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热量限制模拟物2-脱氧葡萄糖减轻了脂多糖/D-半乳糖胺诱导的小鼠致死性肝损伤。

Caloric restriction mimetic 2-deoxyglucose alleviated lethal liver injury induced by lipopolysaccharide/D-galactosamine in mice.

作者信息

Che Qian, Lin Ling, Ai Qing, Ge Pu, Dai Jie, Jiang Rong, Zhou Dan, Wan Jingyuan, Zhang Li

机构信息

Department of Pathophysiology, Chongqing Medical University, Chongqing, China.

Department of Physiology, Chongqing Medical University, Chongqing, China.

出版信息

Biochem Biophys Res Commun. 2015 Apr 10;459(3):541-6. doi: 10.1016/j.bbrc.2015.02.145. Epub 2015 Mar 5.

DOI:10.1016/j.bbrc.2015.02.145
PMID:25749337
Abstract

The glycolytic inhibitor 2-deoxyglucose (2-DG) is a calorie restriction (CR) mimetic produces CR-like beneficial effects in both acute and chronic pathological processes, but whether 2-DG is also helpful in critical and life-threatening situation is not known. In the present study, the potential benefits of 2-DG in lipopolysaccharide/D-galactosamine (LPS/D-Gal)-induced lethal liver injury were investigated. The results indicated that treatment with 2-DG suppressed the elevation of plasma aminotransferases, alleviated the histopathological abnormalities and improved the survival rate of LPS/D-Gal-exposed mice. Treatment with 2-DG also suppressed the production of pro-apoptotic cytokine TNF-α, the phosphorylation of JNK, the activation of caspase cascade and the count of TUNEL-positive apoptotic hepatocytes. These data suggested that the CR mimetic 2-DG could also provide beneficial effects in lethal pathological process such as LPS/D-Gal-induced fulminant liver injury.

摘要

糖酵解抑制剂2-脱氧葡萄糖(2-DG)是一种模拟热量限制(CR)的物质,在急性和慢性病理过程中均能产生类似CR的有益作用,但2-DG在危急和危及生命的情况下是否也有帮助尚不清楚。在本研究中,研究了2-DG在脂多糖/D-半乳糖胺(LPS/D-Gal)诱导的致死性肝损伤中的潜在益处。结果表明,用2-DG治疗可抑制血浆转氨酶升高,减轻组织病理学异常,并提高LPS/D-Gal暴露小鼠的存活率。用2-DG治疗还可抑制促凋亡细胞因子TNF-α的产生、JNK的磷酸化、半胱天冬酶级联反应的激活以及TUNEL阳性凋亡肝细胞的计数。这些数据表明,模拟CR的2-DG在致死性病理过程如LPS/D-Gal诱导的暴发性肝损伤中也能提供有益作用。

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