早期应用地塞米松预防大鼠桥脑中央髓鞘溶解症的发生

目的：探讨地塞米松（DEX）对大鼠中央髓鞘溶解症（CPM）的预防作用及机理。方法：通过皮下注射长效尿崩停针和腹腔注射2．5％葡萄糖液诱导大鼠低钠血症3d，第4天腹腔注射1mol／L氯化钠液（高渗盐水）快速补钠的方法诱导大鼠CPM模型。DEX早期治疗组大鼠在注射高渗盐水同时肌注5mg／kg DEX；DEX延迟治疗组大鼠在注射高渗盐水后24h肌注5mg／kg DEX；生理盐水治疗组大鼠在注射高渗盐水同时肌注生理盐水；另设正常对照组。观察大鼠脑组织脱髓鞘病变发生情况；测定脑内伊文思兰（EB）的含量变化；Western blot印迹法测定脑内一氧化氮合酶（iNOS）的表达变化。结果：通过诱导低钠血症、快速补钠的方法成功建立了大鼠CPM模型。DEX早期治疗组、DEX延迟治疗组、生理盐水治疗组3组大鼠在快速补钠后0h时点，脑内EB含量与正常对照组无明显差异（P〉0．05）。生理盐水治疗组大鼠在快速补钠后6h，脑内EB含量比0h时点明显增加（P〈0．05），24h达高峰，同时脑内iNOS在快速补钠后3h开始表达增强，36h仍呈较强表达，脱髓鞘发生率为66．7％。DEX早期治疗组大鼠快速补钠后脑内EB含量及iN0s表达，均较同时点生理盐水治疗组明显下降，未见明显脱髓鞘病变。DEX延迟治疗组脱髓鞘病变发生率为75％，与生理盐水治疗组无明显差异（P〉0．05）。结论：早期应用DEX能够通过保护血脑屏障和抑制脑内iNOS表达，起到预防CPM的作用。

Prevention of central pontine myelinolysis in rats by early treatment with dexamethasone

Objective: To explore the effect and mechanism of dexamethasome(DEX) in the prevention of central pontine myelinolysis(CPM) in rats.Methods: Hyponatremia was induced in rat by subcutaneous injection of Vasopressin Tannate and intraperitoneal injection of 2.5% dextrose in water for 3 d,the rats of Group A received a bolus of 1mol/L NaCl(2ml/kg) and DEX(5mg/kg) simultaneously at the 4~(th) day;the rats of Group B were treated with DEX after 24 h of the injection of 1mol/L NaCl;the rats in Group C received a bolus of 1mol/L NaCl and saline simultaneously;Group D was the control group.The demyelinative lesions were evaluated by myelin staining.The Evans blue(EB) contents of brain were detected to evaluate the blood-brain(-barrier) permeability after rapid correction of hyponatremia.The expression of inducible nitric oxide synthase(iNOS) in brains was evaluated by Western blotting.Results: CPM was induced successfully in rats.The EB contents of Group A,B and C had no significant difference at 0 h after injection of hypertonic saline compared with Group D.The EB contents of Group C began to increase significantly at 6 h after injection of hypertonic saline,peaked at 24 h;the expression of iNOS in brains began to increase after 3 h after the rapid correction of hyponatremia.The rate of morbidity in Group C was 66.7%.The demyelinative lesions were rarely seen in Group A,the EB contents of brain decreased significantly compared with Group C at the same time point(P<0.05),the iNOS expression was also inhibited.DEX could not prevent the attack of CPM at Group B,the rate of morbidity(75%) had no significant difference compared with Group C(P>0.05).Conclusion: Early treatment with DEX can protect blood-brain-barrier and inhibit the expression of iNOS to prevent the attack of CPM.