Arabacı Tamer Sevil, Akbulut Selin, Erdoğan Ömer, Çevik Özge, Ercan Feriha, Yeğen Berrak Ç
Department of Physiology, Marmara University School of Medicine, Basibüyük Mah. Maltepe Basibüyük Yolu No. 9/1, Maltepe, 34854, Istanbul, Turkey.
Department of Physiology, Sakarya University School of Medicine, Sakarya, Turkey.
Dig Dis Sci. 2023 Jun;68(6):2441-2453. doi: 10.1007/s10620-022-07811-2. Epub 2023 Jan 11.
The novel peptide neuropeptide W (NPW) was originally shown to function in the control of feeding behavior and energy homeostasis. The aim of this study was to elucidate the putative preventive and therapeutic effects of NPW on colitis-associated oxidative injury and the underlying mechanisms for its action.
Sprague-Dawley rats in the acute colitis groups received NPW (0.5, 1 or 5 µg/kg/day) injections prior to induction of colitis with acetic acid, while the chronic colitis groups were treated after the induction of colitis. In both acute and chronic colitis (CC) groups, treatments were continued for 5 days and the rats were decapitated at the 24th hour of the last injections and colon tissues were collected for assessments.
NPW pretreatment given for 5 days before colitis induction, as well as treating rats with NPW during the 5-day course of CC, abolished colonic lipid peroxidation. NPW treatment prevented colitis-induced reduction in blood flow, diminished neutrophil infiltration, and pro-inflammatory cytokine responses. NPW pretreatment only at the higher dose reduced colonic edema and microscopic score and preserved colonic glutathione stores. Elevations in cyclooxygenase (COX) enzyme activity and COX-1 protein level during the acute phase of colitis as well as reduction in COX-2 were all reversed with NPW pretreatment. In contrast, NPW treatment was effective in reducing the elevated COX-2 concentration during the chronic phase.
NPW alleviates acetic acid-induced oxidative colonic injury in rats through the upregulation of colonic blood flow as well as the inhibition of COX-2 protein expression and pro-inflammatory cytokine production.
新型肽神经肽W（NPW）最初被证明在控制摄食行为和能量稳态中发挥作用。本研究的目的是阐明NPW对结肠炎相关氧化损伤的潜在预防和治疗作用及其作用的潜在机制。
急性结肠炎组的Sprague-Dawley大鼠在用乙酸诱导结肠炎之前接受NPW（0.5、1或5μg/kg/天）注射，而慢性结肠炎组在诱导结肠炎后进行治疗。在急性和慢性结肠炎（CC）组中，治疗持续5天，并在最后一次注射后24小时将大鼠断头，收集结肠组织进行评估。
在结肠炎诱导前5天给予NPW预处理，以及在CC的5天疗程中用NPW治疗大鼠，均可消除结肠脂质过氧化。NPW治疗可预防结肠炎引起的血流减少，减少中性粒细胞浸润和促炎细胞因子反应。仅高剂量的NPW预处理可减轻结肠水肿和显微镜评分，并保留结肠谷胱甘肽储备。NPW预处理可逆转结肠炎急性期环氧合酶（COX）酶活性和COX-1蛋白水平的升高以及COX-2的降低。相比之下，NPW治疗在降低慢性期升高的COX-2浓度方面有效。
NPW通过上调结肠血流以及抑制COX-2蛋白表达和促炎细胞因子产生，减轻大鼠乙酸诱导的氧化结肠损伤。
