Please wait a minute...

中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2018, Vol. 38 Issue (5): 17-23    DOI: 10.13523/j.cb.20180503
研究报告     
纳米复合肽SCM的制备及其对II型糖尿病治疗作用的研究 *
党诗莹,马义(),文涛,肖兴,洪岸
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 510632
Preparation of Nanometer Composite Peptide SCM and Its Therapeutic Effect on Type II Diabetes
Shi-ying DANG,Yi MA(),Tao WEN,Xing XIAO,An HONG
Department of Cell Biology of Jinan University, Institute of Biological Medicine of Jinan University,Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Center of Genetic Medicine, Guangzhou 510632, China
 全文: PDF(763 KB)   HTML
摘要：

一种新型的神经内分泌肽,垂体腺苷酸环化酶激活肽(PACAP)被发现在碳水化合物或脂质代谢中具有重要作用,但是易受二肽基肽酶IV的降解。将壳聚糖修饰的纳米硒(SeNPs-CTS, SC)作为载体,通过酰胺键负载连接PACAP衍生肽MPL-2,制备稳定性良好、具有协同治疗II型糖尿病作用的纳米复合肽SeNPs-CTS-MPL-2(SCM)。实验结果表明,成功构建了高稳定性的纳米复合肽SCM,SCM的平均粒径为158nm,粒径较为集中, 表面Zeta电位为35.6mV,较SC粒径及Zeta电位有明显的变化,说明MPL-2成功的连接到了SC表面。SCM在水溶液中可稳定存在40天,在水溶液中有较强的稳定性。体外缓释实验表明SCM在48h内不断释放活性多肽MPL-2,有效的延长了MPL-2的作用时间。Ⅱ型糖尿病模型鼠(db/db 小鼠)腹腔注射SCM,葡萄糖耐量实验结果表明MPL-2负载到载体SC上构建了SCM后,SCM在体内不断缓释MPL-2,延长了MPL-2的作用时间,增强了MPL-2的药效。在8周连续用药治疗的过程中,SCM可显著提高II型糖尿病模型小鼠的胰岛素敏感性,药效明显强于MPL-2和SC单独用药。构建了纳米复合肽SCM,可有效的延长MPL-2的作用时间,发挥治疗II型糖尿病的生物学作用。
关键词： 垂体腺苷酸环化酶激活肽衍生肽(MPL-2);  纳米硒;  II型糖尿病;  胰岛素敏感性葡萄糖耐量    
Abstract:

A new type of neuroendocrine peptide, pituitary adenylate cyclase activating peptide (PACAP), has been found to play an important role in carbohydrate or lipid metabolism but is susceptible to dipeptidyl peptidase IV degradation. Chitosan-modified nano-selenium (SeNPs-CTS, SC) was used as a carrier and the PACAP-derived peptide MPL-2 was loaded by amide bond to prepare a stable and stable nanoparticle peptide SeNPs- CTS-MPL-2 (SCM). The experimental results show that the high stability nano-composite peptide SCM was successfully constructed. The average particle diameter of SCM was 158nm, the particle size was relatively concentrated, and the surface Zeta potential was 35.6mV, which was significantly different from the SC particle size and Zeta potential. These proved that MPL-2 successfully connected to the SC surface. SCM was stable in aqueous solution for 40 days and has strong stability in aqueous solution. In vitro sustained release experiments showed that SCM released MPL-2 continuously within 48 hours, effectively prolonging the action time of MPL-2. Type 2 diabetes model mice (db/db mice) were injected intraperitoneally with SCM. Glucose tolerance test results showed that SCM sustained release of MPL-2 in vivo after MPL-2 was loaded onto carrier SC, prolonged the effect time of MPL-2 and enhanced the efficacy of MPL-2. During 8 weeks of continuous medication, SCM significantly increased insulin sensitivity in mice with type 2 diabetes mellitus, significantly more potent than MPL-2 and SC alone. The nanocomposite peptide SCM was constructed to effectively prolong the action time of MPL-2 and to exert the biological effect of treating type II diabetes.
Key words: Pituitary adenylate cyclase-activating peptide-derived peptide (MPL-2)    Nano selenium Type    II diabetes    Insulin sensitivity glucose tolerance
收稿日期: 2018-01-19 出版日期: 2018-06-05
ZTFLH:  Q819  
基金资助: * 国家自然科学基金(81373314);国家自然科学基金(81741130);广东省自然科学基金(2015A030313333);广州市科技计划资助项目(201707010245);广州市科技计划资助项目(201704020117)
通讯作者: 马义     E-mail: tmayi@jnu.edu.cn
服务　　
把本文推荐给朋友
加入引用管理器
E-mail Alert
RSS
作者相关文章　　
党诗莹
马义
文涛
肖兴
洪岸

引用本文:

党诗莹,马义,文涛,肖兴,洪岸. 纳米复合肽SCM的制备及其对II型糖尿病治疗作用的研究 *[J]. 中国生物工程杂志, 2018, 38(5): 17-23.

Shi-ying DANG,Yi MA,Tao WEN,Xing XIAO,An HONG. Preparation of Nanometer Composite Peptide SCM and Its Therapeutic Effect on Type II Diabetes. China Biotechnology, 2018, 38(5): 17-23.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.20180503    或    https://manu60.magtech.com.cn/biotech/CN/Y2018/V38/I5/17

图1  粒径、表面Zeta电位及粒径稳定性
图2  SCM体外缓释,SCM可持续释放48h
图3  db/db小鼠的腹腔内注射葡萄糖耐量试验
图4  连续用药8周db/db小鼠的胰岛素耐量实验
[1] Miyata A, Arimura A, Dahl R R , et al. Isolation of a novel 38 residue-hypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells. Biochem Biophys Res Commun, 1989,164(1):567-574.
doi: 10.1016/0006-291X(89)91757-9 pmid: 2803320
[2] Ghzili H, Grumolato L, Thouennon E , et al. Role of PACAP in the physiology and pathology of the sympathoadrenal system. Front Neuroendocrinol, 2008,29(1):128-141.
doi: 10.1016/j.yfrne.2007.10.001 pmid: 18048093
[3] Yon L, Alexandre D, Montero M , et al. Pituitary adenylate cyclase-activating polypeptide and its receptors in amphibians. Microsc Res Tech, 2001,54(3):137-157.
doi: 10.1002/jemt.1129 pmid: 11458398
[4] Yon L, Breault L, Contesse V , et al. Pituitary adenylate cyclase-activating polypeptide receptors in the fetal human adrenal gland. Ann N Y Acad Sci, 1998,865(1):416-419.
doi: 10.1111/j.1749-6632.1998.tb11207.x pmid: 9928041
[5] Pirger Z, Laszlo Z, Hiripi L , et al. Pituitary adenylate cyclase activating polypeptide (PACAP) and its receptors are present and biochemically active in the central nervous system of the pond snail Lymnaea stagnalis. J Mol Neurosci, 2010,42(3):464-471.
doi: 10.1007/s12031-010-9361-x pmid: 20396976
[6] Vaudry D, Falluel-Morel A, Bourgault S , et al. Pituitary adenylate cyclase-activating polypeptide and its receptors: 20 years after the discovery. Pharmacol Rev, 2009,61(3):283-357.
doi: 10.1124/pr.109.001370
[7] Lee J C, Cho Y J, Kim J , et al. Region-specific changes in the immunoreactivity of vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide receptors (VPAC2, and PAC1 receptor) in the aged rat brains. Brain Res, 2010,1351(1):32-40.
doi: 10.1016/j.brainres.2010.06.048
[8] Pan C Q, Li F, Tom I , et al. Engineering novel VPAC2-selective agonists with improved stability and glucose-lowering activity in vivo. J Pharmacol Exp Ther, 2007,320(2):900-906.
doi: 10.1124/jpet.106.112276 pmid: 17110523
[9] Joo K M, Chung Y H, Kim M K , et al. Distribution of vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide receptors (VPAC1, VPAC2, and PAC1 receptor) in the rat brain. J Comp Neurol, 2004,476(4):388-413.
doi: 10.1002/cne.20231 pmid: 15282712
[10] Alexandre D, Anouar Y, Jegou S , et al. A cloned frog vasoactive intestinal polypeptide/pituitary adenylate cyclase-activating polypeptide receptor exhibits pharmacological and tissue distribution characteristics of both VPAC1 and VPAC2 receptors in mammals. Endocrinology, 1999,140(3):1285-1293.
doi: 10.1210/endo.140.3.6576
[11] Wang D H, Ma Y, Han L , et al. Preparation of novel recombinant PACAP derivative MPL-2 and its effect on anti-type 2 diabetes melitus. Journal of Chinese Biotechnology, 2017,37(5):59-65.
[12] Papp L V, Lu J, Holmgren A , et al. From selenium to selenoproteins: Synthesis, identity, and their role in human health. Antioxidants & Redox Signaling, 2007,9(7):775-806.
doi: 10.1089/ars.2007.1528 pmid: 17508906
[13] Benstoem C, Goetzenich A, Kraemer S , et al. Selenium and its supplementation in cardiovascular disease-what do we know. Nutrients, 2015,7(5):3094-3118.
doi: 10.3390/nu7053094 pmid: 4446741
[14] Rao L, Ma Y, Zhuang M J , et al. Chitosan-decorated selenium nanoparticles as protein carriers to improve the in vivo half-life of the peptide therapeutic BAY 55-9837 for type 2 diabetes mellitus. International Journal of Nanomedicine, 2014,9(1):4819-4828.
doi: 10.2147/IJN.S67871 pmid: 4207575
[15] Kumar G S, Kulkarni A, Khurana A , et al. Selenium nanoparticles involve HSP-70 and SIRT1 in preventing the progression of type 1 diabetic nephropathy. Chemico-biological Interactions, 2014,223(5):125-133.
doi: 10.1016/j.cbi.2014.09.017 pmid: 25301743
[16] Rayman M P . Selenium and human health. The Lancet, 2012,379(9822):1256-1268.
doi: 10.1016/S0140-6736(11)61452-9
[17] 童春义 . 基于硒纳米颗粒的新型生物材料研制与表征方法研究. 长沙: 湖南大学, 2008.
doi: 10.7666/d.y1448984
Tong C Y . Development and characterization of novel biological materials based on selenium nanoparticles. Changsha: Hunan University. 2008.
doi: 10.7666/d.y1448984
[18] Liu W, Li X L, Wong Y S , et al. Selenium nanoparticles as a carrier of 5-fluorouracil to achieve anticancer synergism. Acs Nano, 2012,6(8):6578-6591.
doi: 10.1021/nn202452c
[19] Iizuka Y, Sakurai E, Hikichi N . Effects of selenium on the serum glucose and insulin levels in diabetic rats. Nihon Yakurigaku Zasshi Folia Pharmacologica Japonica, 1992,100(2):151-156.
doi: 10.1254/fpj.100.151 pmid: 1427498
[20] Stapleton S R . Selenium: an insulin-mimetic. Cellular and Molecular Life Sciences: CMLS, 2000,57(13-14):1874-1879.
doi: 10.1007/PL00000669
[1] 林敏. 玉米生物育种基础研究与关键技术[J]. 中国生物工程杂志, 2021, 41(12): 1-3.
[2] 吴函蓉,王莹,黄英明,李冬雪,李治非,方子寒,范玲. 以基地平台为抓手,促进生物技术创新与转化[J]. 中国生物工程杂志, 2021, 41(12): 141-147.
[3] 尹泽超,王晓芳,龙艳,董振营,万向元. 玉米穗腐病抗性鉴定、遗传分析与分子机制*[J]. 中国生物工程杂志, 2021, 41(12): 103-115.
[4] 冷燕,孙康泰,刘倩倩,蒲阿庆,李翔,万向元,魏珣. 全球基因编辑作物监管趋势研究[J]. 中国生物工程杂志, 2021, 41(12): 24-29.
[5] 何伟,祝蕾,刘欣泽,安学丽,万向元. 玉米遗传转化与商业化转基因玉米开发*[J]. 中国生物工程杂志, 2021, 41(12): 13-23.
[6] 杨梦冰,江易林,祝蕾,安学丽,万向元. CRISPR/Cas植物基因组编辑技术及其在玉米中的应用*[J]. 中国生物工程杂志, 2021, 41(12): 4-12.
[7] 殷芳冰,王成,龙艳,董振营,万向元. 玉米雌穗性状遗传分析与形成机制*[J]. 中国生物工程杂志, 2021, 41(12): 30-46.
[8] 秦文萱,刘鑫,龙艳,董振营,万向元. 玉米叶夹角形成的遗传基础与分子机制解析*[J]. 中国生物工程杂志, 2021, 41(12): 74-87.
[9] 王锐璞,董振营,高悦欣,龙艳,万向元. 玉米籽粒淀粉含量遗传基础与调控机制*[J]. 中国生物工程杂志, 2021, 41(12): 47-60.
[10] 马雅杰,高悦欣,李依萍,龙艳,董振营,万向元. 玉米株高和穗位高的遗传基础与分子机制*[J]. 中国生物工程杂志, 2021, 41(12): 61-73.
[11] 王彦博,魏佳,龙艳,董振营,万向元. 玉米雄穗性状遗传结构与形成分子机制*[J]. 中国生物工程杂志, 2021, 41(12): 88-102.
[12] 毛开云,李荣,李丹丹,赵若春,范月蕾,江洪波. 全球双特异性抗体药物研发格局分析*[J]. 中国生物工程杂志, 2021, 41(11): 110-118.
[13] 吴函蓉,王莹,杨力,葛瑶,范玲. 我国生物技术基地平台现状与发展建议[J]. 中国生物工程杂志, 2021, 41(11): 119-123.
[14] 刘天义,冯卉,SALSABEELYousuf,解领丽,苗向阳. lncRNA在动物脂肪沉积中的研究进展*[J]. 中国生物工程杂志, 2021, 41(11): 82-88.
[15] 薛志勇,代红生,张显元,孙艳颖,黄志伟. 表达透明颤菌血红蛋白基因对酿酒酵母生长及细胞内氧化状态的影响*[J]. 中国生物工程杂志, 2021, 41(11): 32-39.
主管：中国科学院 　主办：中国科学院文献情报中心 　中国生物技术发展中心 　中国生物工程学会