地卓西平对甲基汞致大鼠脑皮质细胞内钙稳态失调的影响

目的研究地卓西平对甲基汞致大鼠脑皮质细胞内钙稳态失调的影响。方法 Wistar大鼠32只,按体重随机分成4组,每组8只。第1组为对照组,腹腔注射0.9%氯化钠;第2组为低剂量甲基汞染毒组,腹腔注射4μmol/kg的甲基汞溶液;第3组为高剂量甲基汞染毒组,腹腔注射12μmol/kg的甲基汞溶液;第4组为地卓西平预处理组,隔日皮下注射0.3μmol/kg地卓西平,2 h后腹腔注射12μmol/kg的甲基汞溶液;注射容量均为5 ml/kg,染毒4周,每周5次。观察神经细胞内Ca2＋浓度及其凋亡情况,同时测定脑皮质Hg含量和与维持钙稳态相关的酶Na＋-K＋-ATPase和Ca2＋-ATPase活性。结果染毒4周后,随着染毒剂量的增加,脑皮质Hg含量和细胞内Ca2＋浓度均明显升高（P〈0.01）;细胞凋亡率明显高于对照组（P〈0.01）;脑皮质Na＋-K＋-ATPase和Ca2＋-ATPase活性均不同程度的受到抑制。地卓西平预处理可以明显缓解神经细胞凋亡和细胞内Ca2＋超载,对Na＋-K＋-ATPase和Ca2＋-ATPase活性也有一定程度的恢复作用。结论甲基汞通过抑制与维持钙稳态相关的酶Na＋-K＋-ATPase和Ca2＋-ATPase活性,干扰神经细胞内钙稳态,进而造成神经细胞凋亡。地卓西平可以阻断Ca2＋通道对钙稳态失调引起的细胞损伤有拮抗作用。

Effect of Dizocilpine on Intracellular Ca2+ Disorder in Methylmercury Poisoning Rat Cerebral Cortex

Objective To study the impact of dizocilpine on intracellular Ca2+ disorder in methylmercury(MeHg) poisoning rat cerebral cortex. Methods Thirty-two Wistar rats were randomly divided into four groups by body weight(each n=8).The first group was the control group which was given intraperitoneal(i.p.) injection of 0.9% NaCl.The second and third groups were respectively given i.p.injection of 4 and 12 μmol/kg MeHg.The fourth group was dizocilpine pre-treatment group which was given subcutaneous(s.c.) injection of 0.3 μmol/kg dizocilpine every two-day,two hour before the i.p.administration with 12 μmol/kg MeHg.The capacity of injection was all 5 ml/kg.4 weeks after administration,the rats were anatomized to get the tissue samples of the cerebral cortex.By cell apoptosis examination,i,the activity assay of Na+-K+-ATPase and Ca2+-ATPase in rat cerebral cortex,we evaluated the effect of dizocilpine on intracellular Ca2+ disorder in MeHg poisoning rats. Results With the increase of administered-MeHg dosage,there was a significant increase in i and apoptosis rates and decrease in Na+-K+-ATPase and Ca2+-ATPase activities in a concentration-dependent manner.It was suggested that MeHg disturbed intracellular Ca2+ homeostasis.Compared with 12 μmol/kg MeHg group,dizocilpine pre-treatment could decrease i and apoptosis rates and increase Na+-K+-ATPase and Ca2+-ATPase activities. Conclusions MeHg disturbs intracellular Ca2+ homeostasis by inhibiting the activities of Na+-K+-ATPase and Ca2+-ATPase.Dizocilpine may effectively protect MeHg-induced intracellular Ca2+ disorder in a certain extent.