猪胰高血糖素样肽-2(pGLP-2)微球的制备及其对结肠炎小鼠肠道损伤修复的研究  

Preparation of Porcine(Sus scrofa) Glucagon- like Peptide- 2 Microspheres(pGLP-2) and Its Therapeutic Effect in a Murine(Mus musculus) Model of Colitis

作　　者：吴杰[1] 齐珂珂[1] 徐子伟[1] 万晶[1] 刘淑杰[1] 

机构地区：[1]浙江省农业科学院畜牧兽医研究所,杭州310021

出　　处：《农业生物技术学报》2014年第2期150-157,共8页Journal of Agricultural Biotechnology

基　　金：现代农业产业技术体系(No.CARS-36);国家青年科学基金项目(No.C170105/31101724);浙江省自然科学基金(No.LQ12C17004);浙江省重点科技创新团队项目(No.2010R50027)

摘　　要：胰高血糖素样肽2(glucagon-like peptide-2,GLP-2)能促进肠道生长,提高营养物质的消化吸收,并且对肠道损伤有修复作用。本研究通过对复乳法(water in oil in water,W/O/W)和油包水包固体乳化法(solid in oil in water,S/O/W)两种微球制备方法的比较,选出适合制备猪(Sus scrofa)GLP-2(pGLP-2)微球的方法,并研究其对葡聚糖硫酸钠(dextran sulfate sodium,DSS)致小鼠结肠炎肠道损伤的修复效果。结果表明,W/O/W法制备的微球粒径为(54.19±17.28)μm,包封率为60%,表面有许多裂痕和小孔,突释高达65.1%;S/O/W法制备的微球粒径为(31.17±8.17)μm,包封率为72%,表面光滑圆整,突释为15.58%。体外释放研究表明,S/O/W法制备的pGLP-2微球在体外9 d累计释放59.1%;BALB/C小鼠(Mus musculus)连续饮用3%DSS 7 d成功建立小鼠结肠炎模型,腹腔注射S/O/W法制备的pGLP-2微球(10 mg/只)能够显著缓解DSS引起的体重降低、结肠长度变短和对结肠组织结构的破坏(P<0.05),与DSS组和饮水组相比,显著增加十二指肠的绒毛高度及绒毛高度/隐窝深度比值(P<0.05)。因此S/O/W法制备的pGLP-2微球包封率高,突释低,稳定性好,一次注射就能够很好地修复DSS致小鼠结肠炎的肠道损伤。本研究结果为pGLP-2在断奶仔猪肠道保护或损伤修复中的应用提供实验依据,同时为其在仔猪肠道疾病上的应用提供了基础资料。Glucagon-like peptide-2（GLP-2） can promote the growth of intestine, enhance nutrient absorption and repair intestinal injures. In this study, porcine glucagon-like peptide-2 （pGLP-2） microspheres were prepaired by Water in oil in water（W/O/W）method and solid in oil in water（S/O/W）method. A better one was chosen to investigate the potential therapeutic effects on intestinal injures of colitis in mice（Mus musculus） induced by dextran sulfate sodium （DSS）. The results showed that microspheres prepared by W/O/W method could encapsulate 60% pGLP-2 with （54.19±17.28） μm in diameter while the drug burst was 65.1% and the surface was porous; Microspheres prepared by S/O/W method could encapsulate 72% pGLP-2 with （31.17±8.17） μm in diameter and 15.58% in drug burst. BALB/c mice were inoculated with 3% DSS solution for 7 d to induce colitis successfully. DSS inoculated mice were treated with pGLP-2 microspheres （10 mg per mice） prepared by S/O/W method in the third day. DSS＋pGLP-2 microspheres group significantly decreased body weight loss and colonic damage and increased colon length （P〈0.05）. Villus height and villus height /crypt depth ratio in mice of DSS＋microspheres group significantly increased compared with that of DSS-only inoculated group and water group （P〈0.05）. This study demonstrates pGLP-2 microspheres prepared by S/O/W method had higher encapsulation efficiency, lower drug burst and more stable than that of microspheres prepared by W/O/W method. Administration pGLP-2 microspheres once reduced the severity of colonic injury in murine colitis. The potencies of this product highlight its potential as therapeutic agent for intestinal diseases in piglet.

关 键 词：猪胰高血糖素样肽-2(pGLP-2) 复乳法(W O W) 油包水包固体乳化法(S O W) 微球 结肠炎 小鼠 

分 类 号：S858.287.3[农业科学—临床兽医学]