右美托咪碇联合低温对创伤性脑损伤小鼠急性脑水肿的影响  

Effect of dexmedetomidine combined with hypothermia on acute brain edema in mice with traumatic brain injury

作　　者：梁佳敏 张谦 侯亚红 杨程[1] 程世翔[1] Liang Jiamin;Zhmig Qian;Hou Yahong;Yang Cheng;Cheng Shixiang(Brain Center of Characteristic Medical of Chinese People's Armed Police Force, Tianjin Key Laboratory of Neurotrauma Repair, Institute of TBI and Neuroscience, Characteristic Medical Center of Chinese People's Armed Police Force, Tianjin 300162, China;Department of Anesthesiology, Third Medical Center of PLA General Hospital, Beijing 100039, China)

机构地区：[1]武警部队特色医学中心脑科中心,天津市神经创伤修复重点实验室,武警部队特色医学中心脑创伤与神经疾病研究所,天津300162 [2]解放军总医院第三医学中心麻醉科,北京100039

出　　处：《中华创伤杂志》2019年第5期423-429,共7页Chinese Journal of Trauma

基　　金：全军技术产品研究项目(AWS15J001 );天津市临床医学研究中心科技重大专项(15ZXLCSY00040);天津市重点实验室基金(WYKFZ201601 );武警后勤学院附属医院基金(FYZ201505).

摘　　要：目的探讨低温环境下右美托咪碇(Dex)对创伤性脑损伤(TBI)小鼠急性脑水肿的影响.方法180只成年雄性C57B176J小鼠.按随机数字表法分为对照组、假手术组、TBI组、TBI+Dex组、TBI+低温组和TBI+Dex联合低温组,每组30只应用电子控制性脑皮质撞击仪建立TBI模型,假手术组仅开骨窗但不打击,对照组不开骨窗也不打击,TBI+Dex组、TBI+低温组和TBI+Dex联合低温组伤后即刻腹腔注射Dex(60μg/kg,每隔2h给药1次,共3次)和(或)低温干预.TBI组仅致伤,对照组、假手术组均行常温处理并腹腔注射等量生理盐水:伤后24h分别采用甲苯胺蓝、伊文思蓝染色和干湿重法测定各组脑组织损伤体积、血脑屏障通透性和脑组织含水量改变;实时定量PCR和Westernblot法检测损伤区脑组织紧密连接蛋白-5(Claudin-5)mRNA和蛋白表达变化伤后24,48.72h采用改良神经功能缺损评分(mNSS)评价神经功能受损程度:结果与假手术组比较.TB1组伤后24h脑组织损伤体积增加[(0.49±0.04)mm^3;(11.57±1.01)mm^3],血脑屏障通透性升高[(16.4±0.8)p,g/g:(54.3±1.7)μg/g],脑组织含水量增加[(76.7±0.9)%:(83.1±0.8)%],mNSS明显升高[(1.6±0.7)分:(13.4±0.7)分](P均<0.01).TBI+Dex组和TBI+低温组均能减少伤后24h脑组织损伤体积[(7.20±0.18)mm^3和(5.94±0.18)mm^3],降低血脑屏障通透性[(32.7±1.2)μg/g和(27.6±1.0)μg/g],减少脑组织含水量[(78.5±0.4)%和(78.2±0.6)%],降低mNSS[(7.3±1.1)分和(5.8±1.3)分](卩均<0.01)<与TBI+Dex组和TBI+低温组比较,TBI+Dex联合低温组脑组织损伤体积降至(3.92±0.05)mm^3,血脑屏障通透性降至(21.6±0.7)μg/g,脑组织含水量降至(77.7±0.3)%,mNSS降至(4.3±1.2)分(P均<0.01)。伤24h后TIB组Claudin-5mRNA表达较假手术组显著降低(0.93±0.04:0.23±0.01)(P<0.01)与TBI组比较,TBI+Dex组.TBI+低温组和TBI+Dex联合低温组均能上调Claudin-5mRNA表达水平(P<0.01),尤其以TBI+Dex联合低温组升高最为显著(分别为:0.47±0.01,0.54±0.09.0.64±Objective To explore the effect of Dexmedetomidine ( Dex) on acute brain edema in mice in condition with targeted temperature management ( TTM ) following traumatic brain injury ( TBI). Methods A total of 180 male C57BL/6J mice were divided into control group, sham operation group, TBI group, TBI + Dex group, TBI + TTM group, and TBI + Dex + TTM group according to the random number table (n = 30 per group). The sham operation group only opened the bone window but did not hit it, and the control group did not open the bone window. The TBI + Dex, TBI + TTM , and TBI + Dex + TTM groups were intraperitoneally injected with Dex ( 60 μg/kg once eveiy 2 h for 3 times) and/or hypothemiia after TBI. The brain tissue injury volume, EB extravasation and brain water content of each group were determined by toluidine blue, Evans blue staining and dry-wet weight method at 24 hours after injury. Real-time quantitative PCR and Western blot were used to detect the expression of Claudin-5 in the injured brain tissue. At 24, 48 , and 72 hours after injury, the neurological deficiency degree was assessed using the modified neurological severity scores ( mNSS). Results Compared with the sham operation group, TBI mice showed significant increase in brain tissue injury volume [(0.49 ± 0. 04) nim3 us.(11.57 ±1.01) mm^3 ], blood-brain barrier permeability [( 16. 4 ±0. 8)μg/g vs.(54. 3 ±1.7)μg/g], brain tissue water content [(76.7 ±0.9)% vs.(83.1 ±0. 8)%], and mNSS score [(1.6± 0.7) points vs.(13.4 ±0. 7) points] at 24 hour after TBI ( all P < 0. 01 ). However, Dex or TTM treatment reduced brain tissue injury volume [(7.20 ±0. 18) mm3 and (5. 94 ±0. 18) mni3 ], blood-brain bam er permeability [(32. 7 ± 1. 2 )μg/g and ( 27. 6 ± 1. 0 )μg/g ], brain tissue water content [(78. 5 ± 0. 4 )% and (78. 2 ±0. 6)%], and neurological function [ mNSS:(7.3 ±1.1) points and (5. 8 ± 1.3 ) points]( all P < 0. 01 ). Moreover, Dex + TTM group showed better neuroprotection [ reduced brain tissue injury volume:(3. 92 ± 0. 05 ) mm3 , redu

关 键 词：右美托咪呢 脑损伤 脑水肿 低温 紧密连接蛋白-5 

分 类 号：R651.15[医药卫生—外科学]