Allopregnanolone与GABA在大鼠大脑的皮层细胞中对kainate诱导乳酸脱氢酶释放的不同作用

目的:观察allopregnanolone与γ氨基丁酸(GABA)对兴奋性毒性的作用.方法:对原代培养大鼠大脑的皮层细胞,采用kainate(KA)处理,诱发兴奋性毒性.通过测定释放至细胞培养基中的乳酸盐脱氢酶(LDH)活性。观察allopregna-nolone与GABA对兴奋性毒性的作用.结果:短期 或长期KA处理,均增加 LDH活性的释放,其作用呈剂量依赖性,EC_(50)值分别为(0.16±0.03)mol/L和(0.257±0.15)mmol/L.短期(3 h)allopreg-nanolone (10-1000 nmol/L)处理对0.2 mmol/L KA诱导的 LDH活性的释放无明显影响.而长期(24 h)allopregnanolone(10-1000 nmol/L)处理抑制KA诱导的LDH活性的释放,其作用呈剂量依赖性,EC_(50)值为(436±19)nmol/L.短期GABA(0.1-100μmo 1/L)处理,加剧KA(0.2 mmol/L)诱导的 LDH活性的释放,其作用呈剂量依赖性,EC_(50)值为(2.7±1.0)μmol/L.长期GABA处理,对KA诱导的LDH活性的释放无明显影响.结论;allopregnanolone和 GABA对KA诱导的兴奋性毒性有不同作用.

Differential effects of allopregnanolone and GABA on kainate-induced lactate dehydrogenase release in cultured rat cerebral cortical cells

AIM: To exam the effects of allopregnanolone and gamma-amino-butyric acid (GABA) on the excitotoxicity. METHODS: The excitotoxicity was evoked by kainate (KA) in the primary culture of rat cerebral cortical cells. Effect of allopregnanolone or GABA on the excitotoxicity was examined by the measurement of lactate dehydrogenase (LDH) activity released in the culture medium. RESULTS: Either acute (3 h) or chronic (24 h) treatment with KA (0.01-1 mmol/L) produced a concentration-dependent increase in LDH activity released. The EC50 values were (0.16+/-0.03) mmol/L and (0.257+/-0.015) mmol/L, respectively. Acute treatment with allopregnanolone (10-1000 nmol/L) for 3 h did not significantly affect the 0.2 mmol/L KA-induced LDH activity. On the other hand, chronic treatment with allopregnanolone (10-1000 nmol/L) for 24 h, produced inhibition on the KA-induced LDH activity in a concentration-dependent manner. The EC50 value was (436+/-19) nmol/L. Acute treatment with GABA (0.1-100 micromol/L) exacerbate the 0.2 mmol/L KA-induced LDH activity in a concentration-dependent manner, with an EC50 value of (2.7+/-1.0) micromol/L; while chronic treatment with GABA had no significant effect. CONCLUSION: There were differential patterns between the effects of allopregnanolone and GABA on the KA-induced excitotoxicity.