Adiponectin receptor agonist AdipoRon relieves endotoxin-induced acute hepatitis in mice  

作　　者：Wen-Ze Xiao Li Zhang 

机构地区：[1]Department of Rheumatology,Shanghai Pudong Hospital,Fudan University Pudong Medical Center,Shanghai 201399,China [2]Department of Pathophysiology,Chongqing Medical University,Chongqing 400016,China

出　　处：《Chinese Medical Journal》2019年第20期2438-2445,共8页中华医学杂志（英文版）

摘　　要：Background:Adiponectin is the most abundant adipokines that plays critical roles in the maintenance of energy homeostasis as well as inflammation regulation. The half-life of adiponectin is very short and the small-molecule adiponectin receptor agonist has been synthesized recently. In the present study, the potential roles of AdipoRon, an adiponectin receptor agonist, in a mouse model of lipopolysaccharide (LPS)/D-galactosamine (D-Gal)-induced acute hepatitis was explored.Methods:BALB/c mice (n = 144, male) were divided into three sets. In set 1, 32 mice were randomized into four groups: the control group, the AdipoRon group, the LPS/D-Gal group, and the AdipoRon + LPS/D-Gal group. The mice in set 1 were sacrificed after LPS/D-Gal treatment, and the plasma samples were collected for detection of tumor necrosis factor-alpha (TNF-α). In set 2, the 32 mice were also divided into four groups similar to that of set 1. The mice were sacrificed 6 h after LPS/D-Gal injection and plasma samples and liver were collected. In set 3, 80 mice (divided into four groups, n = 20) were used for survival observation. The survival rate, plasma aminotransferases, histopathological damage were measured and compared between these four groups.Results:AdipoRon suppressed the elevation of plasma aminotransferases (from 2106.3 ± 781.9 to 286.8 ± 133.1 U/L for alanine aminotransferase, P < 0.01;from 566.5 ± 243.4 to 180.1 ± 153.3 U/L for aspartate aminotransferase, P < 0.01), attenuated histopathological damage and improved the survival rate (from 10% to 60%) in mice with LPS/D-Gal-induced acute hepatitis. Additionally, AdipoRon down-regulated the production of TNF-α (from 328.6 ± 121.2 to 213.4 ± 52.2 pg/mL, P < 0.01), inhibited the activation of caspase-3 (from 2.04-fold to 1.34-fold of the control), caspase-8 (from 2.03-fold to 1.31-fold of the control), and caspase-9 (from 2.14-fold to 1.43-fold of the control), and decreased the level of cleaved caspase-3 (0.28-fold to that of the LPS/D-Gal group). The number of terminal deoxy

关 键 词：AdipoRon LIPOPOLYSACCHARIDE D-GALACTOSAMINE ACUTE HEPATITIS Apoptosis 

分 类 号：R28[医药卫生—中药学]