生物学杂志

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Adipsin腺病毒载体构建及对2型糖尿病大鼠的治疗作用

  

  1. 中国医学科学院 北京协和医学院 医学生物学研究所 云南省重大传染病疫苗研发重点实验室, 昆明 650118
  • 出版日期:2016-10-18 发布日期:2016-10-18
  • 通讯作者: 李鸿钧,研究员,长期从事干细胞及分子生物学相关研究,E-mail:lihj6912@hotmail.com
  • 作者简介:张磊,硕士,研究方向为生物化学与分子生物学,E-mail:635565654@qq.com
  • 基金资助:
    云南省科技计划项目(2014BC008);协和青年基金资助和中央高校基本科研业务费专项资金资助(33320140082)

Construction of adenovirus vector containing adipsin and  its therapy on 2 type diabetes rat model

  1. Yunnan Key Laboratory for Infectious Disease Major Vaccine Development, Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming 650118, China
  • Online:2016-10-18 Published:2016-10-18

摘要:

脂肪因子adipsin是由脂肪细胞分泌的一类细胞信号蛋白,其在刺激胰岛素分泌、控制血糖中具有重要的调控作用。以重组腺病毒系统作为载体,将adipsin转移至Zucker Diabetic Fatty (ZDF) 2型糖尿病大鼠体内,对大鼠进行基因治疗探索,为进一步研究脂肪因子adipsin与代谢性疾病如2型糖尿病等之间相互作用机制提供了前期的基础。首先,通过构建携带adipsin的重组腺病毒质粒pAdEasy-CMV-adipsin,并在HEK293细胞中成功包装出重组腺病毒Ad-adipsin;其次,通过PCR和Western blotting检测ADIPSIN蛋白在HEK293细胞中的表达;最后,测定重组腺病毒Ad-adipsin滴度,并通过尾静脉注射的方式,将重组腺病毒Ad-adipsin导入2型糖尿病模型大鼠体内,评价脂肪因子adipsin的基因治疗作用。研究结果显示, 2型糖尿病模型大鼠ZDF(fa/fa)的空腹血糖值(FPG)、空腹胰岛素值(FINS)、血清总胆固醇(TC)、甘油三脂(TG)、低密度脂蛋白(LDL-c)等与注射重组腺病毒Ad-lacZ的对照组相比有显著下降(P<0.05),并且胰岛素抵抗指数(HOMA-IR)显著降低(P<0.05),以上结果表明,重组腺病毒Ad-adipsin可以有效改善2型糖尿病模型ZDF大鼠的糖、脂质代谢紊乱,对大鼠2型糖尿病发生发展具有一定的保护效果。

关键词: adipsin, ZDF大鼠, 2型糖尿病

Abstract:

Adipsin is one of the most abundant and specifically expressed adipose proteins and plays pivotal roles in energy homeostasis and systemic metabolism as a circulating factor linking fat cells and obesity to β cell function. To evaluate whether treatment with adipsin could prevent the metabolic abnormalities associated with diabetes and obesity, we examined the effects of overexpression of adenoviral-mediated adipsin (Ad-adipsin) in hyperlipidemic type 2 diabetic rats. Type 2 diabetic rats (n=5) were administered intravenously with Ad-adipsin. Overexpression of adipsin significantly reduced serum resistin, fasting blood glucose (FPG) levels, fasting insulin value(FINS), total serum cholest(TC), triglyceride(TG), and low density lipoprotein(LDL) on the 7th day after treatment (P<0.05). In addition, glucose tolerance and insulin sensitivity were markedly increased (P<0.05). These results indicated that the treatment with Ad-adipsin improves glucose and fat metabolism in type 2 diabetic rats.

Key words: adipsin, ZDF rat, type 2 diabetes