• 关键词：氟中毒  Morris水迷宫  脑海马  组织结构  部分氧化及抗氧化酶  Bax  Bcl-2  CaMKⅡ

• 基金项目：国家自然科学基金（No.81573101）

• 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.

• Key words：fluorosis  morris water maze  hippocampus  tissue structure  partial oxidation and antioxidant oxidase  Bax  Bcl-2  CaMKⅡ

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