n-3多不饱和脂肪酸对2型糖尿病大鼠肝脏脂质沉积的影响  

Influence of n-3 Polyunsaturated Fatty Acids on Liver Lipidomics in Type 2 Diabetic Rats

作　　者：鲁敏[1] 文秀英[2] 许明旺[2] 黄文凡[1] 刘丽芳[1] 许诣[1] 

机构地区：[1]华中科技大学同济医学院附属梨园医院内分泌科,武汉430077 [2]华中科技大学同济医学院附属梨园医院中西医结合科,武汉430077

出　　处：《中国药学杂志》2010年第7期510-515,共6页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助项目(30672730)

摘　　要：目的观察n-3多不饱和脂肪酸(n-3-PUFAs)对2型糖尿病大鼠糖脂代谢和肝脏脂质沉积的影响,并探讨其可能的分子机制。方法用高脂高糖饲料喂养加链脲佐菌素(STZ)腹腔注射方法建立的2型糖尿病模型。将成模大鼠随机分为模型组8只、n-3-PUFAs组和格列喹酮组各10只,另设正常对照组10只,持续灌胃12周。比较用药前、用药6周和12周末各组大鼠体重、血清空腹血糖(FBG)、甘油三酯(TG)、总胆固醇(TC)水平。断头处死大鼠后,比较各组大鼠腹腔内脂肪指数、肝脏指数、肝脏脂肪变程度和肝组织TG、TC含量;并用RT-PCR法检测肝组织固醇调节元件结合蛋白-1c(SREBP-1c)、脂肪酸合成酶(FAS)和乙酰辅酶A羧化酶(ACC)mRNA的表达;Western印迹法检测肝组织SREBP-1蛋白的表达。结果n-3-PUFAs组大鼠腹腔脂肪指数和体重均较模型组明显增加(P<0.01),血清TG降低(P<0.01),肝脏TG含量、肝指数及肝脏脂肪变程度记分升高(P<0.01),肝组织SREBP-1c、FAS和ACCmRNA表达升高(P<0.01),肝组织SREBP-1蛋白表达升高(P<0.01)。结论n-3-PUFAs能降低血清TG,但会导致腹腔脂肪增加及肝脏脂质沉积,与n-3-PUFAs不能抑制2型糖尿病状态下SREBP-1c及其下游脂肪合成相关酶FAS及ACC的表达有关。OBJECTIVE To study the influence of n-3 polyunsaturated fatty acids （n-3-PUFAs） on liver lipidomies in type 2 diabetic rats, and to investigate the possible molecular mechanism. METHODS Type 2 diabetes rats were induced by high-fat and high-sugar diet followed with streptozotocin injection. All rats were randomly divided into four groups ： the control group, the model group, the n-3-PUFAs group and gliquidone（Glurenor） group. The animals were sacrificed after the 12 weeks of administration. The fasting blood glucose, the weight of liver, the index of liver, TG and TC contents in liver and serum were measured. The level of SREBP-1 in liver was measured by Western blot. SREBP-1 mRNA, FAS mRNA and ACC mRNA expressions were measured with RTPCR. RESULTS The rats in n-3-PUFAs group showed characters of obesity. The TG in serum of the n-3-PUFAs group was lower than that in the model group （ P 〈0. 01 ）. The TG contents in liver, the weight of liver and the index of liver were higher than those of model group（ P 〈 0. 01 ）. The expression levels of SREBP-1c, FAS and ACC mRNA in the n-3-PUFAs group were higher than those in the model group（P 〈 O. 01 ）. CONCLUSION Although n-3-PUFAs reduces the level of serum TG, it causes obesity and liver lipido- mics, and it can＇t suppress the overexpression of SREBP-1c, FAS and ACC in the liver of type 2 diabetic rats.

关 键 词：N-3多不饱和脂肪酸 2型糖尿病 脂质沉积 固醇调节元件结合蛋白-1C 

分 类 号：R965[医药卫生—药理学]