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BMC Gastroenterol ; 17(1): 34, 2017 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-28259136

RESUMO

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-γ and tumour necrosis factor (TNF)-α 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-α 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.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Colo/efeitos dos fármacos , Peptídeo 2 Semelhante ao Glucagon/administração & dosagem , Mucosa Intestinal/efeitos dos fármacos , Polietilenoglicóis/administração & dosagem , Animais , Peso Corporal/efeitos dos fármacos , Claudina-1/efeitos dos fármacos , Colite Ulcerativa/induzido quimicamente , Citocinas/efeitos dos fármacos , Sulfato de Dextrana , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Duodeno/efeitos dos fármacos , Masculino , Ratos , Proteína da Zônula de Oclusão-1/efeitos dos fármacos
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