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溃疡性结肠炎和家族性腺瘤性息肉病患者的回肠袋中存在自噬标志物的调节。

Ileal pouch of ulcerative colitis and familial adenomatous polyposis patients exhibit modulation of autophagy markers.

机构信息

IBD Research Laboratory, Coloproctology Unit, Surgery Department University of Campinas (UNICAMP), Medical School, Sao Paulo, Brazil.

Laboratory of Metabolic Disorders, Faculty of Applied Sciences University of Campinas (UNICAMP), Sao Paulo, Brazil.

出版信息

Sci Rep. 2018 Feb 8;8(1):2619. doi: 10.1038/s41598-018-20938-5.

Abstract

Total retocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgery of choice for patients with ulcerative colitis (UC) that are refractory to clinical treatment. Pouchitis is one of the most common complications after this procedure. Defects in autophagy have been reported in inflammatory bowel diseases. However, there are no studies on the IP. Therefore, we studied markers for autophagy in the IP mucosa of UC and FAP patients comparing them to controls with a normal distal ileum. Sixteen patients with IP in "J" shape, asymptomatic and with endoscopically normal IP were evaluated. The control group consisted of eight patients with normal colonoscopy. There was a significant decrease in the transcriptional levels of ATG5, MAP1LC3A and BAX in the FAP group. There was also a decrease in the protein level of Beclin-1 in the UC and FAP compared to the control group. Although the LC3II levels by immunoblot were higher in the UC group, LC3/p62 co-localization were lower in the immunofluorescence analysis in the UC and FAP compared to the control group. Corroborating these results, there was an increase of p62 by immunoblot in the UC group. These findings indicated a modulation of macroautophagy markers in the IP, which may explain the mucosa inflammation predisposition.

摘要

全结肠切除回肠贮袋肛管吻合术(IPAA)是对经临床治疗无效的溃疡性结肠炎(UC)患者的首选手术。 pouchitis 是该手术后最常见的并发症之一。在炎症性肠病中已经报道了自噬的缺陷。然而,对于 IP 尚无相关研究。因此,我们研究了 UC 和 FAP 患者的 IP 黏膜中的自噬标志物,并将其与具有正常远端回肠的对照组进行比较。评估了 16 例具有“J”形 IP 且无症状和内镜下正常 IP 的患者。对照组由 8 例结肠镜检查正常的患者组成。FAP 组 ATG5、MAP1LC3A 和 BAX 的转录水平显著降低。与对照组相比,UC 和 FAP 组的 Beclin-1 蛋白水平也降低。虽然 UC 组的 LC3II 水平通过免疫印迹更高,但在 UC 和 FAP 的免疫荧光分析中 LC3/p62 共定位较低。与这些结果一致,UC 组的 p62 通过免疫印迹增加。这些发现表明 IP 中的自噬标志物发生了调节,这可能解释了黏膜炎症的易感性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2385/5805688/3679873a918a/41598_2018_20938_Fig1_HTML.jpg

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