研究报告

  • 李丹阳,宋鹏琰,张妍,张林超,钟秀会,刘连涛,王晓丹.妊娠期染毒全氟辛酸对子代雌鼠肝脏损伤及PPAR-α通路的影响[J].环境科学学报,2018,38(11):4520-4526

  • 妊娠期染毒全氟辛酸对子代雌鼠肝脏损伤及PPAR-α通路的影响
  • Effect of pregnancy exposure to perfluorooctanoic acid (PFOA) on liver injury and ppar-α pathway of female offspring mice
  • 基金项目:国家自然科学基金(No.31502111);河北省自然科学基金(No.C2016204097)
  • 作者
  • 单位
  • 李丹阳
  • 河北农业大学中兽医学院, 保定 071000
  • 宋鹏琰
  • 河北农业大学中兽医学院, 保定 071000
  • 张妍
  • 河北农业大学中兽医学院, 保定 071000
  • 张林超
  • 河北农业大学中兽医学院, 保定 071000
  • 钟秀会
  • 河北农业大学中兽医学院, 保定 071000
  • 刘连涛
  • 河北农业大学中兽医学院, 保定 071000
  • 王晓丹
  • 河北农业大学中兽医学院, 保定 071000
  • 摘要:为了探讨妊娠期染毒全氟辛酸(Perfluorooctanoicacid,PFOA)对子代雌鼠肝脏的损伤作用,以及对过氧化物酶体增殖物激活受体α(PPARα)及其调控的下游脂肪酸氧化基因表达量的影响.本研究将50只孕0 d的小鼠随机分为5组,每组10只.孕1~17 d,对照组小鼠每天灌服0.2 mL去离子水,其余4组每天小鼠分别灌服0.2 mL不同剂量(1.0、2.5、5.0、10.0 mg·kg-1)的PFOA,仔鼠生长到21日龄剖杀,分离血清并采集肝脏.同时,计算母鼠的流产率、子代存活率、肝脏指数,采用HE染色观察肝脏病理变化.最后,检测血清中天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)的活性,用ELISA方法检测肝脏中超氧化物歧化酶(SOD)和过氧化氢酶(CAT)的含量,用qPCR法检测PPARα及其调控的下游脂肪酸氧化基因的表达量.结果显示,与对照组相比,10 mg·kg-1 PFOA处理可显著升高母鼠的流产率(p<0.05),降低仔鼠成活率(p<0.01),极显著增加子代肝脏指数(p<0.01),导致肝细胞肿大,发生空泡变性.PFOA处理组中AST和ALT的活性及SOD和CAT的含量极显著上调(p<0.01),PPAR-α基因的表达量极显著下降(p<0.01),其调控的有关脂肪酸氧化基因极显著上升(p<0.01).研究表明,妊娠期染毒PFOA可增加母鼠流产率和仔鼠死亡率,增加仔鼠肝脏指数,造成肝细胞肿大和坏死.并且通过激活子代雌鼠PPAR-α通路,加剧脂肪酸氧化,使活性氧沉积,造成氧化应激,导致肝脏损伤.
  • Abstract:To investigate the effect of pregnancy exposure to perfluorooctanoic acid (PFOA) on the hepatotoxicity of female offspring mice and gene expression levels of peroxisome proliferator-activated receptor -α (PPAR-α) and downstream fatty acid oxidation be regulated by it. Fifty pregnant Kunming mice were randomly divided into 5 groups with 10 of each,which were treated with 0.2 mL PFOA solution dissolved with deionized water at 0,1.0,2.5,5.0 and 10.0 mg·kg-1 BW,respectively,from the pregnancy day 0 to day 17.Female offspring mice were killed to separate serum and collect liver at postpartum day 21. The abortion rate, the survival rate, and the liver index were calculated and the liver histomorphology were observed with hematoxylin-eosin staining (HE). The activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum were detected, and the contents of superoxide dismutase (SOD) and catalase (CAT) in liver were detected by ELISA. The expression of PPARα and its downstream fatty acid oxidation gene were detected by qPCR. The results showed that, compared with the control group, 10 mg·kg-1 PFOA significantly increased the maternal abortion rate (p<0.05), reduced the survival rate of the offspring (p<0.01), and significantly increased the liver index (p<0.01), leading to enlargement of hepatocytes and vacuolization. The levels of AST, ALT, SOD and CAT in PFOA treatment group were significantly up-regulated (p<0.01), and the expression of PPAR-α gene was significantly decreased (p<0.01). The fatty acid oxidation-related genes regulated by PFOA treatment increased significantly (p<0.01).The results showed that exposure to PFOA during pregnancy can increase the rate of maternal miscarriage and postnatal survival. In addition, PFOA treatment can increase liver index, leading to hepatomegaly or even necrosis, activating the progeny female PPAR-α pathway, fatty acid oxidation is exacerbated and reactive oxygen species are deposited, causing oxidative stress and liver damage.

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