辛伐他汀对创伤性脑损伤大鼠血清及海马NSE表达的影响

Effects of Simvastatin on Neurone-Specific Enolase Expression in Rats with Traumatic Brain Injury

目的通过观察辛伐他汀对创伤性脑损伤(TBI)大鼠神经元特异性烯醇化酶(NSE)在脑组织和血清中表达的影响,探讨辛伐他汀对大鼠TBI的治疗作用。方法8周龄的SD大鼠90只,随机分为假致伤组、对照组、治疗组,每组30只。对照组、治疗组参照改良的Feeney氏自由落体法制造TBI模型。治疗组大鼠于造模前晚及伤后每晚给予辛伐他汀10 mg/kg灌胃;对照组及假致伤组同时给予等量淀粉灌胃。3组大鼠分别于伤后3 h、12 h、24 h、3 d、7d、14 d取5只大鼠的颈总动脉血3 mL,ELISA法测定NSE浓度;断头取脑,免疫组化法检测伤侧海马CA3区NSE表达。结果 (1)ELISA法测定:对照组,伤后3 h血清NSE即开始升高,24 h至3 d达高峰,14 d仍高于假致伤和治疗组;治疗组,伤后3 h血清NSE水平升高,24 h达高峰,3 d至7 d下降,明显低于对照组,伤后14 d接近假致伤组。(2)免疫组化检测:对照组伤后3 h伤侧海马CA3区NSE光密度值下降,3 d至7 d达低谷,14 d时仍显著低于假致伤组;治疗组的大鼠伤后3 h伤侧海马CA3区NSE光密度值下降,12 h至24 h达低谷,但明显高于对照组,7 d开始回升,14 d时接近假致伤组水平。结论辛伐他汀可促进TBI后血清NSE水平的下降,提高损伤侧海马神经元的NSE表达,对TBI后大鼠损伤的神经元有保护作用。

Objective To study the effect of simvastatin （SIM） on the expression of neuron specific enoalse （NSE） in rat brain and serum after traumatic brain injury （TBI）, and therapeutic effects of SIM on TBI thereof. Methods A total of 90 Sprague-Dwalye （SD） rats aged 8 weeks were randomly divided into sham TBI group, control group and treatment group （n=30）. The TBI model was established in control group and treatment group by using Feeney method. Rats in treatment group were fed SIM 10 mg/kg in the evening pre-injury and in every evening post-injury while those in control group were fed the same dose of starch at the same time. Blood samples （3 mL） were collected from carotid atrery in three groups, then rats were sacrificed and brains were collected at different time points （3 h, 12 h, 24 h, 3 d, 7 d and 14 d post-injury）. The serum ex-pressions of NSE were detected by ELISA method. The NSE expressions in hippocampal area CA3 were detected with immu-nohistochemistry. Results （1） In control group, the serum NSE level was significantly increased at 3 h after injury, reached the peak at 3 d, and was still higher than that of sham injury group at 14 d. In treatment group, the serum NSE level was in-creased 3 h after injury, reached the peak at 24 h, decreased after 3 d, and was near the sham injury group at 14 d after inju-ry, but was significantly lower than that of control group. （2） Immunohistochemical detection showed that the NSE optical density values in hippocampal area CA3 area were decreased at 3 h after injury in control group. The optical density values reached the lowest level between 3 d to 7 d and were still significantly lower than those of sham injury group at 14 d. In treat-ment group the optical density value was decreased at 3 h after injury, reached the lowest level between 12 h to 24 h and re-bounded significantly at 7 d, then at 14 d up to the level of sham injury group. Conclusion SIM can promote the decrease of serum NSE level in TBI rats and increase the NSE expression of hippocampal neurons of injured side, showing protective effects on neuronal damage after traumatic brain injury.