Detrimental Effect of Electromagnetic Pulse Exposure on Permeability of In Vitro Blood-brain-barrier Model

Objective To study the effect of electromagnetic pulse （EMP） exposure on permeability of in vitro blood-brain-barrier （BBB） model. Methods An in vitro BBB model, established by co-culturing brain microvascular endothelial cells （BMVEC） and astroglial cells （AC） isolated from rat brain, was exposed to EMP at 100 kV/m and 400 kV/m, respectively. Permeability of the model was assayed by measuring the transendothelial electrical resistance （TEER） and the horseradish peroxidase （HRP） transmission at different time points. Levels of BBB tight junction-related proteins were measured at O, 1, 2, 4, 8, 12, 16, 20, 24 h after EMP exposure by Western blotting. Results The TEER level was lower in BBB model group than in control group at 12 h after EMP, exposure which returned to its normal level at 24 h. The 24 h recovery process was triphasic and biphasic respectively after EMP exposure at 100 kV/m and 400 kV/m. Following exposure to 400 kV/m EMP, the HRP permeability increased at 1-12 h and returned to its normal level at 24 h. Western blotting showed that the claudin-5 and ZO-1 protein levels were changed after EMP exposure. Conclusion EMP exposure at 100 kV/m and 400 kV/m can increase the permeability of in vitro BBB model and BBB tight junction-related proteins such as ZO-1 and claudin-5 may change EMP-induced BBB permeability.

Correlation of vascular endothelial growth factor to permeability of blood-brain barrier and brain edema during high-altitude exposure

BACKGROUND： Many studies have evaluated the role of vascular endothelial growth factor （VEGF） in traumatic brain edema and hemorrhagic brain edema. OBJECTIVE： To observe the effects of VEGF expression on permeability of the blood-brain barrier （BBB） during high-altitude and hypoxia exposure, and to investigate the correlation between VEGF expression and BBB permeability with regard to Evans blue staining and brain edema during high-altitude exposure. DESIGN, TIME AND SETTING： The randomized, controlled, animal study was performed at the Tanggula Etape, Central Laboratory of Chengdu Medical College, and Central Laboratory of General Hospital of Chengdu Military Area Command of Chinese PLA, China, from July 2003 to November 2004. MATERIALS： Quantitative RT-PCR kit （Sigma, USA）, VEGF ELISA kit （Biosource, USA）, and Evans blue （Jingchun, China） were acquired for this study. METHODS： A total of 180 Wistar rats were equally and randomly assigned to 15 groups： low-altitude （500 m）, middle-altitude （2 880 m）, high-altitude （4 200 m）, super-high-altitude （5 000 m）, 1,3, 5, 7, 9, 11, 13, 15, 17, 19, and 21 days of super high-altitude exposure. Wistar rats were exposed to various altitude gradients to establish a hypoxia model. MAIN OUTCOME MEASURES： Brain water content was calculated according to the wet-to-dry weight ratio. BBB permeability to Evans blue was determined by colorimetric method. VEGF mRNA and protein levels in brain tissues were detected using RT-PCR and double-antibody sandwich ELISA. RESULTS： Brain water content, BBB permeability to Evans blue, and VEGF mRNA and protein levels in brain tissues increased with increasing altitude and prolonged exposure to altitude. The greatest increase was determined on day 9 upon ascending 5 000 m. Simultaneously, VEGF expression positively correlated to BBB permeability of Evans blue and brain water content （r = 0.975, 0.917, P〈 0.01）. CONCLUSION： Increased VEGF protein and mRNA expression was responsible for increased BBB permeability, which may be an important mechanism underlying brain edema during high-altitude exposure.

Relationship of gelatinases-tight junction proteins and blood-brain barrier permeability in the early stage of cerebral ischemia and reperfusion

Gelatinases matrix metalloproteinase-2 and matrix metalloproteinase-9 have been shown to mediate claudin-5 and occludin degradation, and play an important regulatory role in blood-brain barrier permeability. This study established a rat model of 1.5-hour middle cerebral artery occlusion with reperfusion. Protein expression levels of claudin-5 and occludin gradually decreased in the early stage of reperfusion, which corresponded to the increase of the gelatinolytic activity of matrix metalloproteinase-2 and matrix metalloproteinase-9. In addition, rats that received treatment with matrix metalloproteinase inhibitor N-[（2R）-2-（hydroxamidocarbonylmethyl）-4-methylpenthanoyl]-L- tryptophan methylamide （GM6001） showed a significant reduction in Evans blue leakage and an inhibition of claudin-5 and occludin protein degradation in striatal tissue. These data indicate that matrix metalloproteinase-2 and matrix metalloproteinase-9-mediated claudin-5 and occludin degradation is an important reason for blood-brain barrier leakage in the early stage of reperfusion. The leakage of the blood-brain barrier was present due to gelatinases-mediated degradation of claudin-5 and occludin proteins. We hypothesized that the timely closure of the structural component of the blood-brain barrier （tight junction proteins） is of importance.

In vitro model of the blood-brain barrier established by co-culture of primary cerebral microvascular endothelial and astrocyte cells

Drugs for the treatment and prevention of nervous system diseases must permeate the bloodbrain barrier to take effect.In vitro models of the blood-brain barrier are therefore important in the investigation of drug permeation mechanisms.However,to date,no unified method has been described for establishing a blood-brain barrier model.Here,we modified an in vitro model of the blood-brain barrier by seeding brain microvascular endothelial cells and astrocytes from newborn rats on a polyester Transwell cell culture membrane with 0.4-μm pores,and conducted transepithelial electrical resistance measurements,leakage tests and assays for specific bloodbrain barrier enzymes.We show that the permeability of our model is as low as that of the bloodbrain barrier in vivo.Our model will be a valuable tool in the study of the mechanisms of action of neuroprotective drugs.

Changes in the permeability of blood brain barrier and endothelial cell damage after cerebral ischemia

OBJECTIVE： To investigate the effect of endothelial cells on the permeability of blood brain barrier （BBB） after brain injury and its effect mechanism. DATA SOURCES： We searched for the articles of permeability of BBB and endothelial cell injury after brain is- chemia, which were published between January 1982 and December 2005, with the key words of ＂cerebral ischemia damage,blood brain barrier （ BBB）,permeability,effect of endothelial cell （EC） and its variation mechanism＂in English. STUDY SELECTION： The materials were primarily selected. The articles related to the changes in the permeability of BBB and the effect of endothelial cells as well as the change mechanism after cerebral ischemia damage were chosen. Repetitive studies or review articles were excluded. DATA EXTRACTION： Totally 55 related articles were collected, and 35 were excluded due to repetitive or review articles, finally 20 articles were involved. DATA SYNTHESIS： The content or viewpoints of involved literatures were analyzed. Cerebral ischemia had damage for endothelial cells, such as the inflow of a lot of Ca2^＋, the production of nitrogen monoxide and oxygen free radical, and aggravated destruction of BBB. After acceptors of inflammatory mediators on cerebrovascular endothelial cell membrane, such as histamine, bradykinin , 5-hydroxytryptamine and so on are activated, endothelial cells shrink and the permeability of BBB increases. Its mechanism involves in the inflow of extracellular Ca^＋2and the release of intracellular Ca^2＋ in the cells. Glycocalyx molecule on the surface of endothelial cell, having structural polytropy, is the determinative factor of the permeability of BBB. VEGF, intensively increasing the vasopermeability and mainly effecting on postcapillary vein and veinlet, is the strongest known blood vessel permeation reagent. Its chronic overexpression in the brain can lead the destruction of BBB. CONCLUSION： The injury of endothelial cell participants in the pathological mechanism of BBB destruction after cerebral ischemla.

IMPAIRED BLOOD-BRAIN BARRIER AFTER CHRONIC CEREBRAL HYPOPERFUSION

Ohjectire To examine the hypothesis of normal perjusion pressure breakthrough (NPPB). Methods A modified Spetzler carotid -jugular (CJ) fistula model was created to imitate NPPB. In 9 male adult Sprague- Dawley rats, the ipsilateral vertebral artery and bilateral external carotid arteries were occluded. The period of hypoperfusion CJ fistula was extended to 14 weeks, as a modofcation of Spetzler model. The histological change were examtned under transmission electron microscope 14 weeks after creation of the listula. Results Ischemic histological changes such as increased pinocytosis, increased lucency of the basal lamina, and frank necrosis of the cerebral capillary were found in rats of CJ fistula group. Conclusion The findings in this study suggest that blood - braln barrier (BBB) was impaired by chronic hypoperfusion. The impaired BBB mny be one of the important causes of the NPPB phenomenon.

The effects of ultrasound on blood-brain barrier

The brain is protected from the entry of foreign substances by blood-brain barrier (BBB), but becomes a barrier while chemotherapy is needed for the brain diseases. Ultrasound with microbubbles (MBs) has been shown to noninvasively increase the permeability of the BBB in the normal tissue and brain tumor. The real mechanism for disruption is still unknown. Hemorrhage was usually found in the sonicated region of the brain. Thus, treatment safety is the primary concern when considering clinical application of BBB disruption induced by ultrasound in the presence of MBs. Here we investigate the effects of ultrasound on the permeability of BBB whether the MBs were administered. The data reveals that Evans blue (EB) accumulation was highest in the brain after sonication with MBs. However, the permeability of BBB also can be significantly increased by ultrasound alone. These results demonstrated that noninvasive disruption of BBB by ultrasound alone with no damage is possible.

Upregulated inflammatory associated factors and blood-retinal barrier changes in the retina of type 2diabetes mellitus model

AIM： To examine the expression of high mobility group box-1（HMGB-1） and intercellular adhesion molecule-1（ICAM-1） in the retina and the hippocampal tissues; and further to evaluate the association of these two molecules with the alterations of blood-retinal barrier（BRB） and blood-brain barrier（BBB） in a rat model of type 2 diabetes.METHODS： The type-2 diabetes mellitus（DM） model was established with a high-fat and high-glucose diet combined with streptozotocin（STZ）. Sixteen weeks after DM induction, morphological changes of retina and hippocampus were observed with hematoxylin-eosin staining, and alternations of BRB and BBB permeability were measured using Evans blue method. Levels of HMGB-1 and ICAM-1 in retina and hippocampus were detected by Western blot. Serum HMGB-1 levels were determined by enzyme-linked immunosorbent assay（ELISA）.RESULTS： A significantly higher serum fasting blood glucose level in DM rats was observed 2wk after STZ injection（P 〈0.01）. The serum levels of fasting insulin,Insulin resistance homeostatic model assessment（IRHOMA）,total cholesterol（TC）, total triglycerides（TG） and low density lipoprotein cholesterol（LDL-C） in the DM rats significantly higher than those in the controls（all P 〈0.01）.HMGB-1（0.96±0.03, P 〈0.01） and ICAM-1（0.76±0.12, P 〈0.05） levels in the retina in the DM rats were significantly higher than those in the controls. HMGB-1（0.83±0.13, P 〈0.01） and ICAM-1（1.15 ±0.08, P 〈0.01） levels in the hippocampal tissues in the DM rats were alsosignificantly higher than those in the controls. Sixteen weeks after induction of DM, the BRB permeability to albumin-bound Evans blue dye in the DM rats was significantly higher than that in the controls（P 〈0.01）.However, there was no difference of BBB permeability between the DM rats and controls. When compared to the controls, hematoxylin and eosin staining showed obvious irregularities in the DM rats.CONCLUSION： BRB permeability increases significantly in rats with type-2 DM, which may be associated with the up-regulated retinal expression of HMGB-1 and ICAM-1.

Acrylamide exposure impairs blood-cerebrospinal fluid barrier function

Previous studies show that chronic acrylamide exposure leads to central and peripheral neu- ropathy. However, the underlying mechanisms remained unclear. In this study, we examined the permeability of the blood-cerebrospinal fluid barrier, and its ability to secrete transthyretin and transport leptin of rats exposed to acrylamide for 7, 14, 21 or 28 days. Transthyretin levels in cerebrospinal fluid began to decline on day 7 after acrylamide exposure. The sodium fluorescein level in cerebrospinal fluid was increased on day 14 after exposure. Evans blue concentration in cerebrospinal fluid was increased and the cerebrospinal fluid/serum leptin ratio was decreased on days 21 and 28 after exposure. In comparison, the cerebrospinal fluid/serum albumin ratio was increased on day 28 after exposure. Our findings show that acrylamide exposure damages the blood-cerebrospinal fluid barrier and impairs secretory and transport functions. These changes may underlie acrylamide-induced neurotoxicity.

Protective effects of dl-3n-butylphthalide against diffuse brain injury

DI-3n-butyiphthalide can effectively treat cerebral ischemia; however, the mechanisms underlying the effects of dl-3n-butylphthalide on microcirculation disorders following diffuse brain injury remain unclear. In this study, models of diffuse brain injury were established in Sprague-Dawley rats with the vertical impact method. DI-3n-butylphthalide at 80 and 160 mg/kg was given via intraperitoneal injection immediately after diffuse brain injury. Ultrastructural changes in the cerebral cortex were observed using electron microscopy. Cerebral blood flow was measured by laser Doppler flowmetry, vascular density was marked by tannic acid-ferric chloride staining, vascular permeability was es- timated by the Evans blue method, brain water content was measured using the dry-wet method, and rat behavior was measured by motor function and sensory function tests. At 6, 24, 48, and 72 hours after administration of dl-3n-butylphthalide, reduced cerebral ultrastructure damage, in- creased vascular density and cerebral blood flow, and improved motor and sensory functions were observed. Our findings demonstrate that dl-3n-butylphthalide may have protective effects against diffuse brain injury by ameliorating microcirculation disorder and reducing blood-brain barrier dam- age and cerebral edema.

Magnetic resonance imaging and cell-based neurorestorative therapy after brain injury

Restorative cell-based therapies for experimental brain injury, such as stroke and traumatic brain injury,substantially improve functional outcome. We discuss and review state of the art magnetic resonance imaging methodologies and their applications related to cell-based treatment after brain injury. We focus on the potential of magnetic resonance imaging technique and its associated challenges to obtain useful new information related to cell migration, distribution, and quantitation, as well as vascular and neuronal remodeling in response to cell-based therapy after brain injury. The noninvasive nature of imaging might more readily help with translation of cell-based therapy from the laboratory to the clinic.

双重介导脑靶向脂质体增强荷载阿霉素的体外血-脑脊液屏障渗透率

目的探讨双重介导脑靶向脂质体(RVGPR9-SSL)作为递送载体对阿霉素(doxorubicin,DOX)血-脑脊液屏障(blood brain barrier,BBB)渗透率的影响,为脑部药物递送提供新的策略。方法利用前期构建的双重介导脑靶向脂质体(RVGPR9-SSL)作为载体包载DOX(DOX@RVGPR9-SSL)。培养脑毛细血管内皮细胞(brain microvascular endothelial cells,BMVEC),在体外构建BBB模型,通过4h渗漏实验、跨膜电阻值(transmembrane resistance value,TEER)测量、扫描透射电镜(scanning transmission electron microscope,SEM)观察细胞间的紧密连接等,鉴定体外BBB模型构建是否成功。在BBB模型构建成功后,利用荧光共振能量转移(fluorescence a resonance energy transfer,FRET),通过激光共聚焦显微镜,考察RVGPR9-SSL体跨越BBB后的完整性。通过对比分析脂质体给药前后,BBB的形态以及TEER值,考察RVGPR9-SSL跨越BBB后对BBB完整性的影响。通过荧光分光光度计,考察DOX@RVGPR9-SSL的BBB渗透率。结果RVGPR9-SSL的包封率为97.25%。构建的BBB模型的TEER值均>200Ω·cm 2,并通过SEM观察到BMVEC细胞排列紧密,存在着明显的紧密连接,说明体外BBB模型成功建立,可用于考察BBB渗透率。DOX@RVGPR9-SSL4h累积BBB渗透率>10%,显著高于游离DOX的4h累积BBB渗透率。给药后BBB与DOX@RVGPR9-SSL均能保持较好的完整性。结论RVGPR9-SSL可以显著提高所包载的DOX的BBB渗透率,并且具有较好的安全性,是非常有前景的脑部药物递送载体。

Development of Human in vitro Brain-blood Barrier Model from Induced Pluripotent Stem Cell-derived Endothelial Cells to Predict the in vivo Permeability of Drugs

An in vitro blood-brain barrier(BBB) model is critical for enabling rapid screening of the BBB permeability of the drugs targeting on the central nervous system.Though many models have been developed, their reproducibility and renewability remain a challenge. Furthermore, drug transport data from many of the models do not correlate well with the data for in vivo BBB drug transport.Induced-pluripotent stem cell(i PSC) technology provides reproducible cell resources for in vitro BBB modeling.Here, we generated a human in vitro BBB model by differentiating the human i PSC(hi PSC) line GM25256 into brain endothelial-type cells. The model displayed BBB characteristics including tight junction proteins(ZO-1,claudin-5, and occludin) and endothelial markers(von Willebrand factor and Ulex), as well as high transendothelial electrical resistance(TEER)(1560 X.cm2±230 X.cm2) and c-GTPase activity. Co-culture with primary rat astrocytes significantly increased the TEER of the model(2970 X.cm2 to 4185 X.cm2). RNAseq analysis confirmed the expression of key BBB-related genes in the hi PSC-derived endothelial cells in comparison with primary human brain microvascular endothelial cells,including P-glycoprotein(Pgp) and breast cancer resistant protein(BCRP). Drug transport assays for nine CNS compounds showed that the permeability of non-Pgp/BCRP and Pgp/BCRP substrates across the model was strongly correlated with rodent in situ brain perfusion data for these compounds(R2= 0.982 and R2= 0.9973,respectively), demonstrating the functionality of the drug transporters in the model. Thus, this model may be used to rapidly screen CNS compounds, to predict the in vivo BBB permeability of these compounds and to study the biology of the BBB.

紧密连接蛋白ZO-1、occludin和actin参与缺氧缺血诱导的血脑屏障通透性增加

目的探讨血脑屏障紧密连接(blood-brain barrier-tight junction,BBB-TJ)蛋白ZO-1、occludin和ac-tin在缺氧缺血诱导的血脑屏障(blood-brain barrier,BBB)通透性增加中的变化及其机制。方法利用人脐静脉内皮细胞系ECV304与星形胶质细胞(astrocytes,AS)共培养建立体外BBB模型,模型随机分为正常对照组和缺氧缺血两组。透射电镜观察两组间BBB-TJ的变化,直接免疫荧光观察细胞骨架蛋白actin分布的改变。γ计数仪检测大分子物质125I-牛血清白蛋白(125I-BSA)通透曲线观察BBB通透性的改变,Western blot检测细胞骨架蛋白actin,胞浆附着蛋白ZO-1,跨膜蛋白occludin的表达量的改变。结果透射电镜观察培养第10天的体外BBB模型,可见内皮细胞连接紧密,细胞间形成光滑、连续、较高密度的紧密连接。缺氧缺血后5 h,内皮细胞间连接开放,形成裂隙。直接免疫荧光下检测可见周边Actin丝带模糊,部分断裂,形成细胞间裂隙。缺氧缺血组125I-BSA的通透量增加,与对照组比较差异有统计学意义(P<0.01)。同时ZO-1的表达量显著减少,而occludin和actin的表达量无明显改变。结论缺氧缺血诱导occludin的位置分布改变和ZO-1的表达量减少进而促使actin蛋白发生重排,是导致缺氧缺血后BBB通透性增加的可能机制之一。

MMP-9和细胞骨架肌动蛋白参与缺氧缺血诱导的体外血脑屏障模型通透性增加

目的:探讨基质金属蛋白酶-9(MMP-9)和细胞骨架肌动蛋白(actin)在体外模拟缺氧缺血诱导的血脑屏障(BBB)模型通透性增高中的变化及其机制。方法:利用人脐静脉内皮细胞系ECV304与星型胶质细胞(AS)共培养建立体外大鼠BBB模型,模型随机分为正常对照组、缺氧缺血组、BB-1101预处理组。通过γ计数仪检测大分子物质[125I]-牛血清白蛋白([125I]-BSA)通透曲线观察BBB通透性的改变,直接免疫荧光和Western印迹法检测actin表达量及分布的改变,并利用金属蛋白酶抑制剂BB-1101探讨MMP-9是否参与缺氧缺血诱导的BBB通透性增加。结果:缺氧缺血刺激后5h,缺氧缺血组[125I]-BSA的通透量增加、MMP-9表达增加,与对照组比较有显著差异(P<0.01)。直接免疫荧光下观察周边actin丝带模糊,细胞间连接松散,出现裂隙,但表达总量没有变化。BB-1101预处理可以减轻缺氧缺血所致的MMP-9表达增加和对actin连接的破坏,[125I]-BSA通透量低于缺氧缺血组(P<0.01)。结论:缺氧缺血诱导MMP-9表达增加进而促使actin蛋白重组,是导致BBB通透性增加的机制之一。

脑损伤后高血糖对大鼠血-脑屏障通透性的影响

目的 :研究脑损伤后高血糖对大鼠血 脑屏障通透性的影响。方法 :雄性Wistar大鼠 4 0只 ,随机分为 4组 :正常对照组 (Ⅰ组 ) ,高血糖组 (Ⅱ组 ) ,脑损伤后正常血糖组 (Ⅲ组 ) ,脑损伤后高血糖组 (Ⅳ组 )。应用流体冲击装置制作大鼠脑损伤模型 ,然后分别对高血糖及正常血糖组的血 脑屏障结构的损伤的标记物伊文蓝含量进行测定。结果 :在相同脑损伤的情况下 ,高血糖组的伊文蓝含量明显高于正常血糖组 (P <0 .0 1) ;同时以上 2组的伊文蓝含量均高于正常对照组及高血糖组 (无脑损伤组 ,P <0 .0 0 1) ;而正常对照组与高血糖组的伊文蓝含量无明显差异 (P >0 .0 5 )。结论 :脑损伤后高血糖使大鼠血

大鼠C6脑胶质瘤血-脑屏障的硝酸镧示踪电镜研究

目的研究C6脑胶质瘤不同区域血-脑屏障(BBB)的超微结构特征及血-脑肿瘤屏障(BBTB)通透性增高的途径。方法运用成瘤3周SD大鼠C6脑胶质瘤动物模型,取肿瘤中心、肿瘤边缘、距肿瘤边界2mm以内及2mm以外的同侧大脑半球和对侧大脑半球脑皮质等五个部位的脑组织,采用外源性硝酸镧透射电镜示踪法,观察BBB/BBTB超微结构特征。结果La3+在肿瘤中心与边缘部充填并通过血管内皮细胞之紧密连接至血管腔外-脑间质裂隙内,距肿瘤边界2mm以内的同侧大脑半球脑组织也有La3+渗出至局部基底膜,而其它观察脑区La3+则完全封闭于血管腔内;各部位脑血管内皮细胞胞浆内均无La3+;BM呈线状连续,管腔内无瘤细胞。结论C6胶质瘤紧密连接开放导致BBTB通透性增高;C6胶质瘤诱导的屏障功能破坏随其至肿瘤距离的增加而减弱。

大脑中动脉阻塞大鼠MMP-9基因表达及补阳还五汤对其影响

目的 :探讨脑缺血再灌后血脑屏障 (bloodbrainbarrier ,BBB)通透性、金属基质蛋白酶 9(matrixmetalloproteinase 9,MMP 9)基因表达的变化 ,及补阳还五汤对其影响。方法 :采用大鼠大脑中动脉阻塞 (middlecerebralarteryocclusion ,MCAO)模型 ,设假手术组、模型组和模型 +补阳还五汤组 ,于再灌 1h、3h、2 4h、4 8h、5d测定。结果 :模型 +补阳还五汤组BBB通透性及MMP 9mRNA较模型组表达降低。结论 :补阳还五汤可以保护BBB ,其作用可能和抑制MMP 9在缺血脑组织中的表达有关。

血管紧张素1-7对蛛网膜下腔出血后血脑屏障通透性的保护作用

目的分析血管紧张素Ang-(1-7)对蛛网膜下腔出血(SAH)后血脑屏障通透性的作用及机制。方法枕大池二次注血法制备SAH大鼠,伊文思蓝(Evans blue)检测Ang-(1-7)处理后SAH大鼠血脑屏障通透性及脑组织含水量;实时荧光定量PCR(RT-PCR)与蛋白免疫印迹法(Western blot)分析脑组织黏连蛋白ICAM-1、VCAM-1的表达。人工血性脑脊液(BCSF)刺激血管内皮细胞(HBMEC),检测细胞通透性及细胞增殖与凋亡情况。结果 Ang-(1-7)可降低SAH大鼠脑组织中Evans blue渗透量及脑组织含水量,具有剂量和时间依赖性,以10^(-5) mol/L Ang-(1-7)处理24h时变化最为显著,SAH大鼠脑组织中ICAM-1、VCAM-1表达水平显著上调。同时Ang-(1-7)作用的BCSF刺激的血管内皮细胞中Evans blue的渗透量明显减少,ICAM-1、VCAM-1的表达水平及细胞增殖活力显著增加,细胞凋亡减少。结论 Ang-(1-7)具有保护蛛网膜下腔出血后血脑屏障通透性作用。

芍药苷对纤维状Aβ1-42介导的血脑屏障体外模型损伤的影响

目的：探究芍药苷对纤维状Aβ1-42介导的血脑屏障体外模型损伤的影响。方法：（1）利用MTT法检测芍药苷对Aβ1-42介导的b End.3细胞活力的影响;（2）利用免疫组化法鉴定原代提取的星形胶质细胞;（3）利用b End.3细胞与原代星形胶质细胞体外非接触式体外共培养模型,通过测定各组透过共培养模型的荧光素钠强度,评价芍药苷对纤维状Aβ1-42介导的血脑屏障体外模型通透性的影响。结果：与模型组相比,芍药苷低、中、高剂量组能显著提高b End.3细胞活性,差异均具有统计学意义（P〈0.05）,其中低、中剂量组的保护作用与芍药苷浓度成正相关,而高剂量组有所下降;芍药苷低、中、高剂量组均能降低血脑屏障的通透性,而低、中剂量组与模型组相比差异具有统计学意义（P〈0.05）。结论：芍药苷对Aβ1-42诱导的血脑屏障通透性增加具有明显的抑制作用。