异丙酚复合浅低温对大鼠脑创伤后神经细胞凋亡的影响

Effect of propofol-mild hypothermia on apoptosis of neural cells in rats after brain injury

目的本实验通过观察异丙酚复合浅低温治疗后Bax蛋白表达的变化,探讨异丙酚复合浅低温对大鼠脑创伤后神经细胞凋亡的影响.方法采用Feeney′s 脑创伤模型,健康雄性SD大鼠随机分为5组,每组8只:假手术组(S),只颅骨开窗不致伤;模型组(M),制作大鼠脑创伤模型;浅低温组(H),创伤15min后,采用物理降温法,大鼠体温控制在32～34℃(肛温),维持3h;异丙酚组(P),创伤后立即按50mg/kg腹腔注射异丙酚,1h时后追加全量.异丙酚复合浅低温组(PH),既控制性降温,又腹腔注射异丙酚.脑创伤1d后处死大鼠.采用原位缺口末端标记(TUNEL)法检测创伤皮层周围神经细胞凋亡情况,采用免疫组化技术来检测Bax蛋白表达的变化.结果 4组中,M组细胞凋亡数目最多,H组和P组次之,PH组最少.与M组比较,H组、P组Bax表达明显减少(P<0.05、P<0.01);与M组、H组和P组分别比较,PH组Bax表达明显减少(P<0.01、P<0.01、P<0.05).结论脑创伤后创伤灶周围凋亡神经细胞显著增加,异丙酚复合浅低温能显著减少脑创伤后神经细胞凋亡的数量,对脑创伤具有保护作用,这可能是通过调节Bax蛋白的表达来抑制细胞凋亡的.

Objective To explore the effect of propofol-mild hypothermia on the apoptosis of neural cells in rat＇s brain after traumatic brain injury by investigating the expression of Bax in this experiment. Methods By applying Feeney＇s brain injury model, health male SD rats were divided randomly into five groups, eight rats for each group： sham-injured group （S）, only treated with opening the skull without brain injury; model group （M）, treated as Feeney＇s brain injury model; mild hypothermia-treated group （H）, 15rain after brain injury, maintained the body temperature between 32-34℃ （anal temperature） for 3h by physical hypothermia method;propofol-treated group （P）, propofol （50mg/kg） injected intraperitoneally immediately after brain injury, then the same dose was administered after lh; propofol-mild hypothermia-treated group （PH）, propofol injected combined with mild-hypothermia. The rats were killed ldays after brain injury. The number of apoptotic neuron around the injured cerebral cortex was quantified by TUNEL method, the expression of Bax was observed by immunohistochemical staining. Results The quantity of TUNEL （＋） neural cell was the highest in Group M, and Group H and P was higher, and in Group PH was the lowest in four groups. Compared with Group M, the expression of Bax protein in Group H and P was decreased markedly （P〈0. 05, P〈0. 01）. The expression of Bax protein in Group PH was decreased significantly, compared with Group M （P〈0. 01）, and also with Group H and P （P〈0. 05, P〈0. 01）. Conclusion After brain injury, the apoptosis of neural cells around the injured tissue increased significantly. Propofol-mild hypothermia could reduce the apoptosis of neural cells in the injured rat brain tissue, thus could protect the injured brain tissue through its anti-apoptic function by adjusting the expression of Bax.