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。
Objective To observe the biometric characteristics of glueose and lipid metabolism of aP2-SREBP-lc transgenic mice, and to explore its application in the study of glucose and lipid metabolism disorder. Methods Female aP2-SREBP-Ic 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-lc mice were characterized by evident lipodystrophy, insulin resistance, hypercholesteremia and fatty liver when compared with the wild-type controlled group. Conclusion aP2-SREBP-lc 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.
出处
《中药新药与临床药理》
CAS
CSCD
北大核心
2014年第1期96-101,共6页
Traditional Chinese Drug Research and Clinical Pharmacology
基金
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)
