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1,25-二羟基维生素D3对盐酸/乙醇诱导的大鼠胃损伤的影响。

The effect of 1,25 dihydroxyvitamin D3 on HCl/Ethanol-induced gastric injury in rats.

作者信息

Sahin Hasan Huseyin, Cumbul Alev, Uslu Unal, Yilmaz Zeynep, Ercan Feriha, Alican Inci

机构信息

Marmara University School of Medicine, Department of Physiology, 34854 Maltepe, Istanbul, Turkey.

Yeditepe University School of Medicine, Department of Histology and Embryology, 34755 Atasehir, Istanbul, Turkey.

出版信息

Tissue Cell. 2018 Apr;51:68-76. doi: 10.1016/j.tice.2018.03.003. Epub 2018 Mar 4.

Abstract

This study evaluated ulceroprotective and antioxidant effect of 1,25 dihydroxyvitamin D3 against gastric damage in rats. Rats were treated intraperitoneally with either 1,25 dihydroxyvitamin D3 (0.25 μg/kg) or saline for 14 days. On day-15, the non-selective cyclooxygenase inhibitor indomethacin (10 mg/kg; subcutaneously), the inhibitor of sulfhydryl groups N-ethylmaleimide (10 mg/kg; intraperitoneally) or ATP-sensitive K+ channel blocker glibenclamide (10 mg/kg; orally) was given prior to 1,25 dihydroxyvitamin D3. Animals were euthanized at 60 min post ulcerogenic challenge (0.3 M HCl and 60% ethanol (0.2 mL; orally). Stomach and blood were collected for biochemical and histological evaluations. HCl/Ethanol group revealed severely damaged mucous and glandular epithelium with diffuse hemorrhage and inflammatory cell infiltration (microscopic score: 10.67 ± 0.67 and ulcer index: 33.13 ± 5.09). 1,25 dihydroxyvitamin D3 decreased the extent of damage (microscopic score: 6.80 ± 0.02 and ulcer index: 19.00 ± 4.34; p < 0.05), and the elevations in gastric malondialdehyde level (p < 0.001), myeloperoxidase activity (p < 0.001), nuclear factor-κB expression (p < 0.05), and apoptotic index (p < 0.05) following HCl/Ethanol challenge. Decreased gastric glutathione following HCl/Ethanol administration was restored by 1,25 dihydroxyvitamin D3 (p < 0.01). These findings demonstrated protection of the gastric mucosa against HCl/Ethanol-induced injury by 1,25 dihydroxyvitamin D3 via attenuation of inflammatory reaction, oxidative stress and apoptosis.

摘要

本研究评估了1,25-二羟基维生素D3对大鼠胃损伤的溃疡保护作用和抗氧化作用。大鼠腹腔注射1,25-二羟基维生素D3(0.25μg/kg)或生理盐水,持续14天。在第15天,在给予1,25-二羟基维生素D3之前,皮下注射非选择性环氧化酶抑制剂吲哚美辛(10mg/kg)、腹腔注射巯基抑制剂N-乙基马来酰亚胺(10mg/kg)或口服ATP敏感性钾通道阻滞剂格列本脲(10mg/kg)。在致溃疡刺激(0.3M盐酸和60%乙醇(0.2mL;口服))后60分钟对动物实施安乐死。收集胃和血液进行生化和组织学评估。盐酸/乙醇组显示黏膜和腺上皮严重受损,伴有弥漫性出血和炎性细胞浸润(显微镜评分为10.67±0.67,溃疡指数为33.13±5.09)。1,25-二羟基维生素D3减轻了损伤程度(显微镜评分为6.80±0.02,溃疡指数为19.00±4.34;p<0.05),并降低了盐酸/乙醇刺激后胃丙二醛水平升高(p<0.001)、髓过氧化物酶活性升高(p<0.001)、核因子-κB表达升高(p<0.05)以及凋亡指数升高(p<0.05)。1,25-二羟基维生素D3恢复了盐酸/乙醇给药后降低的胃谷胱甘肽水平(p<0.01)。这些发现表明,1,25-二羟基维生素D3通过减轻炎症反应、氧化应激和细胞凋亡,对胃黏膜起到保护作用,使其免受盐酸/乙醇诱导的损伤。

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