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溃疡性结肠炎和感染性腹泻患者中瘦素和促炎细胞因子的表达和释放。

Expression and release of leptin and proinflammatory cytokines in patients with ulcerative colitis and infectious diarrhea.

机构信息

Gastroenterology, Hepatology and Infectious Diseases Clinic, Jagiellonian University Medical College, Cracow, Poland.

出版信息

J Physiol Pharmacol. 2012 Oct;63(5):471-81.

Abstract

Leptin plays not only an important role in regulation of food intake, but also in the mechanism of inflammation. The universal presence of leptin in the cells of immune system and its secretion by these cells caused increasing interest in the role of this hormone in ulcerative colitis (UC). We determined the role of leptin in 80 patients, aged from 18 to 69 years, including 50 patients with active UC and 30 patients with infectious diarrhea. The tests were performed within 48 hours of the first symptoms, in the period of remission of UC and 8 weeks after resolution of infectious diarrhea. Endoscopy was performed in each patient, and the biopsy samples were taken for the assessments of expression of mRNA for leptin, IL-1β, IL-6 and TNF-α by RT-PCR and Western blot. Blood tests included concentrations of leptin, IL-1β, IL-6 and TNF-α. In addition, the plasma levels of leptin, IL-1β, IL-6 and TNF-α were assessed by ELISA. Serum concentrations of leptin was significantly increased in patients with exacerbation of UC over that in patients with UC in remission. The serum leptin concentration was significantly higher in patients with infectious diarrhea, than the patients that recovered from infectious diarrhea. The leptin protein was overexpressed in the biopsy samples of the mucosa of large intestine compared to those with exacerbation of UC, and in patients after successful recovery from infectious diarrhea. The leptin mRNA was overexpressed in patients with infectious diarrhea compared with that in the group of patients after successful recovery from this condition. Serum concentrations of leptin failed to correlate with severity of exacerbation of UC and with extent of intestinal inflammatory lesions in patients with UC. However, the correlation was observed between serum concentrations of leptin in patients with exacerbation of UC and serum concentrations of proinflammatory cytokines IL-1β and TNF-α. We conclude that 1) the increased leptin in exacerbated UC is related to the increased serum proinflammatory cytokines IL-1β, TNF-α and IL-6 levels; 2) In patients with infectious diarrhea, the concentrations of leptin in intestinal mucosa correlates with serum concentrations of cytokines IL-1β, IL-6 and TNF-α and with an increased expression of leptin mRNA in intestinal mucosa but not with alterations in serum levels of this hormone; 3) leptin may serve as useful predictive marker of inflammation in inflammatory bowel disease (IBD).

摘要

瘦素不仅在调节食物摄入方面起着重要作用,而且在炎症机制中也起着重要作用。瘦素普遍存在于免疫系统的细胞中,并由这些细胞分泌,这引起了人们对这种激素在溃疡性结肠炎(UC)中的作用的越来越多的兴趣。我们在 80 名年龄在 18 至 69 岁之间的患者中确定了瘦素的作用,其中包括 50 名活动期 UC 患者和 30 名感染性腹泻患者。在出现第一个症状后的 48 小时内进行了测试,在 UC 缓解期间和感染性腹泻缓解后 8 周进行了测试。对每位患者进行了内镜检查,并采集活检样本,通过 RT-PCR 和 Western blot 评估瘦素、IL-1β、IL-6 和 TNF-α的 mRNA 表达。血液测试包括瘦素、IL-1β、IL-6 和 TNF-α的浓度。此外,还通过 ELISA 评估了血浆中瘦素、IL-1β、IL-6 和 TNF-α的水平。UC 加重患者的血清瘦素浓度明显高于 UC 缓解患者。感染性腹泻患者的血清瘦素浓度明显高于感染性腹泻恢复患者。与 UC 加重患者相比,大肠黏膜活检样本中的瘦素蛋白表达增加,与感染性腹泻成功恢复的患者相比也是如此。与成功恢复感染性腹泻的患者相比,感染性腹泻患者的瘦素 mRNA 表达增加。UC 加重患者的血清瘦素浓度与 UC 患者的炎症病变严重程度和肠道炎症病变范围无关。然而,在 UC 加重患者中,血清瘦素浓度与促炎细胞因子 IL-1β和 TNF-α的血清浓度之间存在相关性。我们得出的结论是:1)UC 加重患者中增加的瘦素与血清促炎细胞因子 IL-1β、TNF-α和 IL-6 水平的增加有关;2)感染性腹泻患者,肠黏膜中的瘦素浓度与血清细胞因子 IL-1β、IL-6 和 TNF-α浓度以及肠黏膜中瘦素 mRNA 的表达增加相关,但与激素血清水平的变化无关;3)瘦素可能是炎症性肠病(IBD)炎症的有用预测标志物。

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