Vasoactive Intestinal Peptide protects mitochondria against the detrimental effects of TNFα and IFNγ induced during Citrobacter rodentium infection with partial alleviation of colitis

A. Maiti, S. Lindén
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Abstract

To directly assess the therapeutic effect of vasoactive intestinal peptide (VIP) in ameliorating the IFNγ and TNFα induced mitochondrial dysfunction in colitis affected colon epithelial cells utilizing Citrobacter rodentium induced murine model.Every C57BL/6 mice receiving 100 µl of C. rodentium strain ICC169 (5 x 109 CFU) by single oral-gavage were sacrificed on day 14 post-infection. Infected mice were divided into 3 groups for VIP treatment (0.5 nmol/mouse/day) – Group I: day 5 to 10, Group II: day 5 to 14, Group III: day 10 to 14. Colon samples collected were utilized for study of mitochondrial functional parameters and histopathological features of colitis. Therapeutic impact of VIP on mitochondrial dysfunction was better observed in Group I mice compared to other groups. The VIP treatment partially alleviated decreased activities of complex I and IV, restored mitochondrial phosphorylation capacity, mitochondrial transmembrane potential and ATP loss. However, VIP was less effective in ameliorating histopathological features of colitis.
血管活性肠肽保护线粒体免受鼠柠檬酸杆菌感染诱导的TNFα和IFNγ的有害影响,部分缓解结肠炎
利用鼠Citrobacter rodentium诱导的小鼠模型,直接评价血管活性肠肽(vasoactive intestinal peptide, VIP)对IFNγ和TNFα诱导的结肠炎结肠上皮细胞线粒体功能障碍的改善作用。每只C57BL/6小鼠经单次灌胃接种5 × 109 CFU (C. rodentium strain ICC169) 100µl后,于感染后第14天处死。将感染小鼠分为3组(0.5 nmol/只/天)进行VIP治疗:第1组:第5 ~ 10天,第2组:第5 ~ 14天,第3组:第10 ~ 14天。收集结肠样本用于研究结肠炎的线粒体功能参数和组织病理学特征。与其他组相比,VIP对线粒体功能障碍的治疗作用在I组小鼠中得到了更好的观察。VIP处理部分缓解了复合物I和IV活性下降,恢复了线粒体磷酸化能力、线粒体跨膜电位和ATP损失。然而,VIP在改善结肠炎的组织病理学特征方面效果较差。
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