研究报告

  • 年未未,汪晓宇,邵丹丹,于秋丽,欧阳玮,章子贵,阮琴.亚慢性氟暴露致小鼠海马损伤的影响及分子机制研究[J].环境科学学报,2018,38(11):4512-4519

  • 亚慢性氟暴露致小鼠海马损伤的影响及分子机制研究
  • Effects of subchronic exposure to fluorine on hippocampal injury in mice and its molecular mechanism
  • 基金项目:国家自然科学基金(No.81573101)
  • 作者
  • 单位
  • 年未未
  • 浙江师范大学化学与生命科学学院, 金华 321004
  • 汪晓宇
  • 浙江师范大学化学与生命科学学院, 金华 321004
  • 邵丹丹
  • 浙江师范大学化学与生命科学学院, 金华 321004
  • 于秋丽
  • 浙江师范大学化学与生命科学学院, 金华 321004
  • 欧阳玮
  • 浙江师范大学体育与健康科学学院, 金华 321004
  • 章子贵
  • 浙江师范大学行知学院, 金华 321004
  • 阮琴
  • 浙江师范大学行知学院, 金华 321004
  • 摘要:为探明亚慢性氟中毒致小鼠海马损伤及分子机制,选用ICR雄性小鼠140只,随机分为对照(C)、低氟(LF)、高氟(HF)、低氟(LF)+L钙离子通道激动剂(FPL)、低氟(LF)+L钙离子通道抑制剂(NIF)、高氟(HF)+激动剂(FPL)、高氟(HF)+抑制剂(NIF)7组,分别饮用自来水、5、30 mg·L-1氟化钠水溶液90 d,氟染毒第84 d分别腹腔注射生理盐水、FPL64176、Nifedipine7d.同时,采用开场行为及水迷宫检测学习记忆能力;通过HE切片染色观察海马形态结构;根据试剂盒说明检测脑组织谷胱甘肽过氧化物酶(GSH-PX)、总超氧化物歧化酶(SOD)酶活性及丙二醛(MDA)含量;利用RT-PCR和Western Blot法分别检测海马内凋亡相关分子CaMKⅡ和Bax、Bcl-2基因/蛋白表达.结果发现,HF组、LF+FPL组和HF+FPL组小鼠毛发粗糙,暴躁不安.LF、HF组小鼠自发活动、探究行为及空间学习记忆力显著下降(p<0.05),海马细胞损伤,SOD、GSH-PX活性极显著下降(p<0.01),CaMKⅡ基因/蛋白表达水平显著(p<0.05)或极显著(p<0.01)上调,Bax基因/蛋白表达水平显著(p<0.05)或极显著(p<0.01)上调,Bcl-2基因/蛋白表达水平显著(p<0.05)或极显著(p<0.01)下调,Bax与Bcl-2基因/蛋白表达水平比值显著(p<0.05)或极显著(p<0.01)上调;LF+FPL、HF+FPL处理加剧了上述基因/蛋白表达水平,LF+NIF、HF+NIF组可逆转上述基因/蛋白表达水平.结果提示,氟中毒致脑损伤与L型钙离子通道及下游相关分子表达异常密切相关,而L钙离子通道抑制剂(Nifedipine)能改善氟暴露造成的海马损伤.
  • Abstract:To study the hippocampus damage mechanism following subchronic fluorosis exposure in mice. 140 ICR male mice were randomly fed with free drinking tap water containing less than 0.5 mg·L-1 (control), 5 mg·L-1 (LF), and 30 mg·L-1 (HF) fluoride (NaF) for 90 days. At day 84 following exposure to fluorine; the mice were treated with FPL64176 (LF+FPL, HF+FPL) or nifedipine (LF+NIF, HF+NIF) ip. The open field and the water maze were used to detect learning and memory, and hippocampal morphological structure was observed. Glutathione peroxidase (GSH-PX), total superoxide dismutase (SOD) enzyme activity, and malondialdehyde (MDA) in brain tissue were detected according to kit instructions. RT-PCR and Western blot were separately used to detect CaMKⅡ, Bax and Bcl-2 Genes/protein in the hippocampus. Mice in group HF, group LF+FPL and group HF+FPL had rough, irritable hair. Spontaneous activity, inquiried spatial learning and memory decreased significantly in mice of low fluorine group and high fluoride group compared to the control group (p<0.05). The injuried hippocampal cell, the decreased activity of GSH-PX (p< 0.01), up-regulated expression levels of CaMKⅡ (p<0.05) and Bax (p<0.05 or p<0.01), down-regulated Bcl-2 (p<0.05 or p<0.01) gene/proteinthe, and the increased ratio of Bax and Bcl-2 (p<0.05 or p<0.01)were found. FPL64176 aggravated and nifedipine reversed these changes induced by fluorine exposure. The brain injury induced by fluoride exposure is closely related to L-type calcium channel and downstream signal, and block of L-type calcium channel can improve the hippocampal damage caused by fluorine exposure.

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