颅脑损伤后不同剂量糖皮质激素应用对大鼠继发性脑损伤和死亡率的影响  

Effect of glucocorticoids therapy on mortality and secondary brain injury in rats after traumatic brain injury

作　　者：罗兰兰[1] 陈心[2] 柴艳[2] 江荣才[2] 张建宁[2] 

机构地区：[1]天津市环湖医院心理科,300060 [2]天津医科大学总医院神经外科神经病学研究所,天津300052

出　　处：《中华神经医学杂志》2013年第6期549-554,共6页Chinese Journal of Neuromedicine

基　　金：国家自然科学基金（81000533）;天津市应用基础与前沿技术研究计划（13JCQNJC10500）

摘　　要：目的探讨颅脑损伤后早期应用不同剂量糖皮质激素对大鼠继发性脑损伤和死亡率的影响。方法将成年雄性Wistar大鼠220只按随机数字表法分为正常组、地塞米松正常给药组、甲基强的松龙正常给药组、创伤对照组、小剂量地塞米松组、中剂量地塞米松组、大剂量地塞米松组、小剂量甲基强的松龙组、中剂量甲基强的松龙组和大剂量甲基强的松龙组（后7组统称损伤组），每组各22只。损伤组通过液压打击方法制备成颅脑损伤模型且分别给予生理盐水或不同剂量不同类型糖皮质激素处理，并于伤后24h进行改良神经功能缺损评分。采用TUNEL法于伤后24h、48h、7d和14d时检测各组大鼠损伤侧海马组织的细胞凋亡情况。观察伤后14d内各组大鼠的死亡率，并通过尸检和常规HE染色观察死亡大鼠脑组织、垂体、心脏和肺脏的变化。结果损伤组间伤后24h神经功能缺损评分比较差异无统计学意义俨〉0．05）。损伤组大鼠海马组织中凋亡细胞于伤后24h开始出现，48h达到高峰，7～14d内降至正常，其中大剂量地塞米松组和大剂量甲基强的松龙组凋亡细胞数在伤后48h时均明显高于创伤对照组，差异均有统计学意义（P=O．000，p=-0．002）。大剂量地塞米松组和大剂量甲基强的松龙组的大鼠死亡率也均明显高于创伤对照组，差异均有统计学意义（P=0．012，P=-0．038）。尸检发现大剂量地塞米松组和大剂量甲基强的松龙组的死亡大鼠均有不同程度的间质性肺炎及垂体淤血。结论颅脑损伤可以导致海马神经细胞凋亡，而伤后早期应用大剂量糖皮质激素可进一步加重其凋亡，同时增加死亡率，其原因可能为间质性肺炎和垂体淤血的发生。Objective To investigate the effect of glucocorticoids of different dosages on mortality and hippocampal neuron apoptosis in rats after traumatic brain injury （TBI）. Methods All the adult male Wistar rats were allocated into normal control group, dexamethasone （DXM） treatment group, methylprednisolone （MP） treatment group, injury control group, low-dose DXM treatment group, moderate-dose DXM treatment group, high-dose DXM treatment group, low-dose MP treatment group, moderate-dose MP treatment group, and high-dose MP treatment group （n=22）. Rats in the later seven groups （the injuried groups） accepted fluid percussion injury to induce TBI models, and then, treatments were given. The injury severity was evaluated with modified Neurological Severity Scale 24 h after injury. The number of hippocampal neuron apoptosis was examined using TUNEL aider 24 and 48 h, and 7 and 14 d of injury. The mortality of rats in each group was also observed during a 14-day-follow-up period. The changes of brains, pituitaries, hearts and lungs in the dead rats were examined by H.E. staining. Results No significant difference on the scores of modified Neurological Severity Scale wasnoted in the injuried groups 24 h after the injury （P〉0.05）. The hippocampal neuron apoptosis began to appear 24 h after injury, peaked at 48 h, and declined in 7 to 14 d. At 48 h after injury, the number of hippocampal neuron apoptosis in high-dose DXM treatment and high-dose MP treatment groups was significantly higher than that in the injury control group （P〈0.05）. The mortality of rats in high-dose DXM treatment and high-dose MP treatment was significantly higher than that in the injury control group （P〈0.05）. The autopsy of dead rats in each group revealed various degrees of interstitial pneumonia and hypophysial congestion in rats receiving high-dose glucocorticoids. Conclusion TBI could induce hippocampal neuron apoptosis, and early administration of high-dose glucocorticoids aggravates the apoptosis and increases

关 键 词：颅脑损伤 糖皮质激素 继发性脑损伤 细胞凋亡 间质性肺炎 垂体淤 血 

分 类 号：R651.15[医药卫生—外科学]