血管生成素样蛋白 2（ANGPTL2）对大鼠局灶性脑缺血 /再灌注损伤的炎症保护机制研究

目的　探讨血管生成素样蛋白2（Angiogenin-like protein 2,ANGPTL2）在大鼠缺血/ 再灌注后脑损伤过程中 的炎症保护机制。方法　选择健康雄性Wister 大鼠60 只,建立大鼠局灶性脑缺血/ 再灌注损伤模型,随机分为假手术 组和ANGPTL2 组。建模后6 , 12 , 24 , 48 和72 h 后,采用实时定量PCR（real-time quantitative PCR）以及苏木精- 伊 红染色法（hematoxylin-eosin,HE）检测每组大鼠体内ANGPTL2 的表达水平。在建模48 h 后分别记录每组大鼠的神经 功能评分,检测其脑组织含水量、血脑屏障（blood brain barrier,BBB）通透性以及脑梗死体积。采用酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA) 在建模前(T0)、建模后2 h(T1)、建模后6 h(T2)、建模后12 h(T3) 和建模后24 h(T4) 分别检测大鼠血清中S-100β、肿瘤坏死因子-α（tumor necrosis factor α,TNF-α）和白细胞介素-1（interleukin-1, IL-1）的表达水平。结果　在缺血30 和90 min 中的ANGPTL2 组再灌注6,12,24,48 和72 h 的ANGPTL2 mRNA 表 达水平均高于假手术组。ANGPTL2 组大鼠的脑组织含水量、伊水思蓝含量和脑梗死体积均显著低于假手术组,而神经 功能评分高于假手术组,差异均有统计学意义（t =2.431~6.058, 均P ＜ 0.05）。相较于T0,大鼠在T1 时的S-100B 显著 增加,随着建模时间的延长,S-100β 水平逐渐降低,并且与T0 的差异均有统计学意义（t =2.346~3.649, 均P ＜ 0.05）。 相较于T0,ANGPTL2 组大鼠在T1,T2,T3,T4 时血清中的TNF-α 和IL-1 水平均显著升高,且差异具有统计学意义 （t =5.036~9.775, 均P ＜ 0.05）。结论　ANGPTL2 可以降低大鼠局灶性脑缺血/ 再灌注后血脑屏障的通透性,并减轻脑 血管炎症反应,对脑缺血/ 再灌注损伤具有保护作用。     

Elevated serum levels of S-100beta protein and neuron-specific enolase are associated with brain injury in patients with severe sepsis and septic shock

OBJECTIVE: We investigated whether serum levels of neuron-specific enolase (NSE) and S-100beta protein could be used to evaluate cerebral injury and to predict outcome in severe sepsis and severe septic shock. DESIGN: Prospective study. SETTING: University hospital. PATIENTS AND MEASUREMENTS: In 170 consecutively enrolled patients with severe sepsis and septic shock, serum S-100beta and NSE were measured daily during four consecutive days after intensive care unit admission. Admission Glasgow Coma Scale before sedation and daily Sequential Organ Failure Assessment scores were recorded in all patients. Acute encephalopathy was defined as either a state of agitation, confusion, irritability, and convulsions (type A) or characterized by somnolence, stupor, and coma (type B) and persistently observed during 72 hrs after withdrawing sedation. When clinically indicated, contrast computed tomography or magnetic resonance imaging were performed to evaluate brain injury. MAIN RESULTS: S-100beta and NSE increased in, respectively, 72 (42%) and 90 (53%) patients. High biomarker levels were associated with the maximum Sequential Organ Failure Assessment scores (p = .001), and the highest values were found in patients who died early, within 4 days of inclusion (p = .005). Low consciousness encephalopathy type B was more frequently observed in patients with elevated S-100beta (p = .004). S-100beta levels of >or=4 microg/L were associated with severe brain ischemia or hemorrhage, and values of <2 microg/L were found in patients with diffuse cerebral embolic infarction lesions. High S-100beta levels were associated with higher intensive care unit mortality (p = .04) and represented the strongest independent predictor of intensive care unit survival, whereas NSE and the Glasgow Coma Scale failed to predict fatal outcome. CONCLUSIONS: S-100beta and NSE are frequently increased and associated with brain injury in patients with severe sepsis and septic shock. S-100beta levels more closely reflected severe encephalopathy and type of brain lesions than NSE and the Glasgow Coma Scale.     

脑梗死患者血清和脑脊液S-100B蛋白含量的变化

目的：通过测定脑梗死患者急性期，恢复期血清和脑脊液S-100B蛋白含量动态变化，探讨其在脑梗死发病中的临床意义。方法：60例脑梗死住院患者（梗死组），将发病72h和7、21d的脑脊液及静脉血测定血清和脑脊液中S-100B蛋白含量，并分别与正常组比较。结果：梗死组患者发病72h和7d时血清和脑脊液S-100B蛋白显著高于21d患者和正常组（P〈0．01）；血清和脑脊液S-100B蛋白含量与梗死体积及神经功能缺损程度均呈正相关（P〈0．01）；脑脊液S-100B蛋白含量与年龄正相关，血清S-100B蛋白含量与年龄无关。结论：血清或脑脊液中的S-100B蛋白浓度可反映神经胶质细胞的损害程度。对判断病情程度。评估预后和调整治疗方案有重要意义。     

急性脑卒中患者血清S-100B蛋白的检测

目的 讨论急性脑卒中患者血清S-100B蛋白的表达规律及临床意义.方法 用ELISA法对70例急性脑卒中患者发病24 h内的血清S-100B蛋白含量及健康对照组40例进行检测.结果 急性脑卒中缺血性和出血性患者血清S-100B蛋白含量均显著高于健康对照组(P＜0.01);急性脑卒中缺血性和出血性患者血清S-100B蛋白含量比较,差异无统计学意义(P＞0.05);脑卒中含量高低与病情严重程度有密切关系.结论 血清S-100B蛋白的含量可作为急性脑卒中病情监测的指标.     

Early elevation of S-100B protein in blood after cardiac surgery is not a predictor of ischemic cerebral injury

BACKGROUND: We hypothesized that early changes in S-100B levels after cardiac surgery are nonspecific and mostly reflect damage to tissues outside the brain rather than ischemic brain damage. METHODS: We measured serum levels of S-100B at several times perioperatively in 21 patients undergoing cardiac surgery. In addition, we measured levels of neuron specific enolase (NSE), glial fibrillary acidic protein (GFAP), creatine kinase (CK), the cardiac isoenzyme of CK (CK-MB), and myoglobin (MB) in these patients. RESULTS: Early increases in serum S-100B concentration were significantly (p<0.01) correlated with increases in markers of tissue injury outside the brain: S-100B/CK: r(2)=0.69; S-100B/CK-MB: r(2)=0.64; S-100B/myoglobin: r(2)=0.60; S-100B/NSE: r(2)=0.51; CK/NSE: r(2)=0.60; CK-MB/NSE: r(2)=0.59; and myoglobin/NSE: r(2)=0.54. CONCLUSIONS: Our findings indicate that increases in S-100B in the early phase after cardiac surgery are not due to release of S-100B from brain alone but also from tissue outside the brain.     

70例急性脑梗死患者血清OX—LDL及S—100B蛋白检测分析

目的讨论急性脑梗死患者血清OX-LDL、S-100B蛋白的表达规律及临床意义。方法用ELISA法检测70例急性脑梗死患者发病24h内及40例正常时照组血清OX-LDL、S-100B蛋白含量。结果急性脑梗死患者血清0X—LDL、S-100B蛋白含量均显著高于正常对照组（P〈0．01）,它们分别为（615．9±197．6）μg／L、（0．884±0．594）μg／L;正常对照组为（158．6±68．4）μg／L、（0．065±0．02）μg／L。急性脑梗死患者血清OX-LDL、S-100B蛋白含量呈正相关（r=0．536,P〈0．01）,且含量高低与病情严重程度有密切关系。结论血清OX-LDL、S-100B蛋白的含量可作为急性脑梗死病情监测的指标。     

Impairment of blood-brain barrier integrity during carotid surgery as assessed by serum S-100B protein concentrations.

During carotid endarterectomy (CEA) the internal carotid artery is cross-clamped for a period of several minutes. This maneuver may cause cerebral hypoperfusion and/or impairment of the blood-brain barrier (BBB) even in cases where clinical signs are absent. The aim of the present study was to examine whether such alterations could be detected by monitoring the cerebral marker S-100B protein concentrations during and after CEA in the serum. Twenty-five consecutive patients (17 M/8 F, mean age: 64.2 years, range 47-79 years) undergoing elective CEA at our department were studied. All of these patients were without perioperative neurological deficit. Intraoperative samples were collected from internal jugular and peripheral venous blood: 1) before carotid cross-clamping; 2) immediately before declamping; 3) after clamp release. Postoperative samples were taken from peripheral blood at 6 and 24 h, respectively. S-100B was assayed in sera using an immunoluminometric technique. During carotid cross-clamping, S-100B protein concentrations in the ipsilateral jugular serum significantly (p < 0.02) increased to pre-clamp values. After declamping, however, S-100B returned to the baseline level. No differences were seen between the responses of hypertensive and normotensive patients. There was no correlation between carotid occlusion time and S-100B protein concentrations. In the peripheral venous serum no significant changes in S-100B concentrations were detected during or after CEA. We presume that the elevation of S-100B protein concentration during CEA in patients with no neurological deficits indicates the transient opening of the BBB elicited by carotid cross-clamping.     

缺血性脑卒中患者血清S-100β蛋白变化的临床意义探讨

目的通过测定急性缺血性脑卒中患者血清S-100β蛋白的变化,探讨其与梗死灶大小、神经学状态和神经学预后间的关系。方法采用双抗体夹心酶联免疫吸附试验（ELISA）检测急性缺血性脑卒中患者发病后48h内、第5天、第7天和第14天血清S-100β水平。所有患者于相应时间用美国国立卫生研究院卒中量表（NIHSS）进行神经学状态评估,并于出院时评估神经学功能（BI）。结果患者组各时间点S-100β水平与对照组差异均无统计学意义。S-100β于所有时间点,较大、中等和较小梗死灶组及对照组差异有统计学意义（P〈0．05）,且与相应NIHSS和出院时BI均有非常明显的相关性（P=0．000）。较大梗死灶组血清S-100β水平较高。结论S-100β水平在缺血性脑卒中患者中明显升高,有望成为缺血性脑卒中早期评估、揭示疾病严重程度和评估预后的指标。     

胆红素脑病仔鼠脑组织S-100的mRNA及其蛋白变化研究

目的：观察胆红素脑病仔鼠脑组织S-100蛋白（S-100）的mRNA及其蛋白变化．探讨其对胆红素脑病的诊断价值和其分子生物学机制。方法：采用新生7d龄清洁级Wistar大鼠腹腔注射胆红索200mg／kg制备胆红素脑病模型。应用逆转录-聚合酶链反应（RT—PCR）技术动态观察胆红素脑病仔鼠不同时间点脑组织S-100 mRNA表达变化；应用免疫组织化学方法动态观察不同时间点脑组织S-100蛋白表达变化。结果：实验组脑组织S-100 mRNA表达12h明显升高．48h达峰值．至96h与对照组差异无显著性意义：造模后12h海马区脑组织S-100阳性表达明碌升高，48h达峰值，至96h与对照组无显著性差异；皮质区6h明显升高。48h达峰值，至96h与对照组差异无显著性意义；丘脑区6h明显升高，72h下降，至96h与对照组无显著性差异；苍白球区6h明显升高，48h达峰值，72h下降，至96h与对照组比较仍有显著性差异。结论：S-100mRNA的变化同S-100蛋白的变化趋势一致，是判定胆红素脑病的可靠神经生化指标。     

δ阿片受体激动剂DADLE对全脑缺血-再灌注大鼠血清S-100B蛋白的影响

目的 通过比较血清S-100B蛋白水平来观察δ阿片受体激动剂DADLE对大鼠全脑缺血-再灌注损伤的影响,从而探讨DADLE在脑复苏中的神经保护作用.方法 用二血管阻断加低血压法制作大鼠全脑缺血-再灌注模型.50只SD大鼠随机分为五组,每组各10只;假手术组:不制模不干预;模型组:单纯制作全脑缺血-再灌注模型;DADLE预处理组:在缺血前给予DADLE;DADLE缺血后处理组:在缺血后给予DADLE;DADLE再灌注期处理组:在再灌注早期给予DADLE.实验结束后分别取血,用酶联免疫检测法(ELISA)测定大鼠血清S-100B蛋白水平.数据用均数4±标准差((x)±s)表示,统计分析采用单因素方差分析,两两组间均数之间的比较采用SNK法,以P<0.05为差异具有统汁学意义.结果 假手术组的血清S-100B蛋白水平为(475.56±41.93)pg/ml,模型组和DADLE处理各组的山清S-100B蛋白水平均比假手术组高(P<0.05),DADLE处理各组的血清S-100B蛋白水平均比模型组低(P<0.05),DADIE处理各组间的血清S-100B蛋白水平差异无统计学意义(P>0.05).结论 δ阿片受体激动剂DADLE对大鼠全脑缺血-再灌注损伤有保护作作用.     

大鼠急性脑缺血再灌注后血脑屏障的变化

目的研究大鼠急性脑缺血再灌注的血脑屏障变化以及MRI表现.方法 44只SD大鼠随机分为4组,采用大鼠线栓法建立急性脑缺血再灌注模型,A组、C组脑缺血2 h, B组、D组缺血6 h,A组、B组中每组10只分别于灌注前、再灌注后2 h和24 h行MRI检查,4只大鼠行组织学检查.C组、D组每组12只,分别于再灌注后2 h和24 h观察脑组织中伊文氏蓝染色情况并测量其含量. 结果 A、B两组再灌注前均无强化表现,再灌注后2 hA组10例中4例出现斑片状强化,B组10例均出现大片明显强化(P＜0.05),B组中3例再灌注24 h T1WI出现高信号,相应大体标本断面可见出血灶,组织学观察显示B组脑组织损伤较A组严重.C组中8例可见右尾壳核斑片状蓝染区,而D组12例右尾壳核及额顶叶皮质区均见蓝染,测量两组右侧大脑半球伊文氏蓝含量与对侧相比均有显著性差异(P＜0.05),两组之间右侧大脑半球伊文氏蓝含量相比有显著性差异(P＜0.01),C组中再灌注2 h与再灌注24 h伊文氏蓝含量相比较有显著性差异(P＜0.05),D组中再灌注2 h与再灌注24 h伊文氏蓝含量无差异(P＞0.05).结论缺血再灌注时血脑屏障的损伤随着缺血时间的延长而加重,MRI增强扫描作为一个无创性、可重复性检查方法,有助于评价急性脑缺血再灌注后血脑屏障的状况.     

葛根素预处理对大鼠脑缺血再灌注损伤后脑组织含水量的影响

目的 观察葛根素预处理对大鼠局灶性脑缺血再灌注损伤后脑组织含水量的影响,为葛根素的临床应用提供依据.方法 制作大脑中动脉缺血2 h后再灌注损伤模型.将SD大鼠72只随机分为假手术组(S组)﹑致死性缺血再灌注组(IR组)、葛根素预处理组(P组)各24只,各组大鼠分别按脑缺血再灌注后24 h、72 h、120 h处死动物时间的不同,每组再分为3个亚组,每个亚组8只大鼠.采用干湿重法测定脑组织含水量,观察预处理对缺血2 h再灌注损伤24 h、72 h、120 h脑组织含水量的影响.结果 IR组及P组实验术后24 h、72 h、120 h各亚组脑组织含水量均显著高于S组各亚组(P 均＜0.01);但P组各亚组脑组织含水量均低于同期IR组各亚组(P＜0.05).结论 葛根素预处理能显著减少大鼠局灶性脑缺血后脑组织含水量,对脑组织具有保护作用.     

Serum S-100B protein monitoring in patients with severe traumatic brain injury

Objective S-100B protein is a promising marker of injury severity and outcome after head injury. We examined the relationship between serum S-100B concentrations and injury severity, clinical course, survival, and treatment efficacy after severe traumatic brain injury (TBI). Design and setting Prospective observational study in a neurosurgical intensive care unit. Patients and participants 102 adult patients with severe TBI, admitted between June 2001 and November 2003 (30 months). Interventions Serum S-100B levels were measured by immunoluminometric technique on admission and every 24 h thereafter for a maximum of 7 days. Measurements and results Initial S-100B levels were significantly related to pupillary status, computed tomography severity1, and 1-month survival. Cox's proportional hazard regression analysis showed that initial S-100B was an independent predictor of 1-month survival, in the presence of dilated pupils, and with increased age. Subjects with initial levels above 1 μg/l had a nearly threefold increased probability of death within 1 month. Serum S-100B alteration indicated neurological improvement or deterioration. Finally, surgical treatment reduced S-100B levels. Conclusions Serum S-100B protein reflects injury severity and improves prediction of outcome after severe TBI. S-100B may also have a role in assessing the efficacy of treatment after severe TBI.     

基质金属蛋白酶-9抑制剂SB-3CT对心肺复苏大鼠血脑屏障作用的研究

目的 观察心肺复苏(CPR)早期大鼠脑组织基质金属蛋白酶-9(MMP-9)和血脑屏障的变化及MMP-9抑制剂SB-3CT对其的作用.方法 将动物随机分为假手术组、复苏对照组和复苏治疗组,夹闭气管插管致大鼠心搏骤停,1 min后进行CPR,复苏治疗组于自主循环恢复(ROSC)后立即腹腔注射MMP-9抑制剂SB-3CT 25 mg/kg.各组于ROSC 0、3、9、24和48 h分别处死8只大鼠后,观察血脑屏障变化;测定脑组织MMP-9的蛋白和mRNA表达;电镜下观察超微结构改变.结果 假手术组各时间点脑含水量、伊文思蓝含量、脑组织MMP-9蛋白及mRNA表达和电镜观察均无明显变化.复苏对照组各指标于3 h起明显升高,24 h达高峰,与假手术组比较差异均有统计学意义;血脑屏障明显改变.复苏治疗组ROSC后上述指标变化趋势与复苏对照组相似,但损伤程度较复苏对照组轻(P<0.05或P<0.01).结论 MMP-9抑制剂SB-3CT可明显减少MMP-9表达,减轻血脑屏障损伤,减轻脑水肿,对CPR后脑缺血/再灌注损伤有明显保护作用.     

基质金属蛋白酶-9抑制剂SB-3CT对心肺复苏大鼠血脑屏障作用的研究

目的 观察心肺复苏(CPR)早期大鼠脑组织基质金属蛋白酶-9(MMP-9)和血脑屏障的变化及MMP-9抑制剂SB-3CT对其的作用.方法 将动物随机分为假手术组、复苏对照组和复苏治疗组,夹闭气管插管致大鼠心搏骤停,1 min后进行CPR,复苏治疗组于自主循环恢复(ROSC)后立即腹腔注射MMP-9抑制剂SB-3CT 25 mg/kg.各组于ROSC 0、3、9、24和48 h分别处死8只大鼠后,观察血脑屏障变化;测定脑组织MMP-9的蛋白和mRNA表达;电镜下观察超微结构改变.结果 假手术组各时间点脑含水量、伊文思蓝含量、脑组织MMP-9蛋白及mRNA表达和电镜观察均无明显变化.复苏对照组各指标于3 h起明显升高,24 h达高峰,与假手术组比较差异均有统计学意义;血脑屏障明显改变.复苏治疗组ROSC后上述指标变化趋势与复苏对照组相似,但损伤程度较复苏对照组轻(P<0.05或P<0.01).结论 MMP-9抑制剂SB-3CT可明显减少MMP-9表达,减轻血脑屏障损伤,减轻脑水肿,对CPR后脑缺血/再灌注损伤有明显保护作用.     

基质金属蛋白酶-9抑制剂SB-3CT对心肺复苏大鼠血脑屏障作用的研究

目的 观察心肺复苏(CPR)早期大鼠脑组织基质金属蛋白酶-9(MMP-9)和血脑屏障的变化及MMP-9抑制剂SB-3CT对其的作用.方法 将动物随机分为假手术组、复苏对照组和复苏治疗组,夹闭气管插管致大鼠心搏骤停,1 min后进行CPR,复苏治疗组于自主循环恢复(ROSC)后立即腹腔注射MMP-9抑制剂SB-3CT 25 mg/kg.各组于ROSC 0、3、9、24和48 h分别处死8只大鼠后,观察血脑屏障变化;测定脑组织MMP-9的蛋白和mRNA表达;电镜下观察超微结构改变.结果 假手术组各时间点脑含水量、伊文思蓝含量、脑组织MMP-9蛋白及mRNA表达和电镜观察均无明显变化.复苏对照组各指标于3 h起明显升高,24 h达高峰,与假手术组比较差异均有统计学意义;血脑屏障明显改变.复苏治疗组ROSC后上述指标变化趋势与复苏对照组相似,但损伤程度较复苏对照组轻(P<0.05或P<0.01).结论 MMP-9抑制剂SB-3CT可明显减少MMP-9表达,减轻血脑屏障损伤,减轻脑水肿,对CPR后脑缺血/再灌注损伤有明显保护作用.     

基质金属蛋白酶-9抑制剂SB-3CT对心肺复苏大鼠血脑屏障作用的研究

目的 观察心肺复苏(CPR)早期大鼠脑组织基质金属蛋白酶-9(MMP-9)和血脑屏障的变化及MMP-9抑制剂SB-3CT对其的作用.方法 将动物随机分为假手术组、复苏对照组和复苏治疗组,夹闭气管插管致大鼠心搏骤停,1 min后进行CPR,复苏治疗组于自主循环恢复(ROSC)后立即腹腔注射MMP-9抑制剂SB-3CT 25 mg/kg.各组于ROSC 0、3、9、24和48 h分别处死8只大鼠后,观察血脑屏障变化;测定脑组织MMP-9的蛋白和mRNA表达;电镜下观察超微结构改变.结果 假手术组各时间点脑含水量、伊文思蓝含量、脑组织MMP-9蛋白及mRNA表达和电镜观察均无明显变化.复苏对照组各指标于3 h起明显升高,24 h达高峰,与假手术组比较差异均有统计学意义;血脑屏障明显改变.复苏治疗组ROSC后上述指标变化趋势与复苏对照组相似,但损伤程度较复苏对照组轻(P<0.05或P<0.01).结论 MMP-9抑制剂SB-3CT可明显减少MMP-9表达,减轻血脑屏障损伤,减轻脑水肿,对CPR后脑缺血/再灌注损伤有明显保护作用.     

基质金属蛋白酶-9抑制剂SB-3CT对心肺复苏大鼠血脑屏障作用的研究

目的 观察心肺复苏(CPR)早期大鼠脑组织基质金属蛋白酶-9(MMP-9)和血脑屏障的变化及MMP-9抑制剂SB-3CT对其的作用.方法 将动物随机分为假手术组、复苏对照组和复苏治疗组,夹闭气管插管致大鼠心搏骤停,1 min后进行CPR,复苏治疗组于自主循环恢复(ROSC)后立即腹腔注射MMP-9抑制剂SB-3CT 25 mg/kg.各组于ROSC 0、3、9、24和48 h分别处死8只大鼠后,观察血脑屏障变化;测定脑组织MMP-9的蛋白和mRNA表达;电镜下观察超微结构改变.结果 假手术组各时间点脑含水量、伊文思蓝含量、脑组织MMP-9蛋白及mRNA表达和电镜观察均无明显变化.复苏对照组各指标于3 h起明显升高,24 h达高峰,与假手术组比较差异均有统计学意义;血脑屏障明显改变.复苏治疗组ROSC后上述指标变化趋势与复苏对照组相似,但损伤程度较复苏对照组轻(P<0.05或P<0.01).结论 MMP-9抑制剂SB-3CT可明显减少MMP-9表达,减轻血脑屏障损伤,减轻脑水肿,对CPR后脑缺血/再灌注损伤有明显保护作用.     

基质金属蛋白酶-9抑制剂SB-3CT对心肺复苏大鼠血脑屏障作用的研究

目的 观察心肺复苏(CPR)早期大鼠脑组织基质金属蛋白酶-9(MMP-9)和血脑屏障的变化及MMP-9抑制剂SB-3CT对其的作用.方法 将动物随机分为假手术组、复苏对照组和复苏治疗组,夹闭气管插管致大鼠心搏骤停,1 min后进行CPR,复苏治疗组于自主循环恢复(ROSC)后立即腹腔注射MMP-9抑制剂SB-3CT 25 mg/kg.各组于ROSC 0、3、9、24和48 h分别处死8只大鼠后,观察血脑屏障变化;测定脑组织MMP-9的蛋白和mRNA表达;电镜下观察超微结构改变.结果 假手术组各时间点脑含水量、伊文思蓝含量、脑组织MMP-9蛋白及mRNA表达和电镜观察均无明显变化.复苏对照组各指标于3 h起明显升高,24 h达高峰,与假手术组比较差异均有统计学意义;血脑屏障明显改变.复苏治疗组ROSC后上述指标变化趋势与复苏对照组相似,但损伤程度较复苏对照组轻(P<0.05或P<0.01).结论 MMP-9抑制剂SB-3CT可明显减少MMP-9表达,减轻血脑屏障损伤,减轻脑水肿,对CPR后脑缺血/再灌注损伤有明显保护作用.     

基质金属蛋白酶-9抑制剂SB-3CT对心肺复苏大鼠血脑屏障作用的研究

目的 观察心肺复苏(CPR)早期大鼠脑组织基质金属蛋白酶-9(MMP-9)和血脑屏障的变化及MMP-9抑制剂SB-3CT对其的作用.方法 将动物随机分为假手术组、复苏对照组和复苏治疗组,夹闭气管插管致大鼠心搏骤停,1 min后进行CPR,复苏治疗组于自主循环恢复(ROSC)后立即腹腔注射MMP-9抑制剂SB-3CT 25 mg/kg.各组于ROSC 0、3、9、24和48 h分别处死8只大鼠后,观察血脑屏障变化;测定脑组织MMP-9的蛋白和mRNA表达;电镜下观察超微结构改变.结果 假手术组各时间点脑含水量、伊文思蓝含量、脑组织MMP-9蛋白及mRNA表达和电镜观察均无明显变化.复苏对照组各指标于3 h起明显升高,24 h达高峰,与假手术组比较差异均有统计学意义;血脑屏障明显改变.复苏治疗组ROSC后上述指标变化趋势与复苏对照组相似,但损伤程度较复苏对照组轻(P<0.05或P<0.01).结论 MMP-9抑制剂SB-3CT可明显减少MMP-9表达,减轻血脑屏障损伤,减轻脑水肿,对CPR后脑缺血/再灌注损伤有明显保护作用.