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早期应用地塞米松预防大鼠桥脑中央髓鞘溶解症的发生

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

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【作者】 柯庆宏陈建华郑树森俞军梁廷波

【Author】 KE Qing-hong~(1),CHEN Jian-hua~(2),ZHENG Shu-sen~(1),et al(1.Department of Hepatobiliary and Pancreatic Surgery,The First Affiliated Hospital,College of Medicine,Key Lab of Combined Muti-organ Transplantation,Ministry of Health,Zhejiang University,Hangzhou 310003,China;2.Department of Pathology,The Affiliated Obstetrics and Gynecology Hospiatal,College of Medicine,Hangzhou 310006,China)

【机构】 浙江大学医学院附属第一医院肝胆胰外科卫生部多器官联合移植研究重点实验室浙江大学医学院附属妇产科医院病理科浙江大学医学院附属第一医院肝胆胰外科卫生部多器官联合移植研究重点实验室 浙江杭州310003浙江杭州310006浙江杭州310003

【摘要】 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3 d,第4天腹腔注射1 m o l/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5 m g/kg DEX;DEX延迟治疗组大鼠在注射高渗盐水后24 h肌注5 m g/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;W estern b lot印迹法测定脑内一氧化氮合酶(iN-OS)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0 h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6 h,脑内EB含量比0 h时点明显增加(P<0.05),24 h达高峰,同时脑内iNOS在快速补钠后3 h开始表达增强,36 h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iNOS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iN-OS表达,起到预防CPM的作用。

【Abstract】 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 4th 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.

【基金】 国家重点基础研究发展计划资助项目(2003CB515501);浙江省教育厅基金(No.20030238)
  • 【文献出处】 浙江大学学报(医学版) ,Journal of Zhejiang University(Medical Sciences) , 编辑部邮箱 ,2006年04期
  • 【分类号】R744
  • 【被引频次】6
  • 【下载频次】59
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