摘要
目的探讨慢性氟中毒大鼠脊髓血脑屏障损伤及其机制，并观察脱氟后脊髓血脑屏障损害的恢复情况。方法120只Wistar大鼠驯养1周后随机分为2组，高氟组：30只，饮氟化水（200mg／L）；高氟对照组：30只，饮蒸馏水，脱氟组：30只，先饮氟化水，12周后改为蒸馏水，脱氟对照组：30只，饮蒸馏水。分别于4、8、12周用不锈钢代谢笼收集24h尿液并取测定四组动物尿氟含量，于16、20、24周用同样方法测定脱氟组和脱氟对照组尿氟含量。12周后，将高氟组动物和高氟对照组动物处死，脱氟组动物改饮蒸馏水，24周时将脱氟组及脱氟对照组动物处死，所有动物取颈脊髓置戊二醛固定，备电镜观察。取上胸髓置多聚甲醛固定，石蜡切片，行免疫组织化学染色，取下胸髓行免疫印迹检测基质金属蛋白酶（MMP-9）的含量。并应用Evansblue法进行血脑屏障破坏的定量分析。结果电镜结果发现高氟组及脱氟组动物脊髓星形胶质细胞足突水肿，而脱氟组动物脊髓上述情况无明显恢复；与高氟对照组相比，高氟组动物脊髓EB含量有明显增加，（29．2±0．1）mg／L比（0．7±0．1）mg／L，P〈0．01。脱氟组EB含量较脱氟对照组明显升高，与高氟组对比差异无统计学意义（29．2±0．1）mg／L比（28．9±0．2）mg／L，P〉0．01。高氟组动物脊髓组织中MMP-9与高氟对照组比较表达明显升高，脱氟组脊髓组织中MMP-9表达与脱氟对照组比较明显升高；与高氟组相近。结论慢性氟中毒可导致MMP-9高表达，造成脊髓血脑屏障损害，脱氟后短时间内未能恢复。
Objective To explore the impairment mechanisms of blood brain barrier in spinal cord and observe the changes of matrix metalloproteinase-9 （MMP-9） and functional improvement in rats with chronic fluorosis. Methods A total of 120 Wistar rats were divided randomly into 4 groups, high fluoride （fed by water with a high concentration of sodium fluoride at 200 mg/L）, high fluoride control （fed by distilled water）, defluorination （fed by water with a high concentration of sodium fluoride at 200 mg/L for 12 weeks and then distilled water for 12 weeks） and defluorination control （n = 30 each）. The urinary contents of fluoride were detect for 4 groups at Weeks 4, 8 and 12. The high fluoride and control groups were sacrificed at Week 12 while the defluorination and defluorination control groups at Week 24. Their cervical spinal cords were collected for electron microscope examinations. The expression of MMP-9 protein in thoracic cord was detected by immunohistochemistry and Western blot. Quantitative analysis of function of blood brain cord barrier was performed by the technique of Evans blue. The comparison of measurement data was performed with F test and correlation analysis. The cytological changes of neurons in thoracic spinal cord were detected after chronic fluorosis. Results Under electron microscope, the pathological manifestations of chronic damage in blood brain barrier could be found. As compared with the high fluoride control group, the content of Evans blue increased markedly in spinal cord of the high fluoride group （29. 2 ＋ 0. 1 vs 0. 7 ＋ 0. 1 rag/L, P 〈0. 01 ）. h was higher in the defluorination group than that in the defluorination control group. But there was no significant difference with the high fluoride group （ 29. 2 ＋ 0. 1 vs 28. 9 - 0. 2 mg/L, P 〉 0. 01 ）. And the expression of MMP-9 increased in spinal cord of the fluorosis and defluorination groups in comparison with those in the control group. But no difference existed among them. Conclusion The damage of blood brain barrier of spinal cord occurs probably as a result of a higher expression of MMP-9 in rats with chronic fluorosis. Defluorination for a short time may not recover.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2012年第33期2357-2361,共5页
National Medical Journal of China
基金
基金项目：天津市卫生局科技基金（09KY22）
关键词
氟
中毒
脊髓
血脑屏障
Fluorine
Poisoning
Spinal cord
Blood brain barier
