雌二醇对溴氰菊酯染毒大鼠皮层突触体神经毒性的影响

目的观察雌激素对溴氰菊酯染毒动物皮层突触体膜兴奋性氨基酸递质释放和ATPase活力的影响.方法用高效液相色谱(HPLC)检测不同水平17β-雌二醇(10-5、10-8、10-111mol/L)对2×10-5mol/L溴氰菊酯染毒的去卵巢大鼠皮层突触体氨基酸释放的影响;用化学比色法检测17β-雌二醇(10-5、10-8、10-11mol/L)对2×10-4mol/L溴氰菊酯染毒的去卵巢大鼠皮层突触体Na+-K+ATPase、Mg2+-ATPase、Ca2+-ATPase、Ca2+-Mg2+-ATPage活力的影响,并观察雌激素受体拮抗剂Tamoxifen对雌二醇作用的影响.结果2×10-5mol/L氰菊酯处理可增加高钾去极化状态下大鼠皮层突触体天冬氨酸(Asp)和谷氨酸(Glu)的释放;10-8、10-11mol/L的17β-雌二醇可抑制溴氰菊酯所致高钾去极化状态下突触体Asp和Glu的释放,对Asp释放抑制率为28.42%、24.36%,对Glu释放抑制率为21.52%、14.57%;Tamoxifen对17β-雌二醇的抑制作用未见拮抗.2×10-4mol/L溴氰菊酯可抑制突触体4种ATPage活力;10-5mol/L雌二醇可拮抗溴氰菊酯对4种ATPase活力的抑制;l0-8、10-11mol/L雌二醇可增加Ca2+-ATPase活力;Tamoxifen对雌二醇的拮抗作用仍未见明显影响.结论 17β-雌二醇对溴氰菊酯染毒所致皮层突触体兴奋性氨基酸递质释放增加和ATPase活力抑制有一定的保护作用,该作用可能是雌二醇非基因学机制的表现.

Effects of estradiol on deltamethrin-induced neurotoxicity in rat cerebro-cortical synaptosomes

OBJECTIVE: To investigate the neuroprotective effect of estradiol on the release of excitatory amino acid (EAAs) mediator, and the activity of ATPase in cerebro-cortical synaptosome membrane of rats exposed to deltamethrin. METHODS: Using HPLC to detect EAAs release, and colorimeter method to measure the activities of Na(+)-K(+)-ATPase, Mg(2+)-ATPase, Ca(2+)-ATPase, Ca(2+)-Mg(2+)-ATPase in the cerebro-cortical synaptosomes of ovariectomized rats exposed to deltamethrin (2 x 10(-5)mol/L), and treated with different doses of 17beta estradiol (10(-5), 10(-8), 10(-11) mol/L). Meanwhile, the estrogen receptor (ER) antagonist, tamoxifen, was used to investigate the effect on estradiol. RESULTS: The release of Asp and Glu from the cerebro-cortical synaptosomes was significantly increased by 2 x 10(-5)mol/L deltamethrin exposure at the depolarizing state evoked by 50 mmol/L KCl, while 10(-8), 10(-11) mol/L 17beta estradiol could partly inhibit the effect of deltamethrin on the release of Asp (28.42%, 24.36%, respectively), Glu (21.52%, 14.57%, respectively). The activities of 4 kinds of ATPase were inhibited by 2 x 10(-4) mol/L deltamethrin, and these effects could be blocked by 10(-5) mol/L estradiol, while the activity of Ca(2+)-ATPase was increased by 10(-8), 10(-11) mol/L of estradiol. However, no obvious antagonistic effect of tamoxifen on the function of estradial on EAAs release or the activities of ATPase was found. CONCLUSION: Estradiol showed certain neuroprotective effect on the release of EAAs and the inhibition on ATPase induced by deltamethrin. The effect of estradiol on synaptosomes may indicate the nongenetic mechanism of estradiol.