不同时程目标温度管理对颅脑创伤大鼠的脑保护作用

Effects of targeted temperature management based on different durations after traumatic brain injury in rats

目的通过延迟低温治疗探讨不同时程目标温度管理对颅脑创伤(traumatic brain injury,TBI)大鼠的脑保护作用。方法36只健康成年雄性SD大鼠随机均分为NT组、HT4h组、HT24h组及HT48h组。采用电子可控性皮质损伤装置制备TBI大鼠模型,NT组于TBI后延迟4 h给予常温(37℃)治疗,实验组于TBI后延迟4 h给予低温(33.0±1.0)℃治疗4、24和48 h。TBI后3 d通过横杆跑动实验和斜坡爬壁实验评估各组大鼠的运动功能,伊文斯兰染色测定血脑屏障透通性,尼氏染色观察海马神经元的变化,免疫荧光/组化染色检测DCX和GFAP表达情况,蛋白免疫印记和免疫组化染色检测Bcl-2和Bax蛋白表达情况。结果与NT组相比,实验组能明显提高TBI大鼠的运动功能,降低血脑屏障透通性,保护海马神经元,促进DCX表达,抑制GFAP表达,上调Bcl-2蛋白的表达,下调Bax蛋白的表达,而在HT48h组的保护作用更显著(P<0.05)。结论长时程的延迟目标温度管理具有显著的脑保护作用。

Objective To investigate the protective effect of target temperature management based different durations with delayed hypothermia for traumatic brain injury(TBI)in rats.Methods 36 healthy adult male SD rats were randomly divided into NT group,HT4h group,HT24h group and HT48h group.The TBI model of rats was prepared with an electronic controllable cortical injury device.NT group was treated with normal temperature(37℃)4 h after TBI,and the experimental groups were treated with low temperature(33.0±1.0℃)4 h after TBI for 4 h,24 h,and 48 h.Three days after TBI,the motor function of the rats in each group was evaluated by beam walking test and inclined-grid climbing test,EB staining was used to measure the blood-brain barrier permeability,the change of hippocampal neurons was observed by Nissl staining,the expression of DCX and GFAP was detected by immunofluorescence,and the expression of Bcl-2 and Bax was measured by Western blot and immunohistochemistry.Results Compared with NT group,the experimental groups could significantly improve the motor function of TBI rats,reduce the permeability of blood-brain barrier,protect hippocampal neurons,promote DCX expression,inhibit GFAP expression,up-regulate the expression of Bcl-2 protein,and down-regulate the expression of Bax protein.However,the protective effect was more apparent in HT48h group than other experimental groups(P<0.05).Conclusion Long-term delayed target temperature management has a significant brain protective effect.