中华急诊医学杂志
中華急診醫學雜誌
중화급진의학잡지
CHINESE JOURNAL OF EMERGENCY MEDICINE
2009年
1期
17-21
,共5页
何志捷%黄子通%邹子俊%陈晓彤%王彤
何誌捷%黃子通%鄒子俊%陳曉彤%王彤
하지첩%황자통%추자준%진효동%왕동
心肺复苏%血脑屏障%基质金属蛋白酶%MMP-9抑制剂%脑组织损伤
心肺複囌%血腦屏障%基質金屬蛋白酶%MMP-9抑製劑%腦組織損傷
심폐복소%혈뇌병장%기질금속단백매%MMP-9억제제%뇌조직손상
Cardiopulmonary resuscitation%Blood brain barrier%Matrix metallopmteinase%MMP.9 inhibitor%Brmn tissue damage
目的 探讨心肺复苏早期大鼠脑组织基质金属蛋白酶-9(MMP-9)的表达和血脑屏障的变化规律及MMP-9抑制剂SB-3CT的作用.方法 将健康Sprague-Dawley(SD)雄性大鼠120只随机分为假手术对照组、复苏对照组和复苏治疗组,实验地点在中山大学北校区动物实验中心.动物模型采用气管夹闭窒息法,自主循环恢复定义为恢复室上性心律,平均动脉压≥60mmHg并且维持5 min以上.假手术对照组仅进行麻醉和气管插管,复苏治疗组于自主循环恢复后立即腹腔内注射SB-3CT 25mg/kg.复苏对照组于自主循环恢复后不注射SB-3CT.在即刻及3,9,24 h和48 h时间点分5个时间点处死大鼠后,取样,测定脑组织MMP-9蛋白的表达和检测腩组织MMP-9 mRNA,观察脑含水量和伊文思蓝含量的变化,使用电镜观察脑组织的超微结构.统计分析采用方差分析法.结果 假手术对照组脑组织MMP-9表达、MMP-9 mRNA、脑含水量和伊文思蓝含量在各时间点均无明显变化,p 值分别为1.0000,0.6831,0.7124和0.9975.复苏对照组心肺复苏后上述指标均明显变化在24 h到达高峰,P 值分别为0.0264,0.0163,0.0000和0.0412,与假手术组比较有统计学意义.复苏治疗组心肺复苏后上述指标变化与复苏对照组相似,但变化程度较复苏对照组轻,P 值分别为0.0392,O.0373,0.O004和O.0180.脑组织损伤情况通过电镜观察得到证实.结论 大鼠心肺复苏后脑MMP-9,MMP-9 mRNA、脑含水量和伊文思蓝含量明显升高,血脑屏障受到破坏;电镜观察证实脑组织损伤明显;这些变化在心肺复苏后24 h时点达高峰.应用特异性MMP-9抑制剂SB-3CT可显减少MMP-9的表达,减轻脑水肿,对心肺复苏后脑缺血-再灌注损伤有明显保护作用.
目的 探討心肺複囌早期大鼠腦組織基質金屬蛋白酶-9(MMP-9)的錶達和血腦屏障的變化規律及MMP-9抑製劑SB-3CT的作用.方法 將健康Sprague-Dawley(SD)雄性大鼠120隻隨機分為假手術對照組、複囌對照組和複囌治療組,實驗地點在中山大學北校區動物實驗中心.動物模型採用氣管夾閉窒息法,自主循環恢複定義為恢複室上性心律,平均動脈壓≥60mmHg併且維持5 min以上.假手術對照組僅進行痳醉和氣管插管,複囌治療組于自主循環恢複後立即腹腔內註射SB-3CT 25mg/kg.複囌對照組于自主循環恢複後不註射SB-3CT.在即刻及3,9,24 h和48 h時間點分5箇時間點處死大鼠後,取樣,測定腦組織MMP-9蛋白的錶達和檢測腩組織MMP-9 mRNA,觀察腦含水量和伊文思藍含量的變化,使用電鏡觀察腦組織的超微結構.統計分析採用方差分析法.結果 假手術對照組腦組織MMP-9錶達、MMP-9 mRNA、腦含水量和伊文思藍含量在各時間點均無明顯變化,p 值分彆為1.0000,0.6831,0.7124和0.9975.複囌對照組心肺複囌後上述指標均明顯變化在24 h到達高峰,P 值分彆為0.0264,0.0163,0.0000和0.0412,與假手術組比較有統計學意義.複囌治療組心肺複囌後上述指標變化與複囌對照組相似,但變化程度較複囌對照組輕,P 值分彆為0.0392,O.0373,0.O004和O.0180.腦組織損傷情況通過電鏡觀察得到證實.結論 大鼠心肺複囌後腦MMP-9,MMP-9 mRNA、腦含水量和伊文思藍含量明顯升高,血腦屏障受到破壞;電鏡觀察證實腦組織損傷明顯;這些變化在心肺複囌後24 h時點達高峰.應用特異性MMP-9抑製劑SB-3CT可顯減少MMP-9的錶達,減輕腦水腫,對心肺複囌後腦缺血-再灌註損傷有明顯保護作用.
목적 탐토심폐복소조기대서뇌조직기질금속단백매-9(MMP-9)적표체화혈뇌병장적변화규률급MMP-9억제제SB-3CT적작용.방법 장건강Sprague-Dawley(SD)웅성대서120지수궤분위가수술대조조、복소대조조화복소치료조,실험지점재중산대학북교구동물실험중심.동물모형채용기관협폐질식법,자주순배회복정의위회복실상성심률,평균동맥압≥60mmHg병차유지5 min이상.가수술대조조부진행마취화기관삽관,복소치료조우자주순배회복후립즉복강내주사SB-3CT 25mg/kg.복소대조조우자주순배회복후불주사SB-3CT.재즉각급3,9,24 h화48 h시간점분5개시간점처사대서후,취양,측정뇌조직MMP-9단백적표체화검측남조직MMP-9 mRNA,관찰뇌함수량화이문사람함량적변화,사용전경관찰뇌조직적초미결구.통계분석채용방차분석법.결과 가수술대조조뇌조직MMP-9표체、MMP-9 mRNA、뇌함수량화이문사람함량재각시간점균무명현변화,p 치분별위1.0000,0.6831,0.7124화0.9975.복소대조조심폐복소후상술지표균명현변화재24 h도체고봉,P 치분별위0.0264,0.0163,0.0000화0.0412,여가수술조비교유통계학의의.복소치료조심폐복소후상술지표변화여복소대조조상사,단변화정도교복소대조조경,P 치분별위0.0392,O.0373,0.O004화O.0180.뇌조직손상정황통과전경관찰득도증실.결론 대서심폐복소후뇌MMP-9,MMP-9 mRNA、뇌함수량화이문사람함량명현승고,혈뇌병장수도파배;전경관찰증실뇌조직손상명현;저사변화재심폐복소후24 h시점체고봉.응용특이성MMP-9억제제SB-3CT가현감소MMP-9적표체,감경뇌수종,대심폐복소후뇌결혈-재관주손상유명현보호작용.
Objective To explore the changes of matrix metalloproteinase-9 and blood brain barrier in cardiopulmonary resuscitation rats and effects of MMP-9 inhibitor on them.Method One hundred and twenty Sprague-Dawley(SD) rats were randomly divided into 3 groups:the sham-operated group,the resuscitation with treatment group and the resuseimfion without treatment group as control.The experiment was made in the animal experiment center of Sun Yat-sen University in Gtlangzhou.The rat eardiopulmonary resuscitation model was made by clipping trachea until asphyxia,and the restoration of spontaneous circulation(ROSC)Was defined by restoration of superventricular rhythm and mean artery pressure (MAP)≥60 mmHg for more than 5 min utes.The rats of sham-operated group were anesahetized only and endotracheal intubation WaS performed.In the resuscitation with treaUnent group ss-3cr(25,ng/ks body weight)Was given intraperitoneally after ROSC.The rats were sacrificed and samples of the brain tissue were taken inmaediately and 3 h,9 h,24 h and 48 h later.After that,the expression of MMP-9 and MMP-9 mRNA in brain tissue were detected.Water oontent and Evans blue in brain tissue Were observed.The uhmmicrostructure of brain tissue was observed under electron microscope.Analysis ofvariance wilE, done with Spssll.0 software.Results 11le expressions of MMP.9 and MMP-9m RNA ofbraintissueiUthe shanloperated group didn't show significant changees in all specimens taken at different intervals and neither the water content and tvans blue did.The Pvalue were 1.0000,0.6831,0.7124 and 0.99r75,respectively.There was no u1.tramicrostruclure change in the sham-operated group.The expressions of MMP_9 and MMP-9 mRNA in the resuscitation control group obviously increased after eardiopulmonary resuscitation,80 did the water content and Evans blue content.Compared with sham-operated group,the P value were 0.0264,0.0163,0.0000 and 0.0412,respee.tively.111e elge of ultmmicrostmeture in the resuscitation control group at different intervals were obvious.The changes of obove biomarkers in the resuscitation treatment group Was siroilar to but less in magnitude than those in the resuscitation control group.The P valHe were 0.0392,0.0373,0.O004 and 0.0180,respectively.Conclusions The expressions of MMP-9 and MMP.9 mRNA obviously increases in the cerebral ischemia model of rats with CPR,and reaches peak at 24 h.Water content and Evans blue content in brain risque obviously increases in the cerebral ischemia model of rats with CPR.BBB iS destroyed.and the peak time iS at 24 h.The injury of ultrami.crostructure of brain tissue under electron microscope iS obvious,and the peak time is at 24 h.The SB-3CT.specif-iC inhibitor of MMP-9 could decrease the expression of MMP-9 and decrease cerebral edema in the cerebral is.chemia modeJ of rats with CPR,and the protection from cerebral isehemia/reperfusion injury after CPR is obvious.
