目的 研究亚低温(MHT)联合促红细胞生成素(EPO)对颅脑创伤(TBI)大鼠脑保护的作用及其机制.方法 根据是否接受MHT(32 ~33℃,4h)、腹腔注射EPO(5 000 U/kg)治疗,将80只雄性Wistar大鼠按随机数字表法分为假手术组、常温治疗组、MHT组、EPO组、MHT+ EPO组,每组16只,颅脑创伤模型参照液压打击法制作,采用神经功能缺陷评分量表进行神经功能评分、利用干/湿重法检测脑组织含水量、Evans蓝测定法检测BBB通透性、HE染色比较颅脑创伤大小、RT-PCR及Western blot法检测Claudin-5表达水平.结果 MHT及EPO均可降低颅脑创伤大鼠神经功能缺陷评分,减轻脑组织水肿,降低血脑屏障(BBB)通透性,上调Claudin-5的表达水平(均P<0.05).结论 MHT、EPO对颅脑创伤大鼠均有脑保护作用,且两种治疗联合应用脑保护作用更加显著.上调Claudin-5的表达水平是其发挥脑保护作用的机制之一。
Objective To study the protective mechanism of mild hypothermia (MHT) and erythropoietin (EPO) therapy on traumatic brain injury (TBI) rats.Methods Eighty male Wistar rats were randomly divided into sham-operated group (Sham),normothermic treatment following TBI group (NT),mild hypothermia group (MHT),EPO group (EPO),and combined group (MHT + EPO),respectively.The TBI animal models were established according to fluid percussion impact (FPI) method.The neurological deficit was evaluated using a modified neurological severity score (mNSS) at 48 h after FPI.The changes of brain water content and permeability of blood-brain barrier were measured by the methods of wet and dry weight and Evans blue stain.The sizes of injury lesion were evaluated by hematoxylin and eosin (HE) stain.Western blotting and RT-PCR were used to analyze the expression of Claudin-5.Results Both MHT and EPO treatment lessened the neurological deficit scores.The brain water content,lesion size and attenuate BBB permeability and the expression of Claudin-5 were observed (P 〈 0.05).Conclusions Both MHT treatment and EPO treatment could express neuroprotective effect for TBI rats.This protective effect against TBI might be achieved by upregulation of Claudin-5.