甲基强的松龙对脑创伤后大鼠下丘脑室旁核神经元的双重作用

Dual function of methylprednisolone on paraventricular nucleus neurons after traumatic brain injury in rats

目的 探讨甲基强的松龙（methylprednisolone,Mp）对创伤性脑损伤（traumatic brain injury,TBI）后下丘脑室旁核（paraventricular nucleus,PVN）神经元凋亡的影响. 方法 185只Wistar成年雄性大鼠按随机数字表法分为假手术组20只,创伤对照组45只,小剂量MP治疗组50只,大剂量MP治疗组70只.采用液压打击方法制作大鼠TBI模型.分别采用TUNEL标记、免疫组织化学以及透射电镜等方法检测PVN神经元细胞的数量及凋亡情况. 结果 假手术组大鼠PVN罕见凋亡神经元（0.7±1.6）,创伤对照组PVN凋亡细胞伤后7d达到高峰（36.4±18.8）,相应促肾上腺激素释放激素（corticotropin-releasing hormone,CRH）阳性细胞达到低谷（208.0±19.8）.与创伤对照组比较,大剂量MP明显增加了神经元凋亡数量（70.7±27.2）（P＜0.05）,明显减少了大鼠CRH阳性神经元数量（141.7 ±32.6） （P ＜0.05）,明显增加了大鼠短期死亡率（55％）（P＜0.05）;相反,小剂量MP明显减少了PVN神经元凋亡数量（17.6±6.9）（P＜0.05）,明显增高了CRH阳性神经元数量（249.2±20.3） （P ＜0.05）,降低了大鼠短期死亡率（10％）. 结论 TBI后大剂量MP能加重PVN神经元损伤,增加大鼠近期死亡率,而小剂量MP对伤后PVN神经元起保护作用,减少死亡率.

Objective To investigate the effect of methylprednisolone （MP） therapy on apoptosis of neurons in the paraventricular nucleus （PVN） after traumatic brain injury （TBI） in rats.Methods A total of 185 Wistar rats were divided into sham operation group （n =20）,trauma control group （n =45）,low-dose MP therapy group （n =50） and high-dose MP therapy group （n =70）,according to the random number table.TBI models were induced by fluid percussion injury.TUNEL staining,immunohistochemistry and transmission electron microscope were used to detect PVN neuron number and apoptosis.Results Apoptotic neurons in the PVN were 0.7 ± 1.6,rare in sham operation group,whereas apoptotic neurons in trauma control group were firstly detected at 3 days and reached peak at 7 days （36.4 ± 18.8）,with a slump of corticotropin-releasing hormone （CRH） for 208.0 ± 19.8.High-dose MP therapy markedly increased the neuron apoptosis （70.7±27.2）,reduced CRH-positive cells （141.7 ±32.6）,and increased short-term mortality （55%） when compared to trauma control group （all P 〈 0.05）.In contrast,low-dose MP greatly reduced PVN neuron apoptosis （17.6 ± 6.9）,but increased CRH-positive cells （249.2 ±20.3） （P〈0.05） and decreased the short-term mortality （10%）.Conclusions High-dose MP therapy increases neuronal apoptosis in PVN and short-term mortality after TBI.However,low-dose MP protects PVN neurons against TBI-induced apoptosis and reduces the mortality.