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Therapeutic effects of different doses of polyethylene glycosylated porcine glucagon-like peptide-2 on ulcerative colitis in male rats

文献类型： 外文期刊

作者： Qi, Ke-ke 1 ; Lv, Jia-jia 1 ; Wu, Jie 1 ; Xu, Zi-wei 1 ;

作者机构： 1.Zhejiang Acad Agr Sci, Inst Anim Sci, 198 Shiqiao Rd, Hangzhou 310021, Zhejiang, Peoples R China

关键词： Porcine glucagon-like peptide-2;Ulcerative colitis;Tight junction;Inflammation cytokines

期刊名称：BMC GASTROENTEROLOGY （ 影响因子：3.067； 五年影响因子：3.441 ）

ISSN： 1471-230X

年卷期： 2017 年 17 卷

页码：

收录情况： SCI

摘要： Background: Polyethylene glycosylated (PEGylated) porcine glucagon-like peptide-2 (pGLP-2) considerably increases half-life and stability compared with the native pGLP-2, but the effective dose for intestinal damage is still unclear. This study aims to evaluate the available dose of polyethylene glycosylated porcine glucagon-like peptide-2 (PEG-pGLP-2), a modified, long-acting form of pGLP-2 in an experimental rat model of ulcerative colitis. Methods: Thirty-five male rats were randomly assigned into five groups: control, dextran sodium sulphate (DSS), DSS + PEG-pGLP-2(L), DSS + PEG-pGLP-2(M) and DSS + PEG-pGLP-2(H). Rats in control group received only water; other rats were fed with 5% (w/ v) DSS and intraperitoneally administered with 12.5, 25 and 100 nmol/ kg PEG-pGLP-2 daily for 6 days. Results: Compared with the control treatment, DSS treatment significantly (p < 0.05) decreased body weight change, colonic length, duodenal villus height and expression of zonula occludens-1, whereas significantly (p < 0.05) increased colonic damage score and expression of claudin-1, interleukin (IL)-1, IL-7, IL-10, interferon-. and tumour necrosis factor (TNF)-a in colon. However, the three doses of PEG-pGLP-2 all reduced these effects; these treatments significantly (p < 0.05) increased body weight change and duodenal villus height, whereas significantly (p < 0.05) decreased colonic damage score and expression of IL-1, IL-7 and TNF-a in colon. Specifically, low-dose (12.5 nmol/ kg/ d) PEG-pGLP-2 was effective. Conclusions: These results indicated that PEG-pGLP-2 is a novel and potentially effective therapy for intestinal healing in a relatively low dose.

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[1]Glucagon-like peptide-2-loaded microspheres as treatment for ulcerative colitis in the murine model. Wu, Jie,Qi, Keke,Xu, Ziwei,Wan, Jin. 2015

[2]Porcine glucagon-like peptide-2 microspheres ameliorate inflammation in lipopolysaccharide-challenged weaning piglets. Wu, J.,Qi, K. K.,Xu, Z. W..

[3]Purified PEGylated porcine glucagon-like peptide-2 reduces the severity of colonic injury in a murine model of experimental colitis. Qi, Ke-ke,Wu, Jie,Wan, Jing,Men, Xiao-ming,Xu, Zi-wei.

[4]Effect of porcine glucagon-like peptides-2 on tight junction in GLP-2R+IPEC-J2 cell through the PI(3)k/Akt/mTOR/p70(S6K) signalling pathway. Qi, K. K.,Sun, Y. Q.,Wan, J.,Deng, B.,Men, X. M.,Wu, J.,Xu, Z. W..

[5]PEGylated porcine glucagon-like peptide-2 improved the intestinal digestive function and prevented inflammation of weaning piglets challenged with LPS. Qi, K. K.,Wu, J.,Deng, B.,Li, Y. M.,Xu, Z. W..

[6]Effects of PEGylated porcine glucagon-like peptide-2 therapy in weaning piglets challenged with lipopolysaccharide. Qi, Ke-ke,Wu, Jie,Xu, Zi-wei.

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