目的:研究燃煤型氟中毒大鼠学习记忆能力的变化以及氟中毒与B-raf活性等关系.方法:制作氟中毒大鼠模型,以氟斑牙的发生以及脑组织中氟离子浓度评价造模情况,Morris水迷宫空间探索实验检测大鼠学习能力,Western Blot方法检测大鼠脑组织匀浆中B-raf蛋白表达,Realtime PCR法检测大鼠脑组织B-raf活化情况.结果:氟中毒大鼠造模成功,染氟组大鼠逃避潜伏时间均比对照组长,且与染氟剂量相关,提示燃煤型氟中毒大鼠学习能力降低;染氟组大鼠脑组织磷酸化B-raf蛋白和B-raf mRNA水平均高于对照组(P＜0.05),与染氟剂量正相关(r =0.993、0.996),提示染氟组大鼠脑组织B-raf信号通路活化.结论:燃煤染氟饲料可引起慢性氟中毒大鼠学习能力减退,其机制可能与氟中毒大鼠脑组织B-raf信号转导通路的激活、B-raf mRNA表达水平及该蛋白激活磷酸化水平升高有关.%Objective:To investigate the change of learning and memory ability of rats with coal-buring fluorosis and the relationship between fluorosis and activity of B-raf.Methods:Coal-buring fluorosis rat model was established,and he occurrence of dental fluorosis and the fluoride concentration in rats' brain tissue were adopted to evaluate the model.Morris water maze spatial exploration experiment was adopted to test the learning ability of rats.Western blot was used to detect the expression of B-raf protein in rat brain homogenate,and the activity of B-Raf was detected by Realtime PCR.Results:The coal-buring fluorosis rat model was established.Compared with control group,the escape latency of the rats in fluorosis group was significantly longer and correlated with the dose of fluoride,indicating that the learning ability of the rats with fluorosis was reduced.The phosphorylated B-raf protein and Braf mRNA levels in the brain of rats in the fluorosis group were higher than those in control group (P ＜0.05),which was positively correlated with the dose of fluoride (r =0.993,r =0.996).The results suggested that the B-raf signal pathway in the brain of the rats in fluorosis group was activated.Conclusions:Coal-burning pollution feed can cause chronic fluorosis to rats and rats' learning disability,whose mechanism may be related to activation of rat brain's B-Raf signal transduction pathway,elevated expression levels of B-raf mRNA and phosphorylated B-raf protein.
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