创伤性脑损伤大鼠乙酰胆碱、脑源性神经生长因子表达变化的研究

Researches on the change of expression of acetylcholine and brain-derived neurotrophic factor in rats with traumatic brain injury

目的建立创伤性脑损伤(TBI)模型,探讨创伤性脑损伤大鼠乙酰胆碱(ACh)和脑源性神经生长因子(BDNF)变化及其意义。方法健康雄性SD大鼠192只,随机分为对照组(n=48)和TBI组(n=144)。TBI组随机分为:轻度、中度、重度三组,每组48只。3种TBI组及对照组分别再随机分为15 min、0.5、1、3、6、12、24、48 h各8个亚组,每亚组6只。参照FEENEY′S法制成轻、中、重型颅脑损伤模型。分别于致伤后相应观察时间点取TBI组及对照组海马及皮质等脑组织,用酶联免疫吸附法(ELISA)检测ACh、BDNF在不同脑组织中的含量。结果 TBI中ACh与BDNF海马含量变化呈明显正相关(r=0.340,P<0.01),ACh与BDNF皮质含量变化也呈明显正相关(r=0.311,P<0.01),ACh变化规律是损伤后立即升高,随之迅速下降,降至正常水平以下;BDNF变化规律是损伤后缓慢升高,随之缓慢下降。不同程度TBI组及对照组之间ACh、BDNF脑组织总含量不同,差异有高度统计学意义(P<0.01)。TBI中相同程度不同时间点之间ACh、BDNF脑组织总含量不同,差异有高度统计学意义(P<0.01)。结论 TBI中ACH与BD-NF在脑组织含量变化呈正相关,且与损伤程度有关,通过ACH与BDNF脑组织含量可以间接反映TBI病变及损伤程度,有可能为临床脑损伤的治疗、损伤程度及预后的判断提供新的方法。

Objective To explore the profiles of acetylcholine （ACh） and brain-derived neurotrophic factor （BDNF） in rat models of traumatic brain injury （TBI）. Methods 192 healthy male SD rats were randomly divided into the control group （n = 48） and TBI group （n = 144）. The TBI group was further divided randomly into three secondary groups based on severity of injury （mild, moderate and severe group, each group had 48 cases）. These injury graded groups and control group were again stratified into 8 sub-groups according to time from TBI （15 rain, 0.5, 1, 3, 6, 12, 24 and 48 h）, such that every subgroup had 6 rats. To create TBI models, the rats assigned to injury group were received different powers delivered with reference to FEENEY＇S method immediately after the injury and at specific time spots. Hippocampus and cortex samples were collected from each rat. The brain tissue levels of ACh and BDNF were measured with ELISA. Results There was a positive correlation between post-TBI brain tissue levels of ACh and BDNF （r = 0.340, P 〈 0.01; cortex samples of r = 0.311, P 〈 0.01）. The changes in brain tissue ACh featured by a sudden rise after trauma, a quick decline that ensued and bellowed the normal level. The changes in brain tissue BDNF featured by a gradual rise after trauma, a gradual decline that ensued. The brain tissue levels of Ach and BDNF varied significantly across all groups with different severity of TBI （P 〈 0.01） and time from injury （P 〈 0.01）. Conclusion In traumatic brain injury, both brain tissue levels of Ach and BDNF change regularly to the degree of injury. Detection of brain tissue ACh and BDNF will be helpful to estimate the degree of injury and pathological changes of the traumatic brain injury.