基轉(zhuǎn)移酶（ALT）、總膽固醇（TC）、總甘油三酯（TG）、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）等的含量，應用ELISA法和免疫組化方法測定大鼠腸道粘膜Toll樣受體4（TLR4）的表達水平，應用16s rRNA熒光定量PCR方法動態(tài)監(jiān)測大鼠腸道主要菌群的變化情況。 結(jié)果 1.高脂飲食組體重、肝指數(shù)、血清學指標TG、TC、AST、LDL、GLU、FINS水平顯著高于正常飲食組（P＜0.05），自主活動次數(shù)、飲食量、飲水量均顯著低于正常飲食組（P＜0.05）。經(jīng)過合生元干預2周可以使高脂飲食的大鼠血清學指標TG、TC、AST、LDL、GLU、FINS水平顯著降低，差異具有統(tǒng)計學意義（P＜0.05），ALT、HDL未見明顯差異，肝指數(shù)也有所下降，但差異不具有統(tǒng)計學意義（P＞0.05），自主活動次數(shù)、飲食量、飲水量顯著增高，差異具有統(tǒng)計學意義（P＜0.05）。 2.高脂飲食第4周，肝臟組織開始出現(xiàn)散在脂肪沉積；第8周，肝臟組織呈單純性脂肪變樣改變；第12周，肝臟組織出現(xiàn)了非酒精性脂肪性肝炎樣改變。分別在上述三個時間點給予合生元干預2周后，肝臟組織脂肪沉積情況改善不明顯，但并未發(fā)現(xiàn)脂肪沉積進一步惡化趨勢。 3.隨著實驗的進程，，高脂飲食組TLR4的表達量呈逐漸增高趨勢，且表達顯著高于正常飲食組，差異具有統(tǒng)計學意義（與正常飲食組相比P＜0.05），合生元干預2周后可顯著下調(diào)高脂飲食的大鼠TLR4的表達，差異具有統(tǒng)計學意義（與高脂飲食組相比P＜0.05）。 4.高脂飲食組大鼠從第2周開始，腸道菌群中雙歧桿菌和乳酸桿菌的表達量顯著下降，差異均具有統(tǒng)計學意義（與正常飲食組相比P＜0.05），腸球菌表達量出現(xiàn)顯著升高，差異具有統(tǒng)計學意義（與正常飲食組相比P＜0.05）。經(jīng)過合生元干預2周后，可使雙歧桿菌和乳酸桿菌的表達顯著上調(diào)，腸球菌的表達顯著下調(diào)，差異均具有統(tǒng)計學意義（與高脂飲食組相比P＜0.05）。 結(jié)論 高脂飲食誘導的大鼠NAFLD模型，先出現(xiàn)腸道菌群紊亂，而后出現(xiàn)肝臟病理學改變，應用合生元調(diào)節(jié)腸道菌群后，可以下調(diào)腸道粘膜TLR4的表達，調(diào)節(jié)血清學各項指標及改善生活質(zhì)量，從而達到治療NAFLD的效果，進一步證明了高脂飲食導致的腸道菌群紊亂是NAFLD發(fā)生發(fā)展的原因之一。
[Abstract]:Purpose The results suggest that intestinal microecological imbalance is an important pathway for the development of NAFLDs induced by high fat diet, while the synbiotic elements improve NAFLD by regulating intestinal flora and influencing the expression of TLR4. Method SD rats were fed with high-fat diet to establish NAFLD rat model. The liver tissues of each group were taken out at the 4th weekend, 8th weekend and 12th week of high fat diet. The histopathological changes were evaluated by HE staining, the histopathological changes of the liver were observed, and the contents of TGG and TCC in the liver were measured. And the contents of serum fasting blood glucose (GLU), fasting insulin (FINSN), triglyceride (TGN), cholesterol triglyceride (TC), aspartate aminotransferase (AST), alanine aminotransferase (alt), total cholesterol (TC), total triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), etc. The expression of Toll like receptor 4 (TLR4) in rat intestinal mucosa was determined by ELISA method and immunohistochemical method. The changes of main intestinal flora in rats were dynamically monitored by 16s rRNA fluorescence quantitative PCR method. Result 1. The levels of body weight, liver index, and serum TGN TCX LDLU fins in high fat diet group were significantly higher than those in normal diet group (P < 0.05), and the number of independent activities, diet quantity and drinking quantity were significantly lower than those in normal diet group (P < 0.05). After two weeks of intervention, the level of serum TGG TCX ASTX GLU fins in rats with high fat diet was significantly decreased, the difference was statistically significant (P < 0.05), and the liver index was also decreased, but the difference was not statistically significant (P > 0.05), and the number of independent activities was not significant. The quantity of diet and the quantity of drinking water were significantly increased, and the difference was statistically significant (P < 0.05). 2. In the 4th week of high-fat diet, the liver tissue began to appear scattered fat deposition; at the 8th week, the liver tissue showed simple fatty variant changes; at the 12th week, the liver tissue appeared non-alcoholic fatty hepatitis like changes. At the above three time points, the fat deposition in liver tissue did not improve significantly after two weeks of treatment with synbiotic elements, but no further deterioration of fat deposition was found. 3. With the development of the experiment, the expression of TLR4 in the high-fat diet group was gradually increased, and the expression was significantly higher than that in the normal diet group. The difference was statistically significant (P < 0.05) compared with the normal diet group. The expression of TLR4 in rats with high fat diet could be significantly down-regulated after 2 weeks of intervention by combining with Shengyuan (P < 0.05) compared with that of the high-fat diet group (P < 0.05). 4. The expression of Bifidobacterium and Lactobacillus in the intestinal flora of rats in the high-fat diet group decreased significantly from the second week (P < 0.05), and the expression of Enterococcus increased significantly compared with the normal diet group (P < 0.05). The difference was statistically significant (P < 0.05). After two weeks of intervention, the expression of Bifidobacterium and Lactobacillus could be upregulated significantly, and the expression of Enterococcus was significantly down-regulated (P < 0.05 compared with the high-fat diet group). Conclusion The NAFLD model of rats induced by high-fat diet showed intestinal microflora disorder first, and then liver pathological changes. The expression of TLR4 in intestinal mucosa could be down-regulated by using synbiotic elements to regulate intestinal microflora. To regulate the serological indexes and improve the quality of life, so as to achieve the effect of treatment of NAFLD, which further proves that the intestinal flora disorder caused by high-fat diet is one of the reasons for the occurrence and development of NAFLD.
【學位授予單位】：廣東藥學院
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R575.5

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