去铁胺对大鼠脑冲击伤后脑组织自噬损伤的影响  

Effect of deferoxamine on autophagy induction after blast-induced brain injury in rats

作　　者：张礼均[1] 胡荣[2] 李飞[2] 孟辉[2] 林江凯[2] 朱刚[2] 冯华[2] 

机构地区：[1]重庆市急救医疗中心神经外科,400014 [2]第三军医大学西南医院神经外科

出　　处：《中华创伤杂志》2015年第8期748-752,共5页Chinese Journal of Trauma

基　　金：国家自然科学基金资助项目（30901545,30872674）;重庆市卫生局医疗特色专科资助项目[渝卫科教（2010）52号]

摘　　要：目的探讨去铁胺对大鼠脑冲击伤后脑组织白噬损伤的影响。方法选择健康成年雄性SD大鼠39只，按随机数字表法分为假手术组、致伤组和去铁胺治疗组，每组13只大鼠。参照Feeney法建立大鼠脑冲击伤模型，致伤后2h分别予以等量等渗盐水及去铁胺（100mg／kg）腹腔注射，间隔12h给药，持续28d。并于伤后1，3，7，14，28d检测大鼠血红蛋白、肛温、血糖和死亡率。动物处死前完成Morris水迷宫实验，后取大鼠大脑标本计算大脑缺损体积。取致伤灶周围脑组织，采用免疫组化和Western blot方法检测Beclin1的表达。结果各组大鼠同一时相点血红蛋白、肛温、血糖差异均无统计学意义（P〉0．05），致伤组和去铁胺治疗组死亡率差异无统计学意义；去铁胺治疗组大脑缺损体积为（115．35±13．70）mm^3，较致伤组的（209．99±16．70）mm明显减小（P〈0．05）；Morris水迷宫试验显示，去铁胺治疗组动物平台搜索策略（3．13±0．35）和搜索时间[（36．15±26．63）s]均较致伤组[分别为2．13±0．64和（110±47．34）s]显著改善（P〈0．05）；免疫组化显示，致伤后Beclin1表达显著上调，予去铁胺治疗后，Beclin1显著下调；进一步Western blot定量检测显示，伤后Beclin1表达显著增强（P〈0．05），去铁胺治疗后，其表达显著下调（P〈0．01）。结论大鼠大脑冲击伤后Beclin1表达上调，提示脑冲击伤后自噬损伤增强，去铁胺的治疗效果可能是通过减轻自噬损伤来实现的。Objective To determine the effect of deferoxamine administration on autophagy in a rat model of blast-induced brain injury. Methods Thirty-nine male SD rats were allotted to shamoperated group, injury group and deferoxamine group with 13 rats in each, according to the random number table. Feeney ＇s method was applied to establish the model. Deferoxamine group received deferoxamine of 100 mg/kg intraperitoneally. Sham-operated and injury group were injected with saline intraperitoneally. All treatments were started two hours postinjury at 12 hour interval for up to 28 days. Hemoglobin, rectal temperature, blood glucose and mortality were detected at 1, 3, 7, 14 and 28 days. Morris water maze was conducted. Rats were killed later for detecting the brain defect volume and level of Beclin 1 at the site of injury. Results There were no significant differences among the three groups with respect to hemoglobin, rectal temperature and blood glucose （P 〉 0.05 ）. Mortality in injury versus deferoxamine groups did not differ significantly （ P 〉 0.05 ）. Volume of defected brain in deferoxamine group was （ 115.35± 13.70） mm^3, smaller than （209.99 ± 16.70） mm^3 in injury group （P 〈 0.05 ）. In Morris water maze test, the time spent in the searching the platform and latency to reach the platform were improved in deferoxamine group compared to those in injury group [ （3.13 ±0.35） vs （2.13 ±0.64） ; （36.15±26.63 ）s vs （110± 47.34） s respectively] （P 〈 O. 05 ）. Both immunohistochemisty and western blot showed dramatically increased level of Beclin 1 after injury, but treatment with deferoxamine significantly reduced the Beclin 1 expression. Conclusion Level of Beclin 1 is significantly upregulated after blast-induced brain injury in rats, resulting in elevated autophagy postinjury, but the treatment with deferoxamine is neuroprotective possible by lessening autophagy damage.

关 键 词：脑损伤 自噬 去铁胺 

分 类 号：R651.15[医药卫生—外科学]