亚硒酸钠通过逆转甲状腺激素转化异常改善非酒精性脂肪肝病变

发布时间：2018-07-29 06:15

【摘要】：目的探讨在NAFLD发生、发展过程中甲状腺激素的转化情况，了解甲状腺激素水平与脂代谢紊乱的关系。研究应用亚硒酸钠干预甲状腺激素转化异常能否防治NAFLD。方法（1）健康雄性SD大鼠64只，随机分为模型组和正常组，每组32只。模型组采用高脂饲料喂养建立非酒精性脂肪肝模型，正常组则采用常规饲料喂养。分别于0、4、8、12周时观察各组大鼠体重、肝湿重、肝指数，检测上述各时间点各组大鼠血清AST、ALT、TC、TG、HDL-C、LDL-C、T3、T4、rT3和肝脏硒含量与5′-脱碘酶活性。同时取各组各时间点病理切片行HE和Masson染色，观察大鼠肝组织病理学改变。（2）健康雄性SD大鼠96只，随机分为正常组、模型组和亚硒酸钠组，每组32只，正常组和模型组喂养方法如上述，亚硒酸钠组在高脂饮食喂养4周后再辅以亚硒酸钠（0.2mg/kg）灌胃。各组大鼠一般指标、血清学指标及病理学检测如上所述。结果 1、（1）一般指标：模型组大鼠12周时体重、肝湿重及肝指数显著高于对照组（P＜0.05）。（2）病理学检测：模型组大鼠12周时肝组织可见明显脂肪变，炎性细胞浸润，汇管区纤维化。（3）血清学指标：模型组大鼠12周时血清AST、ALT、TC、TG、LDL-C水平均有显著的升高，与之前各时间点相比，差异均具有统计学意义（P＜0.05）。（4）甲状腺激素水平：模型组血清T3和T4水平逐渐下降，rT3水平升高，在8周和12周时，与正常组相比，差异均具有统计学意义（P＜0.05）。（5）肝脏5′-脱碘酶活性及硒含量：模型组大鼠5′-脱碘酶活性和硒含量水平逐渐下降，与正常组相比，，差异均具有统计学意义（P＜0.05）。 2、（1）一般指标：亚硒酸钠组大鼠12周时体重、肝湿重及肝指数均小于模型组（P＜0.05）。（2）病理学检测：亚硒酸钠组大鼠12周时肝组织脂肪沉积及纤维化程度显著低于模型组。（3）血清学指标：亚硒酸钠组大鼠的血清AST、ALT、TC、TG、LDL-C水平4周后低于同时间点的模型组，差异具有统计学意义（P＜0.05）。（4）甲状腺激素水平：亚硒酸钠组大鼠血清T3、T4水平有所下降，rT3水平稍有升高，12周时与正常组接近，与模型组相比，差异具有统计学意义（P＜0.05）。（5）肝脏5′-脱碘酶活性及硒含量：亚硒酸钠组大鼠肝脏5′-脱碘酶活性和硒含量在4周后逐渐升高，12周时水平与正常组接近，与模型组相比，差异具有统计学意义（P＜0.05）。结论 1.通过高脂诱导的NAFLD模型大鼠血清T3、T4水平显著下降，rT3水平则显著上升，提示甲状腺激素水平异常与NAFLD的发病密切相关。 2. NAFLD大鼠肝脏5′-脱碘酶活性及硒含量显著下降，与甲状腺激素转化异常相关。 3.亚硒酸钠可使NAFLD大鼠肝组织硒含量及5′-脱碘酶活性升高，甲状腺激素转化异常状态得到改善，血清血脂紊乱和肝脏脂质沉积及纤维化程度减轻。
[Abstract]:Objective to investigate the relationship between thyroid hormone level and lipid metabolism disorder during the development of NAFLD. To study the effect of sodium selenite on thyroid hormone transformation. Methods (1) 64 healthy male SD rats were randomly divided into model group and normal group with 32 rats in each group. The model group was fed with high fat diet to establish the model of non alcoholic fatty liver, while the normal group was fed with conventional diet. The body weight, liver wet weight and liver index were observed at the 12th week of each group, and the serum levels of ASTT TCU, HDL-C, LDL-C, LDL-C, T4 rT3 and the activity of 5-tida-deiodinase in the liver were measured at 12 weeks. At the same time, the pathological sections of each group were stained with HE and Masson. (2) 96 healthy male Sprague-Dawley rats were randomly divided into normal group, model group and sodium selenite group with 32 rats in each group. Sodium selenite group was fed with sodium selenite (0.2mg/kg) for 4 weeks after high fat diet. The general index, serological index and pathological examination of rats in each group were as mentioned above. Results 1, (1) General measures: the body weight, liver wet weight and liver index in the model group were significantly higher than those in the control group at 12 weeks (P < 0. 05). (2). (3) serological indicators: the serum levels of LDL-C in serum of rats in the model group were significantly increased at 12 weeks, compared with the previous time points. The serum T3 and T4 levels of the model group decreased gradually and the RT3 level increased gradually, and at the 8th and 12th week, compared with the normal group, the serum T3 and T4 levels in the model group were significantly higher than those in the normal group, and the difference was statistically significant (P < 0. 05). (4). The difference was statistically significant (P < 0. 05). (5). The activity and selenium content of 5- deiodinase and selenium in the liver of the model group decreased gradually, compared with the normal group. The difference was statistically significant (P < 0.05). 2, (1) General measures: the body weight of sodium selenite group was 12 weeks, Liver wet weight and liver index were lower than model group (P < 0. 05). (2) pathological examination: the degree of hepatic fat deposition and liver fibrosis in sodium selenite group was significantly lower than that in model group at 12 weeks. (3) serological index: serum ASTTA TCU TGG LDL-C in sodium selenite group was significantly lower than that in model group (P < 0. 05). (2). After 4 weeks, the level was lower than that of the model group at the same time point. The difference was statistically significant (P < 0. 05). (4). The serum T3T4 level of sodium selenite group decreased slightly and the RT3 level increased slightly after 12 weeks, which was similar to that of the normal group, and compared with the model group. The difference was statistically significant (P < 0. 05). (5). The activity and selenium content of liver 5- deiodinase and selenium in sodium selenite group were increased gradually after 4 weeks and were close to those in the normal group at 12 weeks, compared with the model group, and the content of selenium in the liver of the sodium selenite group was similar to that of the control group. The difference was statistically significant (P < 0.05). Conclusion 1. The serum T3T4 level in NAFLD model rats induced by hyperlipidemia was significantly decreased and RT3 level was significantly increased, suggesting that the abnormal thyroid hormone level was closely related to the pathogenesis of NAFLD. 2. The activity of 5- deiodinase and the content of selenium in the liver of NAFLD rats were significantly decreased, which was related to the abnormal transformation of thyroid hormone. Sodium selenite could increase the content of selenium in liver tissue and the activity of 5- deiodinase in NAFLD rats, improve the abnormal state of thyroid hormone transformation, reduce the disorder of serum lipids and liver lipid deposition and reduce the degree of hepatic fibrosis.
【学位授予单位】：南华大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R575.5

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