LXRα/SREBP-1c在砷致大鼠脂代谢紊乱中的作用  

Role of LXRα/SREBP-1c in arsenic induced lipid metabolism disorders in rats

作　　者：王登杰 王文娟[1] 邹忠兰 张爱华[1] Wang Dengjie;Wang Wenjuan;Zou Zhonglan;Zhang Aihua(Key Laboratory for Environmental Pollution Monitor and Disease Control,Ministry of Education,Department of Toxicology,School of Public Health,Guizhou Medical University,Guiyang 550025,China)

机构地区：[1]贵州医科大学环境污染与疾病监控教育部重点实验室公共卫生与健康学院毒理学系,贵阳550025

出　　处：《中华地方病学杂志》2022年第7期517-523,共7页Chinese Journal of Endemiology

基　　金：国家自然科学基金(81872569、81903267、U1812403)。

摘　　要：目的:探讨肝X受体α(LXRα)/固醇调节元件结合蛋白1c(SREBP-1c)在砷致大鼠脂代谢紊乱中的作用,为砷致脂代谢紊乱的机制研究提供依据。方法:将24只健康清洁级Wistar大鼠,按体质量(80~100 g)采用随机数字表法分为4组,每组6只,雌雄各半。对照组给予去离子水灌胃;低、中、高砷剂量组分别给予2.5、5.0、10.0 mg·kg-1·d-1亚砷酸钠水溶液灌胃,每周染砷6 d,连续处理4个月,实验终期采集各组大鼠血液及肝脏样本。采用电感耦合等离子体质谱仪(ICP-MS)检测大鼠肝组织砷含量;全自动生化分析仪检测大鼠血清甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)水平;实时荧光定量PCR法检测肝组织LXRα、SREBP-1c mRNA表达水平;蛋白免疫印迹法(Western blot)检测肝组织LXRα、SREBP-1c、乙酰辅酶A羧化酶(ACC)、磷酸化ACC(pACC)蛋白表达水平。结果:低、中、高砷剂量组大鼠肝砷含量分别为(61.04±4.98)、(62.66±6.71)、(87.86±13.89)μg/g,均高于对照组[(2.43±0.63)μg/g,P均<0.05],且高砷剂量组大鼠肝砷含量高于低、中砷剂量组(P均<0.05)。低、中、高砷剂量组大鼠血清TG水平分别为(0.90±0.17)、(1.28±0.24)、(1.82±0.18)mmol/L,均高于对照组[(0.50±0.12)mmol/L,P均<0.05];低、中、高砷剂量组大鼠血清LDL-C水平分别为(0.54±0.04)、(0.63±0.07)、(0.69±0.08)mmol/L,均高于对照组[(0.27±0.05)mmol/L,P均<0.05];中、高砷剂量组大鼠血清TC水平分别为(1.88±0.23)、(2.10±0.10)mmol/L,均高于对照组[(1.51±0.14)mmol/L,P均<0.05];中、高砷剂量组大鼠血清HDL-C水平分别为(0.84±0.11)、(0.71±0.14)mmol/L,均低于对照组[(1.15±0.08)mmol/L,P均<0.05];且中、高砷剂量组大鼠血清TG、LDL-C水平均高于低砷剂量组(P均<0.05),高砷剂量组大鼠血清TG水平高于中砷剂量组(P<0.05)。高砷剂量组大鼠肝组织LXRαmRNA表达水平高于对照组及低砷剂量组(P均<0.05);低、中、�Objective To investigate the role of liver X-activated receptor(LXRα)/sterol-regulatory element binding protein(SREBP-1c)in arsenic induced lipid metabolism disorders in rats,and to provide a basis for study the mechanism of arsenic induced lipid metabolism disorders.Methods Twenty-four healthy clean grade Wistar rats,were randomly divided into 4 groups according to body weight(80-100 g)by the random number table method,with 6 rats in each group,half male and half female.Rats in control group were given deionized water by gavage.The low,medium and high arsenic dose groups were given 2.5,5.0 and 10.0 mg·kg-1·d-1 sodium arsenite solution by gavage,respectively.They were exposed to arsenic for 6 days a week for 4 months.At the end of the experiment,blood and liver samples of rats in each group were collected.The hepatic arsenic content was determined by inductively coupled plasma mass spectrometry(ICP-MS);the serum levels of triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)were measured by automatic biochemical analyzer.The mRNA expression levels of LXRαand SREBP-1c in liver tissues were determined by real-time PCR;the protein expression levels of LXRα,SREBP-1c,acetyl CoA carboxylase(ACC)and phospho-ACC(pACC)in liver tissues were determined by Western blotting.Results The hepatic arsenic contents of rats in low,medium and high arsenic dose groups were(61.04±4.98),(62.66±6.71)and(87.86±13.89)μg/g,respectively,which were higher than that in control group[(2.43±0.63)μg/g,P<0.05],and the hepatic arsenic content of rats in high arsenic dose group was higher than those in low and medium arsenic dose groups(P<0.05).The serum TG levels of rats in low,medium and high arsenic dose groups were(0.90±0.17),(1.28±0.24)and(1.82±0.18)mmol/L,respectively,which were higher than that in control group[(0.50±0.12)mmol/L,P<0.05];the serum LDL-C levels of rats in low,medium and high arsenic dose groups were(0.54±0.04),(0.63±0.07)and(0.69±0.08)

关 键 词：大鼠 砷 肝脏 脂代谢 

分 类 号：R994[医药卫生—毒理学]