脑缺血耐受大鼠促红细胞生成素和缺氧诱导因子-1α的表达及其相关性

目的 研究脑缺血预处理诱导脑缺血耐受大鼠促红细胞生成素(EPO)及缺氧诱导因子(HIF-1α)的表达及其相关性.方法 采用二次线栓法制作大鼠脑缺血预处理与缺血再灌注模型(预缺血组),分别在短暂预缺血后1 d、3 d、7 d、14 d、21 d行脑缺血再灌注处理.用TTC染色测定脑梗死体积;逆转录聚合酶链反应(RT-PCR)检测大鼠脑内EPO mRNA 、HIF-1α mRNA的表达;并与无缺血预处理组(无预缺血组)比较.结果 预缺血组1 d、3 d、7 d亚组的脑梗死体积较无预缺血组明显减小(均P＜0.05) .预缺血组3 d、7 d亚组大鼠脑EPO mRNA、HIF-1α mRNA表达明显高于无预缺血组的相应各亚组(均P＜0.05);两组1 d、14 d、21 d亚组的差异无统计学意义.EPO mRNA与HIF-1α mRNA的表达呈正相关(r=0.737,P＜0.01).结论 缺血预处理可使EPO及HIF-1α表达在脑缺血后明显增高,两者的表达呈正相关.这可能是缺血预处理诱导脑缺血耐受形成的机制之一.     

局灶性缺血预处理对脑缺血大鼠血管内皮生长因子表达及血管形成的影响

目的：探讨血管内皮生长因子（VEGF）在脑缺血耐受中的作用及其与血管形成的关系。方法：Wistar大鼠线栓法阻塞大脑中动脉建立局灶性缺血预处理模型,并进行神经功能评分。随机分为假手术（对照组）、非缺血预处理（NIP）组和缺血预处理（IP）组,NIP和IP组再根据不同时间窗随机分成5个亚组。分别在缺血预处理后1、3、7、14和21 d进行再次缺血2 h再灌注22 h,然后取脑检测：TTC染色测定脑梗死体积,计数微血管密度,免疫组化检测CD34和VEGF蛋白表达,原位杂交法检测VEGF mRNA表达。结果：①组间比较：IP 1、3和7 d亚组脑梗死体积较NIP组明显减小（P〈0.01）,其神经行为缺损评分也明显降低（P〈0.05）;IP 3和7 d亚组脑微血管密度明显增高（P〈0.05）;IP 1、3和7 d亚组VEGF蛋白及mRNA表达明显增高（P〈0.05,P〈0.01）。②组内比较：IP 7 d亚组微血管在缺血灶周边区分布最为密集,脑微血管密度明显高于同组内其他亚组（P〈0.05）;IP 3和7 d亚组VEGF蛋白表达明显增高,VEGF mRNA表达在IP 1 d即开始升高,高峰出现在IP 3 d,持续至7 d。结论：缺血预处理诱导了脑缺血耐受,缺血预处理诱导的VEGF表达增加以及血管形成在脑缺血耐受中发挥重要作用。     

缺氧诱导因子-1α及促红细胞生成素在脑缺血耐受大鼠中的表达

目的 探讨缺氧诱导因子-1α（HIF-lα）及其靶基因促红细胞生成素（EPO）在脑缺血预处理诱导的大鼠脑缺血耐受机制中的作用。方法 将84只Wistar大鼠随机分成假手术对照组（SS+SS,4只）、假手术＋再缺血组（SS+MCAO,40只）、预缺血＋再缺血组（IP+MCAO,40只）,后两组再随机分成5个亚组。线栓法阻塞大脑中动脉建立局灶性缺血预处理模型（预缺血10 min）,分别在预缺血后1 d、3 d、7 d、14 d、21 d进行再次缺血2 h再灌注22 h,然后取脑组织进行脑梗死体积测量和病理观察,免疫组化方法检测HIF-lα与EPO蛋白的表达。结果 ⑴IP+MCAO组中1 d、3 d、7 d亚组的梗死体积与SS+MCAO各对应亚组相比明显减小;⑵IP+MCAO组1 d、3 d、7 d亚组中HIF-lα蛋白表达与SS+MCAO各对应亚组相比明显增高;IP+MCAO组3 d、7 d亚组中EPO蛋白表达与SS+MCAO各对应亚组相比明显增高。结论 缺血预处理诱导了脑缺血耐受,预缺血诱导的内源性HIF-lα及EPO蛋白表达增加参与脑缺血耐受形成的机制。     

短暂性脑缺血预处理诱导脑缺血耐受大鼠VEGF和Ang-1的表达变化

目的观察血管内皮生长因子(VEGF)和血管生成素-1(Ang-1)在短暂性脑缺血预处理(IP)诱导脑缺血耐受中的作用。方法 Wistar大鼠随机分成假手术对照组(9只)、非缺血预处理组(NIP,45只)、缺血预处理组(IP,45只),后两组再随机分成5个亚组。线栓法阻塞大脑中动脉建立局灶性缺血预处理模型,分别在缺血预处理后1、3、7、14、21d进行再次缺血2h再灌注22h,取脑检查。TTC染色测定脑梗死体积,免疫组织化学法检测VEGF、Ang-1蛋白表达。结果 (1)组间比较:IP组1、3、7d亚组梗死体积较NIP组明显减小(P<0.01),其神经行为缺损评分也明显降低(P<0.05);IP组1、3、7d亚组VEGF蛋白表达明显增高;而IP组7d亚组Ang-1蛋白表达明显增高(P<0.05)。(2)组内比较:IP组3d亚组梗死体积减小最为明显;3、7d亚组VEGF蛋白表达明显增高(P<0.05)。结论短暂性脑缺血预处理诱导脑缺血耐受的产生,VEGF和Ang-1在缺血预处理产生脑缺血耐受的相应时间窗内表达有所增加。     

肢体远隔缺血适应对大鼠缺血再灌注后脑水肿的影响

目的探讨肢体远隔缺血适应对局灶性脑缺血大鼠脑水肿的影响及其机制。方法利用线栓法制作脑缺血/再灌注模型,再灌注48 h后进行神经功能评分,采用干湿重法比较对照组与肢体缺血治疗组(LRIC)脑含水量、应用伊文思蓝法(Evans Blue,EB)观察血脑屏障(BBB)通透性,2,3,5氯化三苯基四氮唑蓝(2,3,5 triptriphemyltetrazolium chloride,TTC)法比较脑梗死面积。蛋白印迹法检测金属硫蛋白酶9(matrix metalloproteinase-9,MMP-9)、金属硫蛋白酶组织抑制因子1(TIMP-1)及水通道蛋白的表达。结果 LRIC治疗组的脑含水量、血脑屏障通透性、脑梗死体积、神经功能缺损程度均比对照组明显降低(P<0.05)。与对照组相比,LRIC组的MMP-9的蛋白表达明显降低,然而水通道蛋白-4及水通道蛋白-9均无变化。结论 LRIC能够降低大鼠脑缺血再灌注后脑水肿,其作用机制与抑制MMP-9相关,可能与水通道蛋白无相关性。     

白藜芦醇对大鼠缺血再灌注损伤后脑组织的保护作用

目的探讨白藜芦醇对大鼠缺血再灌注损伤后脑组织的保护作用及其机制。方法利用线栓法制作大鼠脑缺血再灌注损伤模型。72只SD大鼠按随机数字表法随机平均分为假手术组、对照组、白藜芦醇高剂量组和白藜芦醇低剂量组。缺血2h再灌注24h后,分别测定动物的神经损伤功能评分、脑组织梗死体积,缺血再灌注损伤的脑组织中髓过氧化物酶(MPO)的活性、伊文思兰的含量、肿瘤坏死因子-α(TNF-α)的含量及基质金属蛋白酶-9(MMP-9)的表达水平。结果白藜芦醇治疗组神经功能损伤评分均较对照组明显降低(P<0.05),脑梗死体积明显缩小(P<0.05),MPO的活性、伊文思兰的含量、TNF-α的含量及MMP-9表达水平均也明显低于对照组(P<0.05)。结论白藜芦醇可能通过降低炎症反应和血脑屏障通透性对大鼠脑缺血再灌注损伤的脑组织起神经保护作用;其抗炎作用可能与其降低TNF-α的含量有关,而降低血脑屏障通透性则可能与MMP-9的表达下调有关。     

全反式维甲酸对缺血再灌注大鼠血脑屏障通透性的影响

目的探究全反式维甲酸对缺血再灌注大鼠血脑屏障通透性的影响。方法将180只健康雄性大鼠完全随机分为假手术组(Sham),缺血再灌注组(I/R)和全反式维甲酸干预组(ATRA),每组60只,使用Zea Longa法制作局灶性脑缺血再灌注模型。在维甲酸干预(30 mg/kg)后不同时间点(1 d、3 d、7 d)分别通过测定大鼠脑梗死体积、伊文思蓝(EB)含量、基质金属蛋白酶-9(MMP-9)的表达来观察大鼠血脑屏障通透性的变化。结果缺血再灌注后脑梗死体积及EB含量均在1 d达高峰,之后逐渐下降,1 d及7 d时ATRA组脑梗死体积及EB含量均明显低于I/R组(P0.05)。MMP-9的表达3 d达高峰,免疫组化法显示3 d和7 d时ATRA组低于I/R组(P0.05),免疫印迹法显示1 d、3 d、7 d时ATRA组低于I/R组(P0.05)。结论全反式维甲酸可以减轻再灌注后血脑屏障的破坏。     

缺血预处理对脑缺血大鼠血管内皮生长因子表达及微血管密度变化的影响

目的 观察局灶性缺血预处理诱导脑缺血耐受大鼠血管内皮生长因子（vascular endothelial growth factor,VEGF）的表达及微血管密度（MVD）的变化。方法 将99只Wistar大鼠随机分成对照组9只、非缺血预处理（non-ischemic preconditioning,NIP）组45只、缺血预处理（ischemic preconditioning,IP）组45只,后两组按照再灌注时间随机分成1 d,3 d,7 d,14 d,21 d,5个亚组,每亚组9只大鼠。对IP组采用线栓法阻塞大鼠大脑中动脉建立局灶性IP模型,分别在IP后1 d,3 d,7 d,14 d,21 d对大鼠进行再次缺血2 h再灌注22 h,然后取脑检查。测定脑梗死体积,免疫组化检测MVD变化,原位杂交法检测VEGF信使核糖核酸（messenger RNA,mRNA）表达。结果 ①组间比较：对照组无梗死灶,未见有VEGF mRNA表达,IP组1 d,3 d,7 d亚组梗死体积较NIP组相应亚组明显减小（P均为0.001）。IP组1 d,3 d,7 d亚组VEGF mRNA较NIP组相应亚组表达明显增高（P分别为0.002、0.001、0.001）,IP组3 d,7 d亚组MVD较NIP组相应亚组表达明显增高（P分别为0.012、0.001）。②组内比较：IP组3 d亚组梗死体积减小最为明显,明显小于同组内其他亚组（与1 d、7 d、14 d、21 d亚组相比,P分别为0.001、0.042、0.001、0.001）;7 d亚组微血管在缺血灶周边区分布最为密集,MVD明显高于同组内其他亚组（与1 d、3 d、14 d、21 d亚组相比,P分别为0.001、0.003、0.004、0.001）;VEGF mRNA在IP后1 d表达即开始升高,高峰出现在IP后3 d,持续至7 d,且IP组3 d亚组VEGFmRNA表达明显高于同组内其他亚组（与1 d、7 d、14 d、21 d亚组相比,P分别为0.001、0.038、0.007、0.005）。③VEGF mRNA表达与MVD变化呈一定正相关性（r =0.472,P =0.017）。结论 VEGF mRNA及MVD在缺血预处理诱导大鼠脑缺血耐受的相应时间点内表达有所增加,VEGF及微血管形成可能在脑缺血耐受中发挥了重要作用。     

局灶性缺血预处理对脑梗死大鼠神经生长因子表达的影响

目的:研究局灶性缺血预处理对脑梗死大鼠神经生长因子(nerve growthfactor,NGF)表达的影响,探讨缺 血预处理诱导脑缺血耐受机制。方法:SD大鼠随机分为3组。预缺血组和假手术组在大脑中动脉缺血(MCAO)前3天 分别接受10min的预缺血或假手术,MCAO 2h后再灌注22h处死;对照组两次均为假手术,比较各组神经功能评分、梗 死体积及NGF的表达。结果:预缺血组神经功能评分、梗死体积较假手术组减少(P<0．05),NGF表达明显高于其余两 组(P<0．01)。结论:局灶性缺血预处理可诱导脑缺血耐受的产生,其作用机制可能与NGF的表达改变有关。     

腺苷预处理对大鼠脑缺血再灌注损伤后VEGF的表达

目的通过观察腺苷预处理后大鼠局灶性脑缺血再灌注区脑组织的病理结构、脑梗死面积及血管内皮生长因子(VEGF)的表达,探讨腺苷预处理诱导脑缺血耐受的可能作用机制。方法制作大鼠脑缺血再灌注损伤模型。60只SD大鼠随机分为3组:假手术组(F组)、缺血再灌注组(IR组)、腺苷预处理组(AP组),再按缺血再灌注后不同时间把各组随机分成4个亚组(每亚组5只大鼠)。通过TTC染色观察脑梗死体积,并应用免疫组化法检测各组大鼠脑组织VEGF的表达。结果 (1)TTC染色正常脑组织呈鲜红色,梗死区脑组织呈苍白色,并且随着再灌注时间的延长可见梗死区扩大,腺苷预处理组的脑梗死体积小于缺血再灌注组。(2)F组可见少量VEGF阳性表达,IR组和AP组在脑缺血再灌注后2 h开始出现VEGF阳性表达的细胞数量增多,24 h达到高峰,72 h下降,AP组在6 h、24 h VEGF阳性表达比IR组增强(P均<0.05),在72 h时AP组VEGF阳性表达较IR组减少(P<0.05)。结论腺苷预处理能够进一步增强大鼠局灶性脑缺血再灌注损伤后VEGF的表达;VEGF的表达增加可能是腺苷预处理诱导脑缺血耐受和产生神经保护作用的分子机制之一。     

Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 expression in early focal cerebral infarction following urokinase thrombolysis in rats

Activity of matrix metalloproteinase-9 increases following cerebral ischemia/reperfusion,and is associated with cerebral microvascular permeability,blood-brain barrier destruction,inflammatory cell infiltration and brain edema.Matrix metalloproteinase-9 also likely participates in thrombolysis.A rat model of middle cerebral artery infarction was established by injecting autologous blood clots into the internal carotid artery.At 3 hours following model induction,urokinase was injected into the caudal vein.Decreased neurological severity score,reduced infarct volume,and increased expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 were observed in the cerebral cortex 24 hours after urokinase thrombolysis.These results suggest that urokinase can suppress damage in the acute-early stage of cerebral infarction.     

Effects of ischemic preconditioning on blood-brain barrier permeability and MMP-9 expression of ischemic brain

The study was designed to investigate the effects of ischemic preconditioning (IP) on permeability of blood-brain barrier (BBB) and expression of matrix metalloproteinase-9 (MMP-9) in subsequent ischemic hemisphere. Rats were divided into four groups, one group was used as control, and the other three groups were given three different pretreatments: the first group received a saline injection into the right internal carotid artery (SI), the second group underwent both left and right carotid arteries occlusion (BCAO), and the third group was treated with BCAO and SI simultaneously (BS). After 24 hours of pretreatments, the focal cerebral ischemia was induced by inserting a thread into the right middle cerebral artery causing occlusion (MCAO). Brain water content, BBB permeability and MMP-9 expression of ischemic hemisphere brains were measured at 24 and 48 hours after MCAO. After 24 and 48 hours MCAO, averages for brain water content were 82.92 and 83.12% in BS group, 85.19 and 85.73% in SI group and 86.06 and 85.88% in BCAO group. Evans blue content of ischemic hemispheres were 14.01 and 11.74 microg/mm(3) at 24 and 48 hours after MCAO in BS group, which were lower than the other two groups, 16.22, 15.01 and 16.61, 15.58 microg/mm(3), respectively (p<0.01). The expression levels of MMP-9 in ischemic hemisphere in BS were lower than that in other two groups (p<0.01). Therefore, ischemic preconditioning could ameliorate brain edema and BBB disruption caused by subsequent cerebral ischemia. Ischemic preconditioning could decrease MMP-9 protein and mRNA expression, which may be an important mechanism of cerebral ischemic tolerance.     

Inflammatory response and neuronal necrosis in rats with cerebral ischemia

In the middle cerebral artery occlusion model of ischemic injury, inflammation primarily occurs in the infarct and peripheral zones. In the ischemic zone, neurons undergo necrosis and apoptosis, and a large number of reactive microglia are present. In the present study, we investigated the pathological changes in a rat model of middle cerebral artery occlusion. Neuronal necrosis appeared 12 hours after middle cerebral artery occlusion, and the peak of neuronal apoptosis ap- peared 4 to 6 days after middle cerebral artery occlusion. Inflammatory cytokines and microglia play a role in damage and repair after middle cerebral artery occlusion. Serum intercellular cell adhesion molecule-1 levels were positively correlated with the permeability of the blood-brain barrier. These findings indicate that intercellular cell adhesion molecule-1 may be involved in blood-brain barrier injury, microglial activation, and neuronal apoptosis. Inhibiting blood-brain barrier leakage may alleviate neuronal injury following ischemia,     

脑血疏口服液对大鼠脑缺血再灌注损伤后血脑屏障的影响

目的 探讨脑血疏口服液对大鼠脑缺血再灌注损伤后血脑屏障的影响。方法 将120只SD大鼠随机分为3组:假手术组、对照组,脑血疏组; 采用线栓法建立大鼠左侧大脑中动脉闭塞再灌注模型,缺血2 h后拔出线栓,恢复灌注24 h; 采用Longa FZ 5级评分法进行大鼠神经功能缺损评分; TTC染色计算脑梗死体积百分比; 运用干-湿重法测脑含水率; 通过伊文思蓝( EB)含量反映血脑屏障的损伤程度; 免疫组化检测基质金属蛋白酶-9(MMP-9)的表达水平。结果(1)假手术组大鼠在神经功能缺损评分、脑梗死体积、脑含水率均低于对照组(P<0.01); 脑组织中EB含量和MMP-9表达水平较对照组低(P<0.01);(2)脑血疏组大鼠的神经功能缺损评分较低、脑梗死体积较小,脑水肿程度较轻; EB含量和MMP-9表达水平均较对照组明显减少(P<0.01)。结论 脑血疏口服液对大鼠脑缺血再灌注损伤后血脑屏障具有保护作用,其机制可能是通过抑制MMP-9的表达。     

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.     

Matrix metalloproteinase-9 expression and blood brain barrier permeability in the rat brain after cerebral ischemia/reperfusion injury

BACKGROUND: The integrity of the blood brain barrier (BBB) plays an important role in the patho-physiological process of cerebral ischemia/reperfusion injury. It has been recently observed that metalloproteinase-9 (MMP-9) is closely related to cerebral ischemia/reperfusion injuryOBJECTIVE: This study was designed to observe MMP-9 expression in the rat brain after cerebral ischemia/reperfusion injury and to investigate its correlation to BBB permeability.DESIGN, TIME AND SETTING: This study, a randomized controlled animal experiment, was performed at the Institute of Neurobiology, Central South University between September 2005 and March 2006.MATERIALS: Ninety healthy male SD rats, aged 3-4 months, weighing 200-280g, were used in the present study. Rabbit anti-rat MMP-9 polyclonal antibody (Boster, Wuhan, China) and Evans blue (Sigma, USA) were also used.METHODS: All rats were randomly divided into 9 groups with 10 rats in each group: normal control group, sham-operated group, and ischemia for 2 hours followed by reperfusion for 3,6,12 hours, 1,2,4 and 7 days groups. In the ischemia/reperfusion groups, rats were subjected to ischemia/reperfusion injury by suture occlusion of the right middle cerebral artery. In the sham-operated group, rats were merely subjected to vessel dissociation. In the normal control group, rats were not modeled.MAIN OUTCOME MEASURES: BBB permeability was assessed by determining the level of effusion of Evans blue. MMP-9 expression was detected by an immunohistochemical method.RESULTS: All 90 rats were included in the final analysis. BBB permeability alteration was closely correlated to ischemia/reperfusion time. BBB permeability began to increase at ischemia/reperfusion for 3 hours, then it gradually reached a peak level at ischemia/reperfusion for 1 day, and thereafter it gradually decreased. MMP-9 expression began to increase at ischemia/reperfusion for 3 hours, then gradually reached its peak level 2 days after perfusion, and thereafter it gradually decreased.CONCLUSION: MMP-9 expression increases in rat brain tissue after focal cerebral ischemia/reperfusion injury, which correlates with increased permeability of the BBB.     

核因子—κB(NF—κB)在大鼠局灶性脑缺血耐受产生中的意义

目的:通过观察局灶脑缺血预处理对核因子κB(nuclear factor—κB,NF—κB)表达的影响初步探讨其在脑缺血耐受中的意义。方法:SD大鼠随机分为三组,对照组给予两次相前3天的假手术,其余两组分别在2小时大脑中动脉缺血(MCAO)及22小时再灌注前3天给予10分钟的预缺血或假手术,比较各组梗死体积、组织病理变化及NF—κB的表达。结果:预缺血组梗死体积较假手术组减小53.15％(p〈0.01),神经元损伤、坏死轻于后者,NF—κB表达低于假手术组及对照组(p〈0.01)。结论:10分钟大脑中动脉预缺血可有效诱导缺血耐受,减小梗死体积,减轻缺血性神经损伤,抑制NF—κB表达。NF—κB表达下调可能是局灶性脑缺血耐受产生的分子机制之一。     

3-硝基丙酸预处理对大鼠局灶性脑缺血神经元凋亡的影响

目的 :探讨小剂量线粒体毒素 3 硝基丙酸 ( 3 nitoppropionicacid ,3 NPA)预处理对大鼠局灶性脑缺血脑梗死体积 ,脑缺血半暗带神经元凋亡的影响 ,阐明 3 NPA预处理诱导脑缺血耐受的机制。方法 :大鼠腹腔注射 3 NPA 3d后制作大脑中动脉闭塞模型 ,采用TTC染色、TUNEL法和流式细胞术 ,观察 3 NPA预处理对缺血 2h再灌注 2 4h脑梗死体积、神经元凋亡的影响。结果 :缺血 2h再灌注 2 4h ,3 NPA预处理组脑梗死体积变小 ,神经元凋亡减少 ,与对照组比有显著性差异。结论 :3 NPA预处理可以诱导脑缺血耐受 ,抑制神经元凋亡可能是其机制之一     

神经节苷脂对大鼠脑缺血再灌注损伤的脑保护作用

目的探讨神经节苷脂对大鼠脑缺血再灌注损伤的脑保护作用。方法采用线栓法制作缺血再灌注大鼠模型,分别用神经节苷脂(治疗组)和生理盐水(对照组)腹腔注射。观察两组大鼠缺血90min、缺血90min再灌注24h的脑梗死面积、神经功能缺损程度、细胞凋亡数、细胞凋亡率。结果治疗组大鼠于相同时间点脑梗死面积较对照组明显减小,仅表现轻度的神经功能缺损,且神经细胞的凋亡数较对照组显著减少(均P<0.01)。结论神经节苷脂能明显减小大鼠实验性脑缺血的脑梗死面积,减轻脑缺血再灌注后神经功能缺损程度,显著减轻缺血区神经元损害,具有显著的脑保护作用。