新型基因重组PACAP衍生物MPL-2的制备及其抗2型糖尿病作用研究

发布时间：2018-03-19 11:06

本文选题：基因工程　切入点：垂体腺苷酸环化酶激活肽衍生物　出处：《中国生物工程杂志》2017年05期 　论文类型：期刊论文

【摘要】：利用基因工程技术高效制备具有治疗2型糖尿病功能的垂体腺苷酸环化酶激活肽(PACAP)衍生物MPL-2,并以2型糖尿病小鼠(db/db小鼠)为模型在体内研究其抗2型糖尿病的生物学作用。实验结果表明:利用基因工程技术制备的PACAP27衍生多肽MPL-2的分子质量为3 902Da.,纯度达97%,其产率可达29.3mg/L发酵产物;在以db/db小鼠为模型的体内葡萄糖耐量实验中,MPL-2可有效促进小鼠胰岛素第一时相(5~15min)分泌,显著提高小鼠的葡萄糖耐受能力。在MPL-2的长效药效学实验中,经过8周连续用药治疗后,MPL-2可显著提高db/db小鼠的胰岛素敏感性,胰岛素耐量实验60min时MPL-2可将小鼠血糖降至初始值的63.52%;同时,在8周连续用药治疗过程中,与生理盐水(NS)处理组相比,MPL-2可有效降低db/db小鼠的体重、空腹血糖、饮食量、饮水量,分别低于NS组21.98%、21.46%、22.20%、60.07%,而且可显著改善db/db小鼠的血脂常数,生物学作用显著优于多肽BAY55-9837。建立了新型基因重组PACAP27衍生多肽MPL-2的高效制备技术,重组多肽MPL-2可有效改善2型糖尿病db/db小鼠的葡萄糖耐量、胰岛素敏感性、血脂常数,显著降低db/db小鼠的体重、空腹血糖、饮食和饮水量,从而发挥治疗2型糖尿病的生物学作用,可为MPL-2的药用研发提供实验数据。
[Abstract]:Efficient preparation of pituitary adenylate cyclase activating peptide PACAP derivative MPL-2 with gene engineering technique and its antidiabetic effect in vivo in mice with type 2 diabetes mellitus. The results showed that the molecular weight of PACAP27 derived polypeptide MPL-2 was 3 902Da. the purity was 97% and the yield was 29.3mg / L. In the glucose tolerance test of db/db mice in vivo, MPL-2 could effectively promote the secretion of insulin in mice at the first phase (5min), and significantly improve the glucose tolerance ability of mice. In the long-acting pharmacodynamics test of MPL-2, MPL-2 could improve the glucose tolerance of mice. After 8 weeks of continuous treatment, MPL-2 could significantly improve the insulin sensitivity of db/db mice, and MPL-2 could reduce the blood glucose to 63.52% of the initial value at 60 min after insulin tolerance test, meanwhile, during 8 weeks of continuous treatment, MPL-2 could reduce the blood glucose to 63.52% of the initial value. Compared with NS treatment group, MPL-2 significantly decreased the body weight, fasting blood glucose, diet and drinking water of db/db mice, which were lower than those in NS group 21.98 and 21.46 and 22.20%, respectively, and could significantly improve the blood lipid constant of db/db mice. The biological effect was significantly better than that of BAY55-9837.The high efficiency preparation technique of novel recombinant PACAP27 derived polypeptide MPL-2 was established. The recombinant polypeptide MPL-2 could effectively improve the glucose tolerance, insulin sensitivity and blood lipid constant of db/db mice with type 2 diabetes mellitus. Db/db mice were significantly reduced in body weight, fasting blood glucose, diet and drinking water, so as to play a biological role in the treatment of type 2 diabetes, which could provide experimental data for the medical research and development of MPL-2.
【作者单位】：暨南大学细胞生物学系暨南大学生物医药研究院广东省生物工程药物重点实验室基因工程药物国家工程研究中心;广州中医药大学第二附属医院(广东省中医院);
【基金】：国家自然科学基金项目(81373314) 广东省自然科学基金项目(2015A030313333,2015A030313345) 广东省科技计划项目(2014A020210015,2013B090500105) 中央高校基本科研业务费专项资金(21615412)资助项目
【分类号】：R943;R96

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