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Intestinal dysmotility after bowel resection in rats is associated with decreased ghrelin and vimentin expression and loss of intestinal cells of Cajal
American Journal of Physiology-Gastrointestinal and Liver Physiology ( IF 4.5 ) Pub Date : 2020-12-16 , DOI: 10.1152/ajpgi.00223.2020
Igor Sukhotnik 1, 2 , Yoav Ben-Shahar 1, 3 , Yulia Pollak 1 , Shlomi Cohen 2, 4 , Hadar Moran-Lev 2, 4 , Tal Koppelmann 1 , Migel Gorenberg 3
Affiliation  

The purpose of this study was to evaluate the mechanisms of intestinal motility in a rat model of short bowel syndrome (SBS). Rats were divided into three groups: Sham rats underwent bowel transection; SBS-NSI rats underwent a 75% bowel resection and presented with normal intestinal size (NSI) at sacrifice and hypermotility patterns; SBS-DYS showed dysmotile (DYS) enlarged intestine and inhibited motility patterns. Animals were sacrificed after 2 weeks. Illumina's Digital Gene Expression (DGE) analysis was used to determine the intestinal motility-related gene expression profiling in mucosal samples. Intestinal motility-related and interstitial cells of Cajal (ICC) genes and protein expression in intestinal muscle layer were determined using Real Time PCR, Western blotting and immunohistochemistry. Gastrointestinal tract motility was studied by microcomputer tomography. From ten Ca2+ signaling pathway related genes, six genes in jejunum and seven genes in ileum were down-regulated in SBS vs Sham animals. Down regulation of TMEM16A mRNA and protein was confirmed by Real Time PCR. Rapid intestinal transit time in SBS-NSI rats correlated with mild decrease in TMEM 16A, c-kit and vimentin mRNA and protein expression (vs Sham animals). SBS-DYS rats demonstrated enlarged intestinal loops and delayed small intestinal emptying (on imaging studies) that were correlated with marked down-regulation in TMEM 16A, c-kit, vimentin, ghrelin mRNA and protein levels compared to the other two groups. In conclusion, two weeks following massive bowel resection in rats, impaired intestinal motility was associated with decreased vimentin and ghrelin gene and protein levels as well as loss of ICC (c-kit and TMEM16A).

中文翻译:

大鼠肠切除术后肠动力障碍与生长素释放肽和波形蛋白表达降低以及 Cajal 肠细胞丢失有关

本研究的目的是评估短肠综合征 (SBS) 大鼠模型中肠道运动的机制。大鼠分为三组:Sham大鼠进行肠横断;SBS-NSI 大鼠接受了 75% 的肠切除术,并在处死时呈现正常的肠道大小 (NSI) 和过度运动模式;SBS-DYS 显示肠运动障碍 (DYS) 扩大肠和抑制运动模式。2周后处死动物。Illumina 的数字基因表达 (DGE) 分析用于确定黏膜样本中与肠道运动相关的基因表达谱。使用实时 PCR、蛋白质印迹和免疫组织化学测定 Cajal (ICC) 基因的肠动力相关和间质细胞和肠肌肉层中的蛋白质表达。通过微型计算机断层扫描研究胃肠道运动。从十钙在 SBS 与 Sham 动物中,2 +信号通路相关基因、空肠中的 6 个基因和回肠中的 7 个基因被下调。通过实时 PCR 确认 TMEM16A mRNA 和蛋白质的下调。SBS-NSI 大鼠的快速肠道转运时间与 TMEM 16A、c-kit 和波形蛋白 mRNA 和蛋白质表达的轻度下降相关(与 Sham 动物相比)。与其他两组相比,SBS-DYS 大鼠表现出肠循环扩大和小肠排空延迟(影像学研究),这与 TMEM 16A、c-kit、波形蛋白、生长素释放肽 mRNA 和蛋白质水平的显着下调相关。总之,大鼠大肠切除术后两周,肠道运动受损与波形蛋白和生长素释放肽基因和蛋白质水平降低以及 ICC(c-kit 和 TMEM16A)损失有关。
更新日期:2020-12-16
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