摘要
本试验旨在研究猪胰高血糖素样肽-2(p[Gly2]GLP-2)、聚乙二醇修饰猪胰高血糖素样肽2(PEG-p[Gly2]GLP-2)和p[Gly2]GLP-2微球在大鼠体内的药代动力学过程,为利用p[Gly2]GLP-2修复断奶仔猪肠道损伤提供参考依据。选取18只280 g左右的雄性SD大鼠,随机分为3组,分别单次皮下注射p[Gly2]GLP-2(5.64 nmol/kg)、PEG-p[Gly2]GLP-2(5.64 nmol/kg)和p[Gly2]GLP-2微球(15 mg/只),定点采血后,酶联免疫吸附测定(ELISA)法测定胰高血糖素样肽-2(GLP-2)的血药浓度。结果表明:1)PEG-p[Gly2]GLP-2的半衰期(t1/2)是p[Gly2]GLP-2的4倍,血药浓度-时间曲线下面积(AUC0-t)和平均滞留时间(MRT0-t)是p[Gly2]GLP-2的3倍,清除率(CL)是p[Gly2]GLP-2的1/2,两者的达峰浓度(Cm ax)相差不大,PEG-p[Gly2]GLP-2的达峰时间(Tm ax)滞后于p[Gly2]GLP-2。2)p[Gly2]GLP-2微球的达峰时间与p[Gly2]GLP-2、PEG-p[Gly2]GLP-2相差不大,但半衰期为(72.20±6.02)h,平均滞留时间为(90.66±7.41)h。结果提示,经聚乙二醇(PEG)修饰后p[Gly2]GLP-2的药代动力学行为发生了很大的改变,半衰期延长、达峰时间滞后、平均滞留时间延长、血浆清除减慢、生物利用度更高;p[Gly2]GLP-2微球半衰期更长,且持续稳定的释放,操作便利。
This study aimed to analyze the pharmacokinetics of porcine glucagon-like peptide-2 [Gly2]（p[Gly2]GLP-2）,PEGylated porcine glucagon-like peptide-2[Gly2]（PEG-p[Gly2]GLP-2） and p[Gly2]GLP-2 microspheres in rats,in order to provide references for the repairation of intestinal injury of weaned pigs by p[Gly2]GLP-2.Eighteen Sprague-Dawley（SD） male rats with 280 g body weight were randomly divided into 3 groups,which were p[Gly2]GLP-2 group（single subcutaneous administration of 5.64 nmol/kg p[Gly2]GLP-2）,PEG-p[Gly2]GLP-2 group（single subcutaneous administration of 5.64 nmol/kg PEG-p[Gly2]GLP-2） and p[Gly2]GLP-2 microspheres group（single subcutaneous administration of 15 mg microspheres per rat）.After blood sampled,plasma drug concentration of GLP-2 was determined by enzyme linked immunosorbent assay（ELISA）.The results showed as follows：1） compared to p[Gly2]GLP-2,PEG-p[Gly2]GLP-2 increased the half-life（t1/2） by 4-fold,and increased the mean residence time（MRT0-t） and the area under the curve（AUC0-t） by 3-fold,but decreased the clearance（CL） to a half.The peak concentration（Cm ax） was similar between two drugs,but peak time（Tm ax） of PEG-p[Gly2]GLP-2 was later than p[Gly2]GLP-2.2） The half time of p[Gly2]GLP-2 microspheres was（72.20 ± 6.02） h and mean residence time was（90.66 ± 7.41） h,but peak time was similar with p[Gly2]GLP-2 and PEG-p[Gly2]GLP-2.These results showthat PEG-p[Gly2]GLP-2 greatly improve the pharmacological profiles,increase half time,peak time and mean residence time,decrease clearance rate and improve bioavailability.p[Gly2]GLP-2 microspheres with a longer half-life are released sustained and stable,and operated easily.
出处
《动物营养学报》
CAS
CSCD
北大核心
2016年第8期2650-2656,共7页
CHINESE JOURNAL OF ANIMAL NUTRITION
基金
现代农业产业技术体系(CARS-36)
浙江省自然科学基金项目(LY15C170002)
