慢性氟中毒对大鼠肝、肾和脑皮质细胞线粒体DNA4．8kb的影响

Effects of chronic fluorosis on 4.8 kb mitochondrial DNA in liver, kidney and brain of rats

目的观察慢性氟中毒对大鼠肝、肾和脑皮质细胞线粒体DNA4．8kb大片段的影响，探讨线粒体氧化呼吸链在慢性氟中毒发病机制中的作用。方法将60只SD大鼠按体质量随机分为3组（每组20只）：对照组、低氟组和高氟组，分别饮用加入0、10、50mg／L氟化钠的自来水。6个月时．采用实时荧光定量PCR方法检测大鼠肝、肾、脑皮质细胞线粒体DNA4．8kb存在水平。结果低、高氟组大鼠肝脏（2．1X10-3、1．6×10-3）、肾脏（1．7×10-3、1．4×10-4）和脑皮质（1．5×10-5、1．3×10-5）细胞线粒体DNA4．8kb存在水平较对照组（2．9×10-3、2．0×10-3、1．1×10-4）明显下降（P均〈0．05），且高氟组肾脏DNA4．8kb存在水平较低氟组明显降低（P〈0．05）。结论慢性氟中毒可导致大鼠肝、肾和脑皮质细胞线粒体DNA4，8kb大片段缺失，造成线粒体DNA结构受损，引起线粒体氧化呼吸链障碍。

Objective To investigate the deletion pattern of 4.8 kb mitochondrial DNA（mito-DNA） in liver, kidney, and brain of rats with chronic fluorosis and to explore the significance of mitochondria in the pathogenesis of chronic fluorosis. Methods Sixty SD rats were randomly divided into 3 groups according to body mass （20 in each group）： control, low-fluoride and high-fluoride groups, and they were fed with different concentrations of fluoride in drinking water （0, 10, 50 mg/L, respectively） for 6 months. Mito-DNA in liver, kidney and brain was detected by real-time PCR. Results The amounts of 4.8 kb mito-DNA in liver（2.1 ~ 10-3, 1.6 ~ 10-3）, kidney （1.7 ＂x 10-3, 1.4 x 10-4） and brain cortex （1.5 ~ 10-s, 1.3 ~ 10-5） in low- and high-fluoride groups were significantly reduced, as compared with that of control group （2.9 × 10-3, 2.0 × 10-3, 1.1 × 104, all P〈 0.05）. The amount of 4.8 kb mito-I）NA in kidney in high-fluoride group was lower than that in low-fluoride group （P 〈 0.05）. Conclusions Excessive fluoride intake can result in missing of 4.8 kb mito-DNA in liver, kidney and brain cortex. The abnormal of mito-DNA might be related to the dysfunction of mitochondrial respiratory chain.