Wang Cuifen, Wu Miaozong, Arvapalli Ravikumar, Dai Xiaoniu, Mahmood Muhammad, Driscoll Henry, Rice Kevin M, Blough Eric
Center for Diagnostic Nanosystems, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA.
Cell Physiol Biochem. 2014;33(4):1139-48. doi: 10.1159/000358683. Epub 2014 Apr 11.
BACKGROUND/AIMS: Obesity is an independent risk factor for the development of kidney disease. The purpose of this study was to determine how obesity may contribute to renal damage and whether acetaminophen ingestion can diminish obesity-associated renal cell injury in the obese Zucker rat model.
Male obese Zucker rats (4 weeks old, n=6) were treated with acetaminophen (30 mg / kg body weight / day) for 26 weeks. Age matched obese control (OC), obese vehicle (OV, 0.073 mL DMSO/kg/d), and lean Zucker rats (LC) were used to determine the effects of treatment and obesity.
Compared to lean control rats, renal lipid deposition, expression of the endoplasmic reticulum (ER) stress protein GRP78 and activation of the ER stress-related eIF2α-ATF4-CHOP, caspase 12, and JNK-MAPK signaling pathways were increased in the obese control and obese vehicle rats. These alterations were associated with the elevated renal cell apoptosis and urinary albumin excretion. Acetaminophen treatment decreased renal lipid deposition, ER-stress related signaling, apoptosis and albuminuria.
These data suggest that the protective effects of low dose acetaminophen on renal injury are mediated, at least in part, through attenuation of ER stress.
背景/目的：肥胖是肾病发生的独立危险因素。本研究旨在确定肥胖如何导致肾损伤，以及对乙酰氨基酚的摄入是否能减轻肥胖 Zucker 大鼠模型中与肥胖相关的肾细胞损伤。
雄性肥胖 Zucker 大鼠（4 周龄，n = 6）接受对乙酰氨基酚（30 mg / kg 体重 / 天）治疗 26 周。采用年龄匹配的肥胖对照（OC）、肥胖溶媒对照（OV，0.073 mL 二甲基亚砜 / kg / d）和瘦 Zucker 大鼠（LC）来确定治疗和肥胖的影响。
与瘦对照大鼠相比，肥胖对照和肥胖溶媒对照大鼠的肾脂质沉积、内质网（ER）应激蛋白 GRP78 的表达以及 ER 应激相关的 eIF2α - ATF4 - CHOP、半胱天冬酶 12 和 JNK - MAPK 信号通路的激活均增加。这些改变与肾细胞凋亡增加和尿白蛋白排泄增加有关。对乙酰氨基酚治疗可减少肾脂质沉积、ER 应激相关信号传导、细胞凋亡和蛋白尿。
这些数据表明，低剂量对乙酰氨基酚对肾损伤的保护作用至少部分是通过减轻 ER 应激介导的。
