[关键词]
[摘要]
目的 观察aP2-SREBP-1c转基因小鼠糖脂代谢生物特征,探讨其在糖脂代谢紊乱性疾病研究中的应用。方法 动物分为aP2-SREBP-1c转基因小鼠及其同窝野生型小鼠2组,均为雌性,观察两组小鼠体质量、进食量、进水量,不禁食及禁食12 h血中TG、TC、LDL-C、Glu水平,肝脏、肌肉脂质含量,口服糖耐量、胰岛素及瘦素,稳态胰岛素(HOMA-IR),脂肪、肝脏病理组织学变化。结果 与野生型比较,aP2-SREBP-1c转基因小鼠肾周、性腺周围、皮下脂肪均明显减少(P<0.01),褐色脂肪明显增加(P<0.01),肝脏切片显示明显脂肪肝病理变化,肝脏质量明显增加(P<0.01),血中胰岛素、葡萄糖水平及HOMA-IR明显增加(P分别<0.01、0.05、0.001),瘦素明显下降(P<0.01),禁食状态血中TC、LDL-C水平均显著升高(P < 0.05,P <0.01),显示存在明显的脂肪分化障碍、胰岛素抵抗、高胆固醇血症和脂肪肝。结论 aP2-SREBP-1c转基因小鼠可用于糖尿病、脂肪肝、高胆固醇血症等糖脂代谢紊乱疾病的研究。
[Key word]
[Abstract]
Objective To observe the biometric characteristics of glucose and lipid metabolism of aP2-SREBP-1c transgenic mice,and to explore its application in the study of glucose and lipid metabolism disorder. Methods Female aP2-SREBP-1c transgenic mice and their wild type littermates were investigated. General data of body weight,food-intake and drink-intake were monitored. Metabolic parameters such as fed and fasting plasma glucose,TG,TC,LDL-C,hepatic TC,TG and muscular TG, fasting blood glucose(FBG),insulin,leptin, HOMA-IR were tested. Histological changes in fat tissue and hepatic tissue were observed after hematoxylin and eosin staining. Results Compared to their wild type littermates,weight of perirenal fat,peri-gonad fat,subcutaneous fat lose in the transgenic mice(P < 0.01),while weight of brown adipose tissue and liver gained(P < 0.01). Liver biopsy showed significantly pathological changes of fatty liver. Plasma insulin,glucose and HOMA-IR raised significantly(P < 0.01,P < 0.05,P < 0.001),while plasma leptin level decreased(P < 0.01). Lipid metabolic indicators such as fasting plasma TC and LDL-C were higher(P < 0.05,P < 0.01). The results indicated that aP2-SREBP-1c mice were characterized by evident lipodystrophy,insulin resistance,hypercholesteremia and fatty liver when compared with the wild-type controlled group. Conclusion aP2-SREBP-1c transgenic mice can be used as the advisable mouse model for the study of glucose and lipid metabolism disorder such as insulin resistance,fatty liver and hypercholesteremia.
[中图分类号]
R285.5
[基金项目]
教育部“新世纪优秀人才计划”(NCET-11-0916);国家自然科学基金面上项目(81274156);广州市科技攻关专项(2012J4100095)。