Triptolide exerts protective effects against fibrosis following ileocolonic anastomosis by mechanisms involving the miR-16-1/HSP70 pathway in IL-10-deficient mice.
Int J Mol Med
; 40(2): 337-346, 2017 Aug.
Article
em En
| MEDLINE
| ID: mdl-28627592
ABSTRACT
Surgeries, particularly ileocecal resection (ICR), are often required in the treatment of Crohn's disease (CD). However, recurrences are common for patients who undergo ICR, and anastomotic fibrosis is the main cause of re-operation. The present study aimed to investigate the therapeutic effects of triptolide (TPL) in ameliorating fibrosis following ileocolonic anastomosis. A model of IL10/ mice undergoing ICR was used to study postsurgical inflammation and fibrosis of anastomosis. For this purpsose, interleukin (IL)10/ mice were randomly divided into 3 groups as follows the control group, the salinetreated group subjected to ICR (STICR) and the TPLtreated group subjected to ICR (TTICR). Wildtype (WT) mice of matching ages were assigned to the WT group. The effects of TPL treatment on ileocolonic anastomosis were determined by histopathological evaluation, western blot analysis and ELISA. The analysis of the effects of TPL treatment on microRNA161 (miR161) and heat shock protein 70 (HSP70) expression was carried out by RTqPCR and western blot analysis. Compared with the control group, significantly higher inflammation scores following anastomosis were observed in the STICR group (P<0.05), although reversion was observed in the TTICR group, which was consistent with changes in the area of CD4+ cell infiltration. The elevated fibrosis scores and the overexpression of procollagen I and III in the STICR group were all inhibited by TPL. With an increase in the severity of inflammation and fibrosis, the levels of IL6, tumor necrosis factorα (TNFα) and transforming growth factorß1 (TGFß1) increased; however, a significant decrease in these levels was observed following treatment with TPL (P<0.05). The results of RTqPCR revealed that the upregulated miR161 levels in the STICR group were significantly reduced by TPL. HSP70, which can be inhibited by miR-16-1, ameliorates anastomotic inflammation and fibrosis. Thus, the present study demonstrates that TPL exerts a protective effect against fibrosis following anastomosis in CD. The miR161/HSP70 signaling pathway, which can be regulated by TPL, may thus represent a novel therapeutic option in CD that deserves further investigation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fenantrenos
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Complicações Pós-Operatórias
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Anastomose Cirúrgica
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Interleucina-10
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Proteínas de Choque Térmico HSP70
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Substâncias Protetoras
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MicroRNAs
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Diterpenos
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Intestinos
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article