地塞米松预处理对新生鼠缺氧缺血脑损伤的保护作用

Neuroprotection of dexamethasone prophylaxis on brain damage in neonatal rat with hypoxia-ischemia

【目的】观察地塞米松(dexamethasone,DXM)预处理对缺氧缺血新生鼠脑组织兴奋性氨基酸(excitatory amino acid,EAA)和C-fos蛋白表达的影响,探讨不同剂量DXM对新生鼠缺氧缺血性脑损伤(hypoxia-ischemia braindamage,HIBD)的保护作用。【方法】60只新生鼠随机分为4组,假手术组,HIBD组,小剂量DXM预处理组及大剂量DXM预处理组,每组15只。所有动物均于造模后2h断头处死,应用高效毛细管电泳和免疫组化方法,分别检测假手术组、HIBD组、小剂量DXM预处理组(0.5mg/kg)及大剂量DXM预处理组(10mg/kg)的脑组织兴奋性氨基酸(谷氨酸、天门冬氨酸、甘氨酸)含量及C-fos蛋白表达水平。【结果】HIBD组的各种EAA含量及C-fos蛋白表达均较假手术组明显升高(P<0.01);小剂量DXM预处理组的各种EAA含量及C-fos蛋白表达较HIBD组无明显变化(P>0.05);大剂量DXM预处理组EAA含量较HIBD组明显减少(P<0.01),较小剂量DXM预处理组减少(P<0.05);大剂量DXM预处理组C-fos蛋白表达较HIBD组及小剂量DXM预处理组均明显降低(P<0.01)。【结论】缺氧缺血促进脑组织EAA的释放,诱导C-fos蛋白表达;大剂量DXM预处理可能通过抑制EAA释放,降低C-fos蛋白表达而对HIBD起保护作用。

[Objective] To explore the protection of different dose dexamethasone（DXM） prophylaxis for neuronal cell injury and death by observing the effect of DXM prophylaxis on excitatory amino acid （EAA） and C-los protein in the cerebral tissue of neonatal rat with hypoxia-ischemia. [Methods] In this study , hypoxic-ischemic neonatal rat models were established, the levels of EAA（GLU,ASP,GLY）and C-los protein in the cerebral tissue were analysed by using capillary electrophoresis and immunohistochemical method. The rats were divided into four groups： small dose DXM group pretreated with DXM （0.5 mg/kg） prior to hypoxia-ischemia.large dose DXM group pre-treated with DXM（10 mg/kg） prior to hypoxia-ischemia.hypoxia-ischemia brain damage（HIBD） group and shamful operation group. [Results] The levels of EAA contents and C-los protein expressions in HIBD group were significantly higher than those in shamful group （P〈0.01）; there were no significantly difference between HIBD group and small dose DXM prophylaxis group （P〉 0. 05）; EAA contents of large dose DXM prophylaxis group greatly decreased, compared with HIBD group （P〈0.01） ,but compared with small dose DXM prophylaxis group, they were low （P〈0.05）; C-los protein expressions of large dose DXM prophylaxis group were significantly reduced ,compared with HIBD group and small dose DXM prophylaxis group （P〈0.01）. [Conclusions] Hypoxia-ischemia can increase the releases of EAA and induce the expressions of C-fos protein; the pre-treatment Of large dose DXM prior to hypoxia-ischemia is effective in protecting brain cells from further hypoxie-ischemic damage by reducing the EAA＇s releases and inhibiting the C-los protein＇s expressions.