大剂量地塞米松影响谷氨酸兴奋性神经毒性的在体和离体观察(英文)

EFFECTS OF DEXAMETHASONE ON NEURONAL EXCITATORY TOXICATION OF GLUTAMATE: A COMPARISON BETWEEN THE STUDY IN VIVO AND IN VITRO

研究了大剂量地塞米松对谷氨酸诱发清醒小鼠和离体小鼠原代培养皮层细胞兴奋毒性损伤的影响。小鼠单侧纹状体灌注谷氨酸单钠（ＭＳＧ）引起纹状体内局灶性损伤，此损伤可被６ｍｇ／ｋｇＭＫ－８０１预防。５０ｍｇ／ｋｇ地塞米松每日腹腔注射使该损伤体积增加约１１０±２４．５％。地塞米松还促进ｄｌ－谷氨酸对小鼠原代培养皮层细胞活性的损伤。大剂量地塞米松增加小鼠脂质过氧化产物ＭＤＡ含量，但不增加小鼠不完全性脑缺血所致ＭＤＡ升高，且明显减轻缺血性谷胱甘肽过氧化物酶活性的抑制。对小鼠皮层分离细胞，３μｍｏｌ地塞米松快速并明显加强谷氨酸诱发的细胞内游离钙升高。

The effects of megadose dexamethasone(Dex) on neurotoxication of glutamate in mice and cerebral cortical culture were examined. Unilateral intrastriatum infusion of monosodium glutamate (MSG) produced a localized lesion within striatum in the conscious mice, this lesion was nearly prevented by MK801 6mg/kg , but was increased by (110±24.5)% after pretreatment with Dex 50mg/kg for 5 days. Administration of Dex also facilitated dl glutamate induced viability damage in cultured primary cortical cells. Although forebrain malonaldehyde (MDA) content was increased in Dex pretreated naive mice, Dex did not involve in MDA increase elicited by incomplete brain ischemia, furthermore, it attenuated ischemia induced inhibition in cerebral glutathione peroxidase(GSH px) activity. Dex 3 mmol showed a synergism effect on dl glutamate induced cytosolic free calcium rise in dissociated cortical cells of mice. The present results indicate that megadose glucocorticoids increase the neuronal vulnerability to the excitatory amino acids through a Ca 2+ related rapid mechanism.