摘要目的 研发一种新型爆震伤模拟装置建立小鼠脑爆震伤模型,并研究小鼠脑爆震伤的损伤机制.方法?30只昆明小鼠随机(随机数字法)分为正常对照组(Ctrl组)和脑爆震伤模型组(TBI组).利用自主研发的爆震伤模拟装置制备脑爆震伤小鼠模型,并采用Morris水迷宫、伊文思蓝(EB)实验和HE染色,观察小鼠脑部经冲击波暴露后空间记忆能力、血脑屏障、脑组织病理改变的影响.Western-blot方法检测脑损伤标志物Tau、S100β、胆碱,炎症相关因子IL-1β、IL-4、IL-6、IL-10、NF-κB,凋亡相关因子Bcl-2、Bax、Caspase3和氧化应激相关因子IREα、MDA5、COX2、SOD1和SOD2的蛋白表达.两组间计量资料比较采用成组t检验.结果 与Ctrl组(11.2±2.1)s相比,TBI组小鼠寻找平台时间为(54.6±8.4)s,明显增加(t=-19.330,P<0.05);TBI组小鼠EB渗出量比Ctrl组明显增高3.22倍(t=-13.903,P<0.05);病理染色可见海马区神经元损伤,同时TBI诱导脑组织损伤标志物Tau(0.26±0.03 vs 0.46±0.04,t=-9.788,P<0.05)、S100β(0.54±0.03 vs.0.74±0.02,t=-12.433,P<0.05)和胆碱(0.54±0.05 vs 0.80±0.04,t=-7.970,P<0.05),炎性因子IL-1β(0.22±0.04 vs 0.31±0.05,t=-3.431,P<0.05)、IL-4(0.65±0.02 vs 0.97±0.03,t=-18.927,P<0.05)、IL-6(0.88±0.05 vs 1.07±0.08,t=-9.488,P<0.05)和NF-κB(0.80±0.06 vs 1.03±0.07,t=-4.507,P<0.05),促凋亡因子Caspase-3(0.44±0.03 vs 0.60±0.05,t=-4.472,P<0.05)和Bax(0.66±0.04 vs 0.78±0.04,t=-13.007,P<0.05),促氧化因子IREα(0.72±0.06 vs 1.07±0.04,t=-9.665,P<0.05)、MDA5(0.47±0.02 vs 0.77±0.02,t=-23.678,P<0.05)和COX2(0.70±0.07 vs 0.86±0.02,t=-6.421,P<0.05)的蛋白表达,降低抑炎因子IL-10(1.14±0.06 vs 0.74±0.07,t=13.729,P<0.05)、 抑凋亡因子Bcl-2(0.72±0.05 vs 0.46±0.02,t=11.491,P<0.05)及抑氧化应激因子SOD1(1.17±0.05 vs 0.99±0.01,t=7.731,P<0.05)和SOD2(0.81±0.05 vs 0.61±0.04,t=10.257,P<0.05)的蛋白表达.结论 脑爆震伤可损伤小鼠空间学习记忆能力、破坏血脑屏障、损伤海马区神经元,同时促进脑损伤标志物的表达,诱导炎症反应、氧化应激反应及细胞凋亡的发生,成功通过自主研发的爆震伤模拟装置建立小鼠脑爆震伤模型.

abstractsObjective To develop a new type of blast injury simulator to establish a mouse model of brain blast injury and study its damage mechanism. Methods Thirty healthy Kunming mice were&nbsp;randomly(random number) divided into the normal control group and brain blast injury model (TBI) group. A mouse model of traumatic brain injury was prepared by a self-developed explosive injury simulator. Morris water maze, Evans blue experiment and HE staining were used to observe the effects of shockwave exposure on spatial memory, blood-brain barrier, and pathological changes of brain tissues. T test was used for statistical analysis. Western blot method was used for detecting expression of brain injury markers Tau, S100β, Choline, inflammatory factors IL-1β, IL-4, IL-6, IL-10, NF-κB, apoptosis factors Bcl-2, Bax, Caspase3, and oxide protein stress-related factors IREα, MDA5, COX2 SOD1, and SOD2. Results Compared with the normal control group, (11.2±2.1) s, the time of searching platform in the TBI group was (54.6±8.4) s, was significantly longer (t=-19.330, P<0.05), and the EB exudation in the TBI group was 3.22 times (t=-13.903, P<0.05). Pathological staining revealed neuronal damage in the hippocampus, and TBI induced brain injury markers Tau(0.26±0.03 vs 0.46±0.04,t=-9.788, P<0.05), S100β(0.54±0.03 vs 0.74±0.02,t=-12.433, P<0.05) and Choline(0.54±0.05 vs 0.80±0.04, t=-7.970, P<0.05), inflammatory cytokines IL-1β(0.22±0.04 vs 0.31±0.05,t=-3.431, P<0.05), IL-4(0.65±0.02 vs 0.97±0.03, t=-18.927, P<0.05), IL-6(0.88±0.05 vs 1.07±0.08, t=-9.488, P<0.05) and NF-κB(0.80±0.06 vs 1.03±0.07,t=-4.507, P<0.05), and pro-apoptotic cytokines Bax(0.66±0.04 vs 0.78±0.04, t=-13.007, P<0.05) and Caspase3(0.44±0.03 vs 0.60±0.05, t=-4.472, P<0.05), oxidative stress-related factor pro IREα(0.72±0.06 vs 1.07±0.04, t=-9.665, P<0.05), MDA5(0.47±0.02 vs 0.77±0.02, t=-23.678, P<0.05) and expression of COX2(0.70±0.07 vs 0.86±0.02, t=-6.421, P<0.05), inhibition of inflammation inhibitory factor IL-10(1.14±0.06 vs 0.74±0.07, t=13.729, P<0.05), inhibition of apoptosis factors Bcl-2(0.72±0.05 vs 0.46±0.02, t=11.491, P<0.05) and inhibition of oxidative stress factors SOD1(1.17±0.05 vs 0.99±0.01, t=7.731, P<0.05) and SOD2(0.81±0.05 vs 0.61±0.04, t=10.257, P<0.05) expression. Conclusions The brain injury induced by blast exposure can induce spatial learning and memory loss, blood brain barrier disruption, neuronal damage hippocampus in mice, and promote the expression of brain injury markers, induce inflammation, oxidative stress and apoptosis. The self-developed explosive shock simulator successfully establishes a mouse brain blast injury model.