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、高砷剂量组和对照组大鼠肝组织SREBP-1c mRNA表达水平比较,差异无统计学意义(P>0.05)。中、高砷剂量组大鼠肝组织LXRα蛋白表达水平均高于对照组(P均<0.05);高砷剂量组大鼠肝组织LXRα蛋白表达水平高于低砷剂量组(P<0.05);高砷剂量组大鼠肝组织SREBP-1c、ACC蛋白表达水平均高于对照组(P均<0.05)。染砷大鼠血清TG、TC、LDL-C水平,肝组织LXRαmRNA及LXRα、SREBP-1c、ACC蛋白表达水平与肝砷含量均呈正相关(r=0.84、0.62、0.89、0.55、0.54、0.64、0.70,P均<0.05),血清HDL-C水平与肝砷含量呈负相关(r=-0.75,P<0.001)。结论:亚砷酸钠可引起大鼠血清TG、TC、LDL-C水平升高、HDL-C水平降低以及肝脏LXRα、SREBP-1c蛋白表达水平升高,提示砷致大鼠脂代谢紊乱可能与其上游LXRα/SREBP-1c调控机制有关。
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)mmol/L,respectively,which were higher than that in control group[(0.27±0.05)mmol/L,P<0.05];the serum TC levels of rats in medium and high arsenic dose groups were(1.88±0.23)and(2.10±0.10)mmol/L,respectively,which were higher than that in control group[(1.51±0.14)mmol/L,P<0.05];the serum HDL-C levels of rats in medium and high arsenic dose groups were(0.84±0.11)and(0.71±0.14)mmol/L,respectively,which were lower than that in control group[(1.15±0.08)mmol/L,P<0.05];and the serum levels of TG and LDL-C in medium and high arsenic dose groups were higher than those in low arsenic dose group(P<0.05),and the serum level of TG in high arsenic dose group was higher than that in medium arsenic dose group(P<0.05).The mRNA expression level of hepatic LXRαof rats in high arsenic dose group was higher than those in control group and low arsenic dose group(P<0.05);there was no significant difference in mRNA expression levels of hepatic SREBP-1c of rats between low,medium and high arsenic dose groups and control group(P>0.05).The protein expression levels of hepatic LXRαof rats in medium and high arsenic dose groups were higher than that in control group(P<0.05),and high arsenic dose group was higher than low arsenic dose group(P<0.05);the protein expression levels of hepatic SREBP-1c and ACC of rats in high arsenic dose group were higher than that in control group(P<0.05).There was a positive correlation between hepatic arsenic content in arsenic-exposed rats and the serum levels of TG,TC,LDL-C,the mRNA expression level of hepatic LXRα,the protein expression levels of hepatic LXRα,SREBP-1c and ACC(r=0.84,0.62,0.89,0.55,0.54,0.64,0.70,P<0.05),and the serum level of HDL-C was negatively correlated with the hepatic arsenic content in arsenic-exposed rats(r=-0.75,P<0.001).Conclusion Sodium arsenite can increase the serum levels of TG,TC and LDL-C,decrease the serum level of HDL-C and increase the protein expression levels of LXRαand SREBP-1c in liver tissues,suggesting that arsenic induced lipid metabolism disorders in rats may be related to the upstream regulation mechanism of LXRα/SREBP-1c.
作者
王登杰
王文娟
邹忠兰
张爱华
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)
出处
《中华地方病学杂志》
CAS
北大核心
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)。
关键词
大鼠
砷
肝脏
脂代谢
Rats
Arsenic
Liver
Lipid metabolism
