长时程亚低温通过抑制颅内压反弹促进颅脑创伤大鼠的神经保护作用  

Long-term mild hypothermia promotes neuroprotection by antagonizing the rebound of intracranial pressure after traumatic brain injury in rats

作　　者：赵万勇 李晓红 王景景 孙洪涛 ZHAO Wanyong;LI Xiaohong;WANG Jingjing;SUN Hongtao(Department of Neurosurgery,Qilu Hospital of Shandong University Dezhou Hospital,Dezhou 253000,China;Institute of Medical Engineering and Translational Medicine,Tianjin University;Tianjin Key Laboratory of Neurotrauma Repair,Institute of Neurotrauma Repair,Characteristic Medical Center of People's Armed Police Forces)

机构地区：[1]山东大学齐鲁医院德州医院神经外科,253000 [2]天津大学医学工程与转化医学研究院 [3]武警特色医学中心神经创伤修复研究所,天津市神经创伤修复重点实验室

出　　处：《天津医药》2024年第1期68-73,共6页Tianjin Medical Journal

基　　金：国家自然科学基金面上项目(32070791)。

摘　　要：目的 探索长时程亚低温(MHT)治疗颅脑创伤(TBI)大鼠的最佳持续时间,并观察其对颅内压(ICP)变化和神经功能恢复的影响。方法 48只健康成年雄性SD大鼠采用随机数字表法分为常温治疗(NT)组、MHT4 h组、MHT24 h组和MHT48 h组,每组12只。制备大鼠TBI模型并植入ICP监测探头。造模完成后NT组给予常温(37℃)维持,其余组分别给予低温(33.0±1.0)℃治疗4 h、24 h和48 h。监测各组MHT治疗结束后的ICP并计算脑组织含水量(BWC);伊文斯兰(EB)染色测定血脑屏障透通性;免疫荧光染色检测5-溴脱氧尿嘧啶核苷(BrdU)、神经元核抗原抗体(NeuN)和白细胞分化抗原86(CD86)表达情况;Western blot法检测B细胞淋巴瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、诱导型一氧化氮合成酶(iNOS)、白细胞介素(IL)-10和精氨酸酶1(Arg-1)蛋白表达情况。结果 与NT组相比,MHT4 h组、MHT24 h组和MHT48 h组BWC、ICP、EB水平、CD86阳性细胞数,Bax、iNOS表达水平降低,海马区BrdU阳性细胞数和BrdU/NeuN双标记阳性细胞数增多,Bcl-2、IL-10和Arg-1表达水平升高(P<0.01);与MHT24 h组比较,MHT48 h组BWC、ICP、EB水平、CD86阳性细胞数,Bax、iNOS表达水平降低,BrdU阳性细胞数和BrdU/NeuN双标记阳性细胞数增多,Bcl-2、IL-10和Arg-1表达水平升高(P<0.01)。结论 长时程MHT能够通过抑制ICP反弹,促进神经元的增殖和分化,抑制细胞凋亡和减轻炎症反应,促进TBI后的神经保护作用。Objective To explore the optimal duration of long-term mild hypothermia(MHT)for traumatic brain injury(TBI)in rats,and observe its effect on intracranial pressure(ICP)and neurological function.Methods Forty-eight healthy adult male SD rats were divided into the normal temperature treatment(NT)group,the MHT4 h group,the MHT24 h group and the MHT48 h group by random number table method,with twelve rats in each group.The TBI model of rats was prepared by electronic controllable cortical injury device,and ICP monitoring probe was implanted.After modeling,the NT group was treated with normal temperature(37℃),and the other groups were treated with low temperature(33.0±1.0)℃for 4 h,24 h and 48 h,respectively.ICP was monitored and brain water content(BWC)was calculated after MHT treatment in each group.Blood-brain barrier permeability was determined by Evansland(EB)staining.The expression of 5-bromodeoxyuracil nucleoside(BrdU),neuronal nuclear antigen antibody(NeuN)and leukocyte differentiation antigen 86(CD86)positive cells were detected by immunofluorescence staining.The expressions of B-cell lymphoma-2(Bcl-2),Bcl-2 associated X protein(Bax),inducable nitric oxide synthase(iNOS),interleukin(IL)-10 and arginase 1(Arg-1)were detected by Western blot assay.Results Compared with the NT group,levels of BWC,ICP,EB,and CD86 positive cells,Bax and iNOS expression levels were decreased in the MHT4 h group,the MHT24 h group and the MHT48 h group,and the number of BrdU positive cells and BrdU/NeuN double-labeled positive cells were increased in hippocampus.The expression levels of Bcl-2,IL-10 and Arg-1 were increased(P<0.01).Compared with the MHT24 h group,levels of BWC,ICP and EB,and CD86 positive cells,Bax and iNOS expression were decreased,and the number of BrdU positive cells and BrdU/NeuN double-labeled positive cells were increased in the MHT48 h group,while levels of Bcl-2,IL-10 and Arg-1 expression were increased(P<0.01).Conclusion Long-term MHT can promote the proliferation and differentiation of neurons,inhibit apo

关 键 词：颅脑损伤 颅内压 低温 人工 血脑屏障 亚低温 长时程 

分 类 号：R651.15[医药卫生—外科学]