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1,25-二羟基维生素D3通过调节辅助性T细胞(Th)1和Th17的激活来调控慢性结肠炎的发展。

1,25-dihydroxyvitamin D3 regulates the development of chronic colitis by modulating both T helper (Th)1 and Th17 activation.

作者信息

Zhang Hong, Wu Hui, Liu Lei, Li Hui, Shih David Q, Zhang Xiaolan

机构信息

Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang, China.

The Second Department of Gastroenterology, The Fifth People's Hospital of DaTong, DaTong, China.

出版信息

APMIS. 2015 Jun;123(6):490-501. doi: 10.1111/apm.12378. Epub 2015 Apr 23.

Abstract

T helper (Th)1 and Th17 cells play a critical role in inflammatory bowel disease (IBD). 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ) has emerged as a direct regulator of immune system function. Mice were grouped as follows: Control group (received PBS, n = 10), DSS group (received 2% DSS and PBS, n = 10), and DSS+VD group (received 2% DSS and 1,25(OH)2 D3 , n = 10). The disease activity index (DAI), colon length, and damage store of the mice were observed; the spleen length, weight, spleen index, and mononuclear cells of spleen were measured; mononuclear cells from mesenteric lymph nodes (MLN) were measured, and the levels of Th 1 and Th17 cytokines in the colon mucosa and spleen were measured. Mice in the DSS group developed severe diarrhea, rectal bleeding, and marked BW loss. Histological examination revealed extensive ulceration and inflammatory cell infiltration in the colon, and the structure of the spleen was disordered, infiltrated with inflammatory cytokines in red pulp. In the DSS group, mononuclear cell numbers from MLN and spleen were increased, and enhanced proteins and mRNA levels of Th 1 and Th17 cytokines were detected. In the DSS+VD group, 1,25(OH)2 D3 ameliorated the inflammation of the colon and spleen. In addition, 1,25(OH)2 D3 down-regulated the levels of Th 1 and Th17 cytokines. 1,25(OH)2 D3 represents a novel therapeutic drug for UC, which may correlate to inhibit the activation of Th1 and Th17 cells.

摘要

辅助性T细胞(Th)1和Th17细胞在炎症性肠病(IBD)中起关键作用。1,25-二羟基维生素D3(1,25(OH)2 D3)已成为免疫系统功能的直接调节因子。将小鼠分组如下:对照组(接受磷酸盐缓冲液,n = 10)、葡聚糖硫酸钠(DSS)组(接受2% DSS和磷酸盐缓冲液,n = 10)以及DSS + 维生素D(VD)组(接受2% DSS和1,25(OH)2 D3,n = 10)。观察小鼠的疾病活动指数(DAI)、结肠长度和损伤评分;测量脾脏长度、重量、脾脏指数以及脾脏单核细胞;测量肠系膜淋巴结(MLN)的单核细胞,并检测结肠黏膜和脾脏中Th1和Th17细胞因子的水平。DSS组小鼠出现严重腹泻、直肠出血和明显的体重减轻。组织学检查显示结肠广泛溃疡和炎性细胞浸润,脾脏结构紊乱,红髓中有炎性细胞因子浸润。在DSS组中,MLN和脾脏的单核细胞数量增加,并且检测到Th1和Th17细胞因子的蛋白质和mRNA水平升高。在DSS + VD组中,1,25(OH)2 D3改善了结肠和脾脏的炎症。此外,1,25(OH)2 D3下调了Th1和Th17细胞因子的水平。1,25(OH)2 D3是一种用于治疗溃疡性结肠炎(UC)的新型治疗药物,这可能与抑制Th1和Th17细胞的活化有关。

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