固醇调节元件结合蛋白活性增加在二噁英染毒大鼠肝脏脂质沉积中的作用及运动干预研究

目的：研究固醇调节元件结合蛋白（SREBP）在二噁英染毒大鼠肝脏中的表达及在脂质代谢紊乱中的作用，探讨运动干预能否改变二噁英染毒大鼠的脂质代谢，为通过运动防治二噁英引起的代谢性疾病提供相应的理论依据。方法：24只雄性SD大鼠进行随机分组，对照组、染毒组、运动染毒组，每组8只。染毒组、运动染毒组大鼠腹腔注射二噁英（2，3，7，8-TCDD），首次剂量为每公斤体重6.4微克，之后7周内，每隔1周按首次剂量的21%进行持续染毒。运动染毒组大鼠尾部以5%体重的负重量进行游泳运动，每天30分钟。8周后处死动物，计算肝脏指数，测定肝脏甘油三酯含量，肝脏组织HE和油红O染色检测病理性改变和脂肪沉积情况，Western Blot检测SREBP1-c蛋白表达含量，实时荧光定量PCR检测FASmRNA表达。结果：二噁英持续染毒大鼠肝脏中有明显脂质沉积现象。SREBP1-c活性及其靶基因FASmRNA表达显著增高，长期规律游泳运动能够显著降低这些蛋白和基因的表达。结论：二噁英染毒大鼠肝脏SREBP1-c活性显著增加，激活了脂质合成代谢FASmRNA的表达，从而促进脂质沉积。SREBP1-c可能是环境污染物二噁英导致代谢性疾病的重要转录因子。规律游泳运动可以逆转这种脂质沉积现象，提示游泳运动有助于降低二噁英染毒对大鼠的脂毒性作用，改善脂质代谢的紊乱。

Role of Increased Activity of SREBP in Excessive Lipid Accumulation in Liver of Dioxin Exposed Rat and Exercise Intervention Study

The objective was to study the expression and the role of the SREBP in excessive lipid deposition in the liver and to investigate whether exercise intervention could alter lipid metabolism in dioxin exposed rats at the aim of providing theoretical support for exercise might prevent metabolic diseases caused by dioxin. 24 SD rats were divided randomly into 3 groups:control group, toxic group, and exercise toxic group. Toxic and exercise toxic groups were intraperitoneally injected 2,3,7,8-TCDD. The first dose was 6.4 μg/kg·bw. A maintenance dosage by 21% of the first dose was administrated weekly for the following 7 weeks. Exercise toxic group swam 30 min every day with load of 5% body weight. At the 8th week, all of the rats were killed, the hepatic index was calculated, and biochemical indicators were detected. Histopathological changes and lipids deposition were evaluated by HE and oil red O staining. SREBP1-c protein expression was determined by Western Blot and FAS mRNA via real-time quantitative PCR. The results showed that significant lipid droplet deposition was detected, SREBP1-c protein and FAS mRNA expression increased significantly in the livers of dioxin exposed rats. Long-term exercise might significantly decrease FAS mRNA and protein expressions. The dioxin exposed rats exhibited significantly higher liver SREBP-1c activity, which might be associated with the development of hepatic lipid deposition. SREBP might be an important pathogenic factor of environmental pollutants dioxins leading to metabolic disease. Swimming exercise regularly could reverse the lipid deposition phenomenon. It showed that swimming exercise could help reduce Hepatic lipotoxicity in dioxin exposed rats, improve lipid metabolism disorders.