邻苯二甲酸二(2-乙基己基)酯对大鼠脂代谢的影响及可能机制  

Effects of di(2-ethylhexyl)phthalate on lipid metabolism in rats and potential mechanism

作　　者：朱粤 雷瑞琛 周泓洋 胡雨婷 李丽萍[1] 李玲[1] 刘贺荣[1] 德小明[1] ZHU Yue;LEI Ruichen;ZHOU Hongyang;HU Yuting;LI Liping;LI Ling;LIU Herong;DE Xiaoming(School of Public Health/Ningxia Key Laboratory of Environmental Factors and Control of Chronic Diseases,Ningxia Medical University,Yinchuan,Ningxia 750004,China)

机构地区：[1]宁夏医科大学公共卫生学院/宁夏环境因素与慢性病控制重点实验室,宁夏银川750004

出　　处：《环境与职业医学》2024年第10期1167-1172,1185,共7页Journal of Environmental and Occupational Medicine

基　　金：宁夏大学生科技创新项目(S202210752005)。

摘　　要：[背景]邻苯二甲酸二(2-乙基己基)酯(DEHP)是目前用量最大、应用最广泛的邻苯二甲酸酯类化合物,其对脂代谢的影响受到众多学者的关注,然而其机制尚不清楚。[目的]观察DEHP对大鼠脂代谢的影响及可能的机制,为DEHP对人群脂代谢的影响提供研究基础和依据。[方法]40只初断乳的健康雄性SD大鼠,随机分成4组:溶剂对照组(0 mg·kg^(−1)DEHP)、DEHP低剂量组(187 mg·kg^(−1))、DEHP中剂量组(375 mg·kg^(−1))、DEHP高剂量组(750 mg·kg^(−1))。采用经口灌胃的方式染毒,每周染毒6 d,连续8周。染毒期间每周称量大鼠体重一次,于末次染毒结束后24 h,20%乌拉坦麻醉,心尖穿刺取血处死大鼠。取大鼠肝脏称重,用于苏木精-伊红(HE)病理组织学观察。用逆转录聚合酶链反应(RT-PCR)检测肝脏组织脂代谢相关基因Janus激酶3(JAK3)、信号转导与转录激活因子5b(STAT5b)、过氧化物酶体增殖物激活受体γ(PPARγ)mRNA水平,Western blot法检测肝脏中脂代谢相关蛋白JAK3、STAT5b、PPARγ的表达水平。[结果]与对照组比较,各实验组大鼠体重增长量差异均无统计学意义(P>0.05)。染毒组大鼠的肝脏脏器系数皆高于对照组(P<0.001),且随DEHP染毒剂量增高而升高。DEHP低、中、高剂量染毒组血清中高密度脂蛋白胆固醇(HDL-C)降低(P<0.001),DEHP高剂量染毒组血清中低密度脂蛋白胆固醇(LDL-C)升高(P<0.05)。肝脏病理形态学结果显示,各DEHP染毒组大鼠肝细胞出现不同程度增大、水肿,间质疏松,细胞排列不整齐,表现为大鼠肝脏组织炎性细胞浸润和肝细胞脂肪变性样改变。肝脏脂代谢相关基因mRNA水平检测结果显示,各DEHP染毒组大鼠肝脏组织JAK3、STAT5b、PPARγmRNA水平与对照组相比均降低(P<0.001)。肝脏脂代谢相关蛋白水平检测结果显示,与对照组相比,DEHP低、中、高剂量组JAK3蛋白相对表达水平均降低(P<0.05),DEHP中、高剂量组STAT5b、PPARγ蛋白相[Background]Di(2-ethylhexyl)phthalate(DEHP)is the highest consumed and the most widely used phthalic acid ester,their effects on lipid metabolism have attracted the attention of many scholars.However,the associated mechanism is still unclear.[Objective]To observe the effect of DEHP on lipid metabolism in rats,probe its possible mechanism,and provide a research basis for the effect of DEHP on human lipid metabolism.[Methods]Forty healthy male SD rats were randomly divided into 4 groups:solvent control(0 mg·kg^(−1)DEHP),low DEHP(187 mg·kg^(−1)),medium DEHP(375 mg·kg^(−1)),and high DEHP(750 mg·kg^(−1))groups.DEHP was administered by oral gavage for 6 d per week,consecutively 8 weeks.The rats were weighed once a week during the exposure period.At 24 h after the last exposure,the rats were anesthetized with 20%urethane and sacrificed by apical puncture.Rat livers were harvested and weighed before hematoxylin-eosin(HE)histopathological observation.Reverse transcription-polymerase chain reaction(RT-PCR)was used to detect the mRNA levels of lipid metabolism-related genes Janus kinase 3(JAK3),signal transducer and activator of transcription 5b(STAT5b),and peroxisome proliferator-activated receptorγ(PPARγ)in liver,and Western blot was used to detect the expression levels of lipid metabolism-related proteins JAK3,STAT5b,and PPARγin liver.[Results]Compared with the control group,there was no significant difference in the body weight gain of the rats in each group(P>0.05).The liver organ coefficients of the DEHP exposure groups were higher than that of the control group(P<0.001),and increased with higher DEHP dosages.The level of high-density lipoprotein cholesterol(HDL-C)in serum decreased in all DEHP exposure groups(P<0.05),and the level of low-density lipoprotein cholesterol(LDL-C)in serum increased in the high DEHP group(P<0.05).The results of liver histopathological morphology showed that the hepatocytes of each DEHP group were enlarged and edematous in varying degrees,with loose stroma and irregular arran

关 键 词：邻苯二甲酸二(2-乙基己基)酯 脂代谢 Janus激酶3 信号转导与转录激活因子5b 过氧化物酶体增殖物激活受体Γ 信号通路 

分 类 号：R11[医药卫生—公共卫生与预防医学]