人脑出血后血肿周围组织HO-1、GFAP和cyclinD1的表达研究

目的探讨脑出血后血肿周围组织血红素氧合酶-1(HO-1)、胶质纤维酸性蛋白(GFAP)和细胞周期蛋白D1(cvclinD1)表达规律,及其与神经修复之间的关系。方法 HE染色观察脑出血后神经元和星形胶质细胞形态变化,免疫组织化学染色检测脑出血后不同时间点血肿周围组织H0-1、GFAP和cycIinD1表达水平。结果脑出血后2h星形胶质细胞胞质内即开始表达HO-1[(5.30±1.00)个/高倍视野]、GFAP[(22.60±1.40)个/高倍视野]和cvclinD1[(11.50±1.20)个/高倍视野],达峰值水平后逐渐下降,脑出血后不同时间点表达水平均高于健侧正常脑组织,且差异具有统计学意义(均P=0.000)。结论人脑出血后血肿周围组织HO-1、GFAP和cvclinD1表达变化呈"抛物线"样,HO-1和cvclinD1共同参与了脑出血后星形胶质细胞的增生与活化,以及脑出血后的继发性损伤和修复。     

脑出血患者血肿周围脑组织水通道蛋白-4的表达变化

目的：探讨脑出血血肿周围脑组织水通道蛋白-4（AQP4）的表达规律及其与脑水肿形成的关系。方法：32例行颅内血肿清除术患者，按发病至手术时间不同分为〈6h、6～24h、24～72h和〉72h组。取术中获得的脑组织做病理标本，检测AQP4的表达变化，并观察其组织病理及超微结构变化。结果：〈6h组脑组织轻微水肿，AQP4表达呈弱阳性，6h后水肿逐渐加重，AQP4表达开始增强，至24～72h达高峰。此后，AQP4表达下降，水肿减轻。结论：脑出血后AQP4表达呈动态变化与脑组织水肿程度一致，提示AQP4在脑出血患者脑水肿的发生、发展中起着重要作用。     

人脑出血后血肿周围组织HO-1、GFAP和cyclinD1的表达研究

目的探讨脑出血后血肿周围组织血红素氧合酶-1（HO-1）、胶质纤维酸性蛋白（GFAP）和细胞周期蛋白D1（cvclinD1）表达规律,及其与神经修复之间的关系。方法HE染色观察脑出血后神经元和星形胶质细胞形态变化,免疫组织化学染色检测脑出血后不同时间点血肿周固组织HO-1、GFAP和cvclinD1表达水平。结果脑出血后2h星形胶质细胞胞质内即开始表达HO-1[（5．30±1．00、）个,高倍视野]、GFAP[（22．60±1．40）个／高倍视野]和cyclinD1[（11．50±1．20）个,高倍视野],达峰值水平后逐渐下降,脑出血后不同时间点表达水平均高于健侧正常脑组织．且差异具有统计学意义（均P=0.000）。结论人脑出血后血肿周围组织HO-1、GFAP和cvclinD1表达变化呈“抛物线”样,HO-1和evclinD1共同参与了脑出血后星形胶质细胞的增生与活化,以及脑出血后的继发性损伤和修复。     

高血压性脑出血血肿周围脑组织细胞间粘附分子-1的表达

目的探讨急性高血压性脑出血患者细胞间粘附分子-1(ICAM-1)在血肿周围脑组织和正常脑组织中的表达及其意义。方法选择30例行开颅手术治疗的急性高血压性脑出血患者,采用免疫组化技术检测ICAM-1在血肿周围脑组织及正常脑组织中的表达。结果实验组血肿周围脑组织可见ICAM-1的表达水平上调,其表达水平明显高于正常脑组织的表达水平(P<0.01)。神经元和血管内皮细胞共同表达ICAM-1,且神经元表达较明显。结论ICAM-1在人类高血压性脑出血血肿周围脑组织的表达水平上调,其表达上调可能参与了血肿周围脑组织的白细胞浸润,最终引发炎性反应和继发性脑损伤。     

脑出血血肿周围脑组织细胞凋亡与细胞色素C表达的关系

目的 研究脑出血(ICH)患者血肿周围脑组织细胞凋亡与细胞色素C(Cyt-C)表达的关系.方法 选择不同时段行血肿清除术的ICH患者32例,选取手术过程中获得的血肿周围脑组织作为标本,采用TUNEL染色及免疫组织化学技术检测凋亡细胞和Cyt-C表达的变化.结果 ICH超早期组(＜8h)可见明显的TUNEL阳性细胞和Cyt-C阳性细胞;早期组(8～48h)二者均达到高峰;延期组(＞48h)TUNEL阳性细胞仍维持较高表达,而Cyt-C阳性细胞计数开始下降.凋亡细胞与Cyt-C表达呈正相关(r=0.87,P＜0.01).结论 ICH患者血肿周围脑组织中存在细胞凋亡,Cyt-C表达是细胞凋亡过程中的一个关键事件.     

Diffusion-perfusion MR evaluation of perihematomal injury in hyperacute intracerebral hemorrhage.

BACKGROUND: It has been suggested that a zone of perihematomal ischemia analogous to an ischemic penumbra exists in patients with primary intracerebral hemorrhage (ICH). Diffusion-perfusion MRI provides a novel means of assessing injury in perihematomal regions in patients with ICH. OBJECTIVE: To characterize diffusion-perfusion MRI changes in the perihematomal region in patients with hyperacute intracerebral hemorrhage. METHOD: Twelve patients presenting with hyperacute, primary ICH undergoing CT scanning and diffusion-perfusion MRI within 6 hours of symptom onset were reviewed. An automated thresholding technique was used to identify decreased apparent diffusion coefficient (ADC) values in the perihematomal regions. Perfusion maps were examined for regions of relative hypo- or hyperperfusion. RESULTS: Median baseline NIH Stroke Scale score was 17 (range, 6 to 28). Median hematoma volume was 13.3 mL (range, 3.0 to 74.8 mL). MRI detected the hematoma in all patients on echo-planar susceptibility-weighted imaging and in all seven patients imaged with gradient echo sequences. In six patients who underwent perfusion imaging, no focal defects were visualized on perfusion maps in tissues adjacent to the hematoma; however, five of six patients demonstrated diffuse ipsilateral hemispheric hypoperfusion. On diffusion imaging, perihematomal regions of decreased ADC values were identified in three of 12 patients. All three subsequently showed clinical and radiologic deterioration. CONCLUSIONS: A rim of perihematomal decreased ADC values was visualized in the hyperacute period in a subset of patients with ICH. The presence of a rim of decreased ADC outside the hematoma correlated with poor clinical outcome. Although perfusion maps did not demonstrate a focal zone of perihematomal decreased blood flow in any patient, most patients had ipsilateral hemispheric hypoperfusion.     

脑出血患者血清基质金属蛋白酶-9的动态变化研究

目的观察脑出血患者血清基质金属蛋白酶-9(MMP-9)水平的动态变化,并探讨其与水肿体积的关系。方法应用ELISA法对46例脑出血患者血清MMP-9水平进行动态检测,同时与头部CT扫描所显示的血肿周围水肿(PHE)体积作相关性分析。结果脑出血组血清MMP-9水平在发病24小时、3天及7天与对照组比较显著升高(P<0.05),MMP-9含量在不同血肿体积中具有显著性差异(P<0.05),发病3天及7天的MMP-9水平与血肿周围水肿体积呈正相关(P<0.05)。结论脑出血后血清MMP-9表达水平增高,血清MMP-9水平是早期反映脑出血患者血肿周围水肿严重程度和预后的敏感指标。     

实验性出血性脑水肿水通道蛋白4表达与MRI变化的相关性研究

目的 研究大鼠脑出血后血肿周围水通道蛋白4(AQP4)的表达与MRI各项指标变化,探讨AQP4的表达变化规律与出血性脑水肿形成之间的关系. 方法 45只雄性SD大鼠按随机数字表法分为假手术组(n=15)及出血组(n=30),每组又均分为造模后l、2、3、5、7 d组.采用苍白球注射胶原酶造成大鼠脑出血模型,在造模后1、2、3、5、7d行MRI扫描,测量计算血肿周围水肿体积以及水肿区T1WI、T2WI及FLAIR序列的信号强度比,成像后分别于相应时间点处死大鼠,应用免疫组化染色观察AQP4的表达. 结果 各时间点出血组大鼠血肿周围AQP4的表达水平明显高于假手术组,比较差异有统计学意义(P＜0.05),AQP4表达与血肿周围脑水肿体积呈线型正相关关系(r=0.687,P＜0.05),AQP4的表达与血肿周围水肿区T2WI、FLAIR序列的信号强度比呈线型正相关关系(r=0.640,P＜0.05;r=0.662,P＜0.05). 结论 AQP4表达与出血性脑水肿的形成、发展密切相关,AQP4的过度表达可能促进了出血后脑水肿的形成.     

Df—521巴曲酶对大鼠脑出血后脑水肿形成的影响

目的:观察Df-521巴曲酶对大鼠脑出血后脑水肿对血肿周边区脑组织ICAM-1表达的影响。方法:一侧基底节注射自体血制作大鼠脑出血模型,用干湿重法,测定脑组织含水量;用免疫组化法检测血肿周边水肿带ICAM-1的表达情况。结果:大鼠脑出血后,血肿侧脑组织含水量上升,同时水肿区ICAM-1的表达量增加;给予Df-521巴曲酶制剂处理后,血肿侧脑水肿减轻,脑组织ICAM-1的表达有所下降。结论:Df-521巴曲酶能下调脑出血后血肿周边组织ICAM-1的表达并减轻脑水肿的程度。     

水通道蛋白-4在脑出血大鼠脑组织的分布

目的 观察脑出血大鼠水通道蛋白-4(AQP4)在脑组织的分布变化及其在出血性脑水肿中的作用。方法 采用定量胶原酶注人大鼠尾状核建立脑出血模型，应用免疫组化法观察脑出血后不同时间大鼠脑组织AQP4的表达。结果 AQP4阳性细胞主要分布在脑出血血肿周围区和大脑皮质的星形胶质细胞、脑室周围、视上核和室旁核。脑出血后6h起，AQP4表达增强，出血后72h达高峰，出血1周后仍高于正常水平。结论 脑出血后，AQP4在与水代谢密切相关的部位表达明显增强，提示AQP4在出血性脑水肿的形成过程中起重要作用。     

脑出血患者血肿周围水肿形成机制:脑内细胞因子的作用

目的 :探讨脑出血患者脑内炎性细胞因子与血肿周围水肿的形成是否相关。方法 :32例脑出血患者行血肿清除术后 ,留取脑血肿液 ,放免法测定其中肿瘤坏死因子α(TNFα)和白细胞介素 - 6 (IL - 6 )的含量 ,测量术前检查的头 CT上的血肿周围水肿带大小 ,用 SPSS10 0对两者进行相关分析。结果 :脑出血患者脑血肿液中 IL - 6和 TNFα的含量明显高于正常人溶血血清中的含量 (P<0 .0 1) ;脑血肿液中 TNFα和 IL - 6含量与血肿周围水肿带大小呈正相关 (r TNF=0 .5 39,P<0 .0 1;r IL- 6 =0 .5 6 9,P<0 .0 1)。结论 :脑出血患者急性期脑血肿液中 IL - 6和 TNFα含量升高 ;脑内炎性细胞因子可能参与血肿周围水肿的形成     

前列地尔对实验性脑出血大鼠血肿周围组织炎性反应的影响

目的观察前列地尔对实验性脑出血模型大鼠血肿周围组织神经元形态的影响。方法采用立体定向技术于右侧基底节注射自体动脉血制备脑出血大鼠模型。前肢伸置和转身运动测验评价大鼠行为学变化,尼氏染色观察不同处理组大鼠血肿周围组织神经元形态变化,间接免疫荧光染色计数血肿周围组织TNF-α和IL-6表达阳性细胞数目及分布范围。结果脑出血后大鼠行为障碍主要表现为运动感觉损伤和动作不对称,给予前列地尔治疗后其症状与体征明显改善,且于实验第5、7和14天时行为功能恢复程度接近对照组(P<0.05或P<0.01)。组织形态学观察可见,脑出血后血肿周围组织有大量炎性细胞浸润、坏死,呈现"挤压区",其外侧细胞水肿、轮廓不清;经前列地尔治疗后炎性细胞浸润和神经元肿胀不同程度改善,且随着治疗时间的延长脑出血同侧正中裂旁皮质区神经元数目逐渐增加,至治疗结束时接近正常水平(P=0.650)。脑出血后血肿周围组织神经元高表达TNF-α和IL-6,阳性细胞主要分布于血肿周围组织,血肿远隔部位和健侧几乎不表达;经前列地尔治疗后,二者表达水平呈逐渐降低趋势,并于治疗第7(P=0.035,0.023)和14天(P=0.024,0.020)时接近正常水平。结论前列地尔对脑出血模型大鼠神经功能改善的机制,可能与抑制血肿周围组织炎性反应、减少血肿周围组织继发性神经元损害有关。     

脑出血早期应用三七总皂甙治疗的临床观察

目的　观察脑出血早期应用三七总皂甙改善微循环治疗的临床疗效。方法　收集 1998～ 2 0 0 2年在我科住院的 5 19例急性脑出血患者分为治疗组和对照组 ,进行疗效对比。结果　治疗组和对照组的总有效率分别为 85 .3%和 6 0 .7% (P<0 .0 1)。治疗组和对照组死亡率分别为 4 .3%和 10 .1% (P<0 .0 1)。发病第 7天 :治疗组水肿带不明显 ,对照组有轻度的水肿 ;发病第 14天 :治疗组血肿有所吸收 ,周围有轻微低密度区 (水肿 ) ;对照组血肿吸收不明显 ,周围水肿明显 ;发病第 2 8天 :治疗组大部分患者血肿完全吸收 ,水肿带明显缩小 ,有的甚至未见水肿 ;对照组部分患者血肿完全吸收 ,大部分血肿周围水肿明显。结论　三七总皂甙有良好的改善微循环作用 ,能够促进血肿吸收 ,明显抑制脑水肿的发生、发展 ,并且显著缩短水肿带的消失时间 ,对血肿周围缺血区有着重要意义 ,对脑出血急性期有明显疗效。     

水蛭素和重组链激酶联合应用于脑出血血肿腔中的实验研究

目的研究水蛭素和重组链激酶联合应用于脑内出血(ICH)血肿腔中对血肿周围脑组织的影响.方法 72只SD雄性大鼠制成ICH模型,随机分为对照组、重组链激酶组、水蛭素 重组链激酶组(联合组),各组分别在ICH后8 h、16 h、24 h、48 h向血肿腔中注入生理盐水、重组链激酶、或重组链激酶加水蛭素.ICH后72 h处死大鼠,观察脑组织中的含水量、Na 、K 以及血脑屏障通透性的变化.结果在ICH后8 h、16 h、24 h、48 h应用重组链激酶,可引起脑组织含水量增加以及Na 、K 的变化(P<0.05),在ICH后8 h重组链激酶组,脑组织中伊文思蓝(Evans blue,EB)含量明显升高(P<0.05).联合组与重组链激酶组比较脑组织的含水量在8 h、16 h、24 h、48 h明显降低(P<0.05),脑组织中EB含量在8 h、16 h、24 h、48 h也明显降低(P<0.05).结论 ICH血肿腔内单独应用重组链激酶可加重ICH血肿周围脑组织的损伤,联合应用水蛭素不但可防治重组链激酶溶化血块时对脑组织的损伤,而且还可降低血肿本身所释放的毒性物质所引起的脑水肿及血脑屏障的破坏.     

自发性脑出血早期血肿扩大首诊CT分析

探讨首诊头部CT影像对自发性脑出血早期血肿扩大的预测价值。300例发病后6h内入院的自发性脑出血患者,经CT检查显示其中61例(20.33%)发生早期血肿扩大,经单因素和多因素Logistic回归分析显示,早期血肿扩大与首诊CT距发病时间短、血肿密度不均匀、中至重度脑萎缩及血     

前列地尔对实验性脑出血大鼠血肿周围组织炎性反应的影响

目的观察前列地尔对实验性脑出血模型大鼠血肿周围组织神经元形态的影响。方法采用立体定向技术于右侧基底节注射自体动脉血制备脑出血大鼠模型。前肢伸置和转身运动测验评价大鼠行为学变化,尼氏染色观察不同处理组大鼠血肿周围组织神经元形态变化,间接免疫荧光染色计数血肿周围组织TNF-α和IL-6表达阳性细胞数目及分布范围。结果脑出血后大鼠行为障碍主要表现为运动感觉损伤和动作不对称,给予前列地尔治疗后其症状与体征明显改善,且于实验第5、7和14天时行为功能恢复程度接近对照组（P〈0．05或P〈0．01）。组织形态学观察可见,脑出血后血肿周围组织有大量炎性细胞浸润、坏死,呈现“挤压区”,其外侧细胞水肿、轮廓不清;经前列地尔治疗后炎性细胞浸润和神经元肿胀不同程度改善,且随着治疗时间的延长脑出血同侧正中裂旁皮质区神经元数目逐渐增加,至治疗结束时接近正常水平（P=0．650）。脑出血后血肿周围组织神经元高表达TNF-α和IL-6,阳性细胞主要分布于血肿周围组织,血肿远隔部位和健侧几乎不表达;经前列地尔治疗后,二者表达水平呈逐渐降低趋势,并于治疗第7（P=0．035,0．023）和14天（P：0．024,0．020）时接近正常水平。结论前列地尔对脑出血模型大鼠神经功能改善的机制,可能与抑制血肿周围组织炎性反应、减少血肿周围组织继发性神经元损害有关。     

脑出血患者血肿周围组织中NF-κB的病理学观察

目的 探讨脑出血患者脑组织中NF-κB(nuclear factor-kappaB)的表达特征及意义.方法 筛选临床脑出血患者死亡病例21例,按出血时间(发病至死亡时间)分为6组:0～6h、6～12h、12～24h、24～48h、48～72h、72～96h.自出血灶边缘13cm处、海马和大脑皮层及出血灶对侧相应部位的脑组织取材,出血灶对侧设为对照组.采用免疫组织化学染色观察NF-κB在脑组织中的表达.结果 脑出血后6h时出血灶周围即有NF-κB蛋白表达(5.27±0.12),6～12h表达增加(8.52±0.66),24～48h时达高峰(34.47±2.81),72～96h表达减少(19.50±2.69),与对照组比较差异无统计学意义(P>0.05),但与0～6h组比较差异有统计学意义(P<0.05).NF-κB蛋白还表达于两侧海马和大脑皮层.结论 脑出血后脑组织中NF-κB表达增加,对脑水肿的形成可能有一定的促进作用.

Abstract：

Objective To study the expression and significance of NF-κB in human brain after intracerebral hemorrhage. Method 21 human clinical fatal cases with ICH were divided into 6 groups according to different onset time :0 6h,6 12h, 12 24h,24 48h,48 72h and 72 96h group. The brain tissues were removed frome 1 3cm away from the margin of the hemorrhagic lesion, hippocampus and cerebral cortex of the side of hematoma, as well as tissues from the corresponding areas of other side were taken as controls. NF-κB expression was detected by immunohistochemistry. Result There was little expression of NF-κB at 6h after ICH (5.27±0.12). The expression of NF-κB begun to increase at 6～12h (8.52±0.66), reached the peak at 24～48h (34.47±2.81 ), and gradually decreased at 72～96h ( 19.5±2.69). There had no significant difference compared with normal contralateral regions (P > 0. 05 ), but had significant difference compared with 0 -6h group (P < 0.05). There was expression of NF-κB in hippocampus and cortex. Conclusion The increased expression of NF-κB after intracerebral hemorrhage is probably correlated with the brain edema formation in the brain tissues around the hematoma.     

Mild hypothermia effects on matrix metalloproteinase-9 expression in the perihematomal region of rats following experimental intracerebral hemorrhage**☆

BACKGROUND： Matrix metalloproteinase-9 （MMP-9） expression increases with intracerebral hemorrhage, and participates in the pathophysiological processes of secondary brain injury after intracerebral hemorrhage.
OBJECTIVE： To investigate the effects of mild hypothermia on MMP-9 expression and brain edema in the perihematomal region of experimental intracerebral hemorrhage rats.
DESIGN, TIME AND SETTING： The randomized, controlled experiment was performed at the Central Laboratory of Shandong Provincial Hospital between May and September 2007.
MATERIALS： Seventy-two, Wistar, male rats, 12-weeks old, were used for this study. Rabbit anti-MMP-9 primary antibody was purchased from Boster, China.
METHODS： Wistar rats were equally and randomly divided into normothermia and mild hypothermia groups. The two groups each comprised control, 6-hour intracerebral hemorrhage, 24-hour intracerebral hemorrhage, 48-hour intracerebral hemorrhage, 72-hour intracerebral hemorrhage, and l-week intracerebral hemorrhage subgroups, with six rats in each subgroup. Rat models of intracerebral hemorrhage were established by injecting 100 μL of autologous blood into the rat caudate nucleus. Rats in the mild hypothermia group received four hours of local mild hypothermia immediately following the injection. lntracerebral temperature was maintained at （33 ± 0.5） ℃. Subsequently, intracerebral temperature was spontaneously recovered at 25 ℃. Rats in the control subgroup were not injected with autologous blood and received only with intracerebral hemorrhage.
MAIN OUTCOME MEASURES： Brain water content and MMP-9 expression surrounding the hematoma region. RESULTS： MMP-9 expression increased at 6 hours, and brain edema reached a peak at 48 hours after intracerebral hemorrhage. MMP-9 expression was significantly decreased in the mild hypothermia group compared with the normothermia group at each time point （P 〈 0.05）.
CONCLUSION： Mild hypothermia can significantly inhibit MMP-9 overexpression and reliev     

Mild hypothermia effects on matrix metalloproteinase-9 expression in the perihematomal region of rats following experimental intracerebral hemorrhage

BACKGROUND:Matrix metalloproteinase-9(MMP-9)expression increases with intracerebral hemorrhage,and participates in the pathophysiological processes of secondary brain injury after intracerebral hemorrhage.OBJECTIVE:To investigate the effects of mild hypothermia on MMP-9 expression and brain edema in the perihematomal region of experimental intracerebral hemorrhage rats.DESIGN,TIME AND SETTING:The randomized,controlled experiment was performed at the Central Laboratory of Shandong Provincial Hospital between May and September 2007.MATERIALS:Seventy-two,Wistar,male rats,12-weeks old,were used for this study.Rabbit anti-MMP-9 primary antibody was purchased from Boster,China.METHODS:Wistar rats were equally and randomly divided into normothermia and mild hypothermia groups.The two groups each comprised control,6-hour intracerebral hemorrhage,24-hour intracerebral hemorrhage,48-hour intracerebral hemorrhage,72-hour intracerebral hemorrhage,and 1-week intracerebral hemorrhage subgroups,with six rats in each subgroup.Rat models of intracerebral hemorrhage were established by irtjecting 100 μL of autologous blood into the rat caudate nucleus.Rats in the mild hypothermia group received four hours of local mild hypothermia immediately following the injection.Intracerebral temperature was maintained at(33±0.5)℃.Subsequently,intracerebral temperature was spontaneously recovered at 25℃.Rats in the control subgroup were not injected with autologous blood and received only with intracerebral hemorrhage.MAIN OUTCOME MEASURES:Brain water content and MMP-9 expression surrounding the hematoma region.RESULTS:MMP-9 expression increased at 6 hours,and brain edema reached a peak at 48 hours after intracerebral hemorrhage.MMP-9 expression was significantly decreased in the mild hypothermia group compared with the normothermia group at each time point (P<0.05).CONCLUSION:Mild hypothermia can significantly inhibit MMP-9 overexpression and relieve brain edema following intracerebral hemorrhage.     

微创清除血肿和重组水蛭素治疗脑出血后脑水肿的实验研究

目的探讨微创清除血肿和局部应用重组水蛭素对大鼠出血性脑水肿的治疗作用。方法成年雄性SD大鼠随机分为生理盐水组、脑出血组、微创组、水蛭素组、微创 水蛭素组,治疗时间点统一为出血后3h,以自体血注入大鼠尾状核方法建立脑出血模型,应用干-湿重法观察脑水肿变化,HE染色观察水肿细胞形态。每组每时相点(12h、24h、48h、72h、7d)6只大鼠。结果脑出血组和各治疗组脑含水量与生理盐水组在12h、24h、48h比,P<0.05;7d时各组间无明显差异(P>0.05);微创组与脑出血组组间比较,P>0.05;微创 水蛭素组与脑出血组组间比较,P<0.05。结论脑出血后早期(<3h)分别予以微创清除血肿、局部应用水蛭素及二者联合治疗可显著改善脑水肿,尤其微创与凝血酶抑制剂联合应用为脑出血治疗开辟新途径。