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通过调节 p38/MSK1 通路抑制 NF-κB 激活,肠外营养可预防炎症性肠病。

Exclusive enteral nutrition protects against inflammatory bowel disease by inhibiting NF‑κB activation through regulation of the p38/MSK1 pathway.

机构信息

Department of Gastroenterology, Gulou School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu 210008, P.R. China.

Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, P.R. China.

出版信息

Int J Mol Med. 2018 Sep;42(3):1305-1316. doi: 10.3892/ijmm.2018.3713. Epub 2018 Jun 4.

Abstract

Although enteral nutrition therapy for inflammatory bowel disease has been confirmed to be an effective treatment method, the exact mechanism responsible for the effects of enteral nutrition remains unclear. The aim of the present study was to investigate the protective effect of exclusive enteral nutrition (EEN) against colitis, and to elucidate the potential mechanisms by inhibiting p65 activation via regulating the p38/mitogen‑ and stress‑activated protein kinase‑1 (MSK1) pathway. Experiments were performed by establishing dextran sulfate sodium (DSS)‑mice colitis and picrylsulfonic acid solution (TNBS)‑induced rat colitis, and the results demonstrated that EEN treatment attenuated body weight loss, colon length shortening and colonic pathological damage caused by colitis. EEN also inhibited inflammatory cells infiltration and decreased myeloperoxidase and inducible nitric oxide synthase activities. Furthermore, EEN significantly reduced the production of pro‑inflammatory mediators in serum and the colon. Mechanically, EEN suppressed activation of p65 by inhibiting the p38/MSK1 pathway. In conclusion, the present study demonstrated that EEN attenuated DSS‑ and TNBS‑induced colitis by inhibiting p65 activation via regulating the p38/MSK1 pathway, thus suggesting that EEN is effective in the treatment of colitis.

摘要

虽然肠内营养治疗炎症性肠病已被证实是一种有效的治疗方法,但肠内营养的确切作用机制尚不清楚。本研究旨在探讨肠内营养(EEN)对结肠炎的保护作用,并通过抑制 p65 激活来阐明其潜在机制,即调节 p38/有丝分裂原和应激激活蛋白激酶 1(MSK1)通路。通过建立葡聚糖硫酸钠(DSS)诱导的小鼠结肠炎和对硝基苯磺酸(TNBS)诱导的大鼠结肠炎进行实验,结果表明 EEN 治疗可减轻结肠炎引起的体重减轻、结肠缩短和结肠病理损伤。EEN 还抑制了炎症细胞浸润,并降低了髓过氧化物酶和诱导型一氧化氮合酶的活性。此外,EEN 还显著降低了血清和结肠中促炎介质的产生。在机制上,EEN 通过抑制 p38/MSK1 通路抑制了 p65 的激活。综上所述,本研究表明 EEN 通过调节 p38/MSK1 通路抑制 p65 的激活,减轻 DSS 和 TNBS 诱导的结肠炎,提示 EEN 对结肠炎的治疗有效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc22/6089761/39e60d260847/IJMM-42-03-1305-g00.jpg

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