菸花苷对缺血性脑卒中大鼠的长期保护作用

目的 探讨菸花苷对缺血性脑卒中大鼠的长期保护作用。方法 建立大鼠脑缺血模型,观察菸花苷对于大鼠长期生存率、神经系统功能、体重及脑神经元的影响。结果 菸花苷可以显著提高脑缺血大鼠的长期生存率,促进大鼠体重增加,减轻脑组织病理损伤,维持脑神经元形态及神经系统功能。结论 菸花苷具有明显的对缺血性脑卒中大鼠的长期保护作用,其作用机制可能与保护脑神经元结构和功能有关。     

黄芩苷对脑组织缺血模型大鼠神经营养因子含量的影响

目的:研究黄芩苷抗脑缺血损伤的机制。方法:参照Longa法复制脑缺血大鼠模型,酶联免疫吸附法测定脑组织神经生长因子(NGF)、碱性成纤维细胞生长因子(bFGF)、脑源性神经营养因子(bDNF)3种神经营养因子(NTF)含量。结果:与假手术组比较,大鼠脑缺血12h和24h时,模型组脑组织3种NTF含量均反应性增加。与模型组比较,脑缺血12h时,黄芩苷组脑组织NGF、bFGF含量相似,bDNF含量显著降低(P<0.05);脑缺血24h时,黄芩苷组脑组织NGF、bDNF含量均降低,bFGF含量增加(P<0.05)。结论:黄芩苷对脑缺血损伤神经元的保护作用中,促进星形胶质细胞等产生bFGF可能是其主要途径。     

L-NAME reduces infarction,neurological deficit and blood-brain barrier disruption following cerebral ischemia in mice

The role of nitric oxide (NO) in the development of post-ischemic cerebral infarction has been extensively examined, but fewer studies have investigated its role in other outcomes. In the present study, we first determined the temporal evolution of infarct volume, NO production, neurological deficit and blood-brain barrier disruption in a model of transient focal cerebral ischemia in mice. We then examined the effect of the nonselective NO-synthase inhibitor N(omega)-nitro-L-arginine-methylester (L-NAME). L-NAME given at 3 mg/kg 3 h after ischemia reduced by 20% the infarct volume and abolished the increase in brain NO production evaluated by its metabolites (nitrites/nitrates) 48 h after ischemia. L-NAME with this protocol also reduced the neurological deficit evaluated by the grip test and decreased by 65% the extravasation of Evans blue, an index of blood-brain barrier breakdown. These protective activities of L-NAME suggest that NO has multiple deleterious effects in cerebral ischemia.     

复方白花前胡液对大脑中动脉缺血再灌注大鼠 Caspase-3蛋白表达的影响

目的 :探索复方白花前胡液对大脑中动脉缺血再灌注大鼠Caspase 3蛋白表达的影响。方法 :线栓法制备大脑中动脉缺血再灌注大鼠模型 ,术后2 4、4 8、72h分别检测大鼠的神经功能缺损 ;并采用免疫组织化学法检测凋亡相关基因Caspase 3蛋白表达。结果 :MCAO R 2 4、4 8、72h后 ,所有动物都出现程度不同的运动障碍 ,且大鼠脑组织中Caspase 3蛋白表达显著升高 ,复方白花前胡液可明显改善大脑中动脉缺血再灌注大鼠的神经功能缺损症状 ,抑制大鼠Caspase 3蛋白表达水平。结论 :复方白花前胡液能有效抑制凋亡相关基因Caspase 3蛋白的表达 ,减轻或消除缺血级联反应中迟发性神经元死亡 ,复方白花前胡液是其治疗缺血性中风病的机理之一。     

Down regulation of cyclooxygenase-2 is involved in delayed neuroprotection by ischemic preconditioning in rats

Aim: To examine whether the prostaglandins (PGs) pathway is involved in triggering delayed neuroprotection by ischemic preconditioning (IPC) and evaluate the effects of IPC on cyclooxygenase-2 (COX-2) expression following focal cerebral ischemia and reperfusion in rats. Methods: IPC was induced by 10min of saline infusion into the left internal carotid artery with the right common carotid artery clamped at the same time. Middle cerebral artery occlusion (MCAO) and reperfusion model was prodt:ced using intraluminal filament method. Results: IPC 48h priorto MCAO significantly reduced infarct area as compared with MCAO alone. A nonselective inhibitor of COX indomethacin (3mg/kg ip) applied 1h prior to or 1h after IPC failed to affect its protective effects. IPC had no direct effect on the cortex COX-2 mRNA and protein expression 72h later, but decreased the expression of COX-2 mRNA and protein following ischemia and reperfusion insult. Conclusion: PGs pathways was not involved in triggering delayed neuroprotection by IPC, and IPC induced down-regulation of COX-2 following focal cerebral ischemia and reperfusion in rats in vivo.     

阿坎酸对大鼠局灶性脑缺血/再灌注神经的保护作用

目的:研究阿坎酸对大鼠局灶性脑缺血-再灌注损伤的神经保护作用.方法:大鼠大脑中动脉栓塞模型参照Longa报道的方法进行.48只SD雄性大鼠随机分为假手术组、模型组、阿坎酸组.缺血2 h后恢复灌注,给药组腹腔注射给药.造模前后进行神经损害严重程度评分(NSS),TTC染色测定梗死面积,HE染色检测脑组织病理变化,应用蛋白质印迹检测大鼠脑组织中NR2B的表达.结果:阿坎酸能明显改善大鼠的神经行为,缩小梗死面积,并使脑组织病理改变减轻.同时,阿坎酸能有效降低NR2B的表达.结论:阿坎酸对局灶性脑缺血／再灌注大鼠有明显的保护作用.     

1,6-二磷酸果糖镁对大鼠脑缺血及再灌注损伤的保护作用(英文)

目的 :观察 1,6′ 二磷酸果糖镁 (FDP Mg)对大鼠短暂全脑缺血及再灌注损伤的影响。方法 :采用四血管 (即双侧颈总动脉 +双侧椎动脉 )闭塞法致全脑缺血及再灌注模型。结果 :与假手术组相比 ,生理盐水及FDP Mg组脑缺血再灌注后均出现不同程度的海马形态结构损伤及神经元细胞死亡。与生理盐水组相比 ,FDP Mg组再灌注 2 4h ,72h及 7d ,CA1区锥体细胞密度较生理盐水组正常形态的细胞数明显增多 (P <0 .0 1) ,海马周围胶质细胞浸润也明显减轻。结论 :FDP Mg对脑缺血后再灌注损伤有明显的保护作用     

依达拉奉对脑出血大鼠神经行为学、脑缺血面积及出血量的影响

目的：观察依达拉奉对大鼠脑出血后神经行为学、脑缺血面积及脑出血量的影响。方法：108只大鼠随机分为假手术组、模型组、胞磷胆碱组和依达拉奉高、中、低剂量组,采用Ⅶ型胶原酶诱导的大鼠脑出血模型,观测各组大鼠脑出血后12,24,48 h的神经行为学和48 h大鼠脑缺血面积及患侧大脑匀浆游离血红蛋白的含量。结果：与模型组相比,依达拉奉高剂量组各对应时间点的神经行为学分值显著降低,脑缺血面积亦显著缩小；中剂量组12 h和24 h时的神经行为学分值也降低；各组脑血红蛋白测定值与模型组相比均无显著差异。结论：依达拉奉注射液能有效减轻脑出血后神经功能缺损症状和出血后继发性缺血性损伤,但对出血量无明显影响。     

脑心通抑制脑缺血诱导的内质网凋亡通路

目的观察脑心通对大鼠缺血脑组织内质网凋亡通路caspase-12表达的影响,探讨其对大鼠局灶性脑缺血损伤的保护机制。方法采用线栓法制备大鼠局灶性脑缺血模型。大鼠随机分为假手术组、缺血组以及缺血后脑心通治疗组（n=30）,应用组织学观察、免疫组织化学方法及半定量RT-PCR检测缺血不同时段caspase-12表达变化。结果脑缺血6 h caspase-12转录表达增加,12 h达高峰,24h下降。脑心通治疗组与缺血组同时间在相同脑区比较caspase-12转录表达明显减少。假手术组caspase-12无表达。结论脑心通可抑制脑缺血所致的caspase-12凋亡通路,减轻脑缺血造成的损害。     

葛根黄豆苷元对沙土鼠脑缺血及再灌注损伤的神经保护作用(英文)

目的研究葛根黄豆苷元（DZ）对沙土鼠脑缺血及缺血再灌注损伤的保护作用。方法采用结扎沙土鼠左侧及两侧颈总动脉分别制备脑缺血及缺血再灌注损伤模型,术前20 min腹腔注射DZ(35、70 mg·kg^-1),双盲法记录沙土鼠脑缺血1、3、6h后卒中指数;组织学方法检查神经元的病理学损伤;脑缺血24 h及缺血10 min再灌24 h后,利用干燥称重法及原子吸收分光光度法测定脑内水、钙、钠离子的含量。结果与溶媒组相比,DZ能明显降低沙土鼠卒中指数,缓解缺血性脑神经元的损伤（P<0.05）。缺血24 h后,DZ治疗组沙土鼠脑组织内水、钙、钠含量明显低于溶媒组（P<0.05）。缺血10min再灌24 h后,与溶媒组相比,DZ也明显降低缺血再灌注沙土鼠脑组织中水、钙、钠的含量（P<0.05和P<0.01）。结论 DZ能改善沙土鼠脑缺血及缺血再灌注性脑损伤,其机制可能是减少钙、钠、水在脑细胞内的蓄积。     

三七皂甙对急性脑缺血的保护作用

三七总皂甙对沙土鼠脑缺血再灌流损伤有明显保护作用;能减少脑缺血45min再灌流6h的卒中指数,并降低再灌流24h的死亡率。三七总皂甙单体Rb_1对树鼩局部脑缺血有保护作用:能减轻树鼩局部脑缺血12h后的脑水肿,并降低缺血脑组织的钙含量及缩小梗塞范国,而三七总皂甙单体Rg_1的作用不明显。     

褪黑素对大鼠急性脑缺血再灌注损伤保护作用研究

目的　探讨褪黑素 (melatonin ,MT)对急性脑缺血再灌注损伤的保护作用及机制。方法　用线栓法制备大鼠大脑中动脉急性缺血再灌注损伤模型 ,再灌注 2 4h后测定大鼠脑组织中丙二醛 (malondialdehyde ,MDA)含量、超氧化物歧化酶 (superoxidedismutase,SOD)和髓化过氧化物酶(myeloperoxidaseMPO)活性以及血浆中血栓素B2 (throm boxaneB2 ,TXB2 )、6 酮 前列腺素F1α( 6 keto prostaglandinF1α,6 酮 PGF1α)含量。结果　MT 10、2 0mg·kg-1能保护SOD活性、减缓脑组织中MDA的升高 ,2 0mg·kg-1还可恢复血浆中TXB2 与 6 酮 PGF1α的平衡 ,减缓脑组织中MPO的升高。结论　MT对大鼠急性脑缺血再灌注损伤的保护作用与其提高抗氧化酶活性 ,抗脂质过氧化损伤及抗炎作用有关     

Protective effect of Nardostachys jatamansi in rat cerebral ischemia

The protective effect of Nardostachys jatamansi (NJ) on neurobehavioral activities, thiobarbituric acid reactive substance (TBARS), reduced glutathione (GSH), thiol group, catalase and sodium-potassium ATPase activities was studied in middle cerebral artery (MCA) occlusion model of acute cerebral ischemia in rats. The right MCA of male Wistar rats was occluded for 2 h using intraluminal 4-0 monofilament and reperfusion was allowed for 22 h. MCA occlusion caused significant depletion in the contents of glutathione and thiol group and a significant elevation in the level of TBARS. The activities of Na(+)K(+) ATPase and catalase were decreased significantly by MCA occlusion. The neurobehavioral activities (spontaneous motor activity and motor coordination) were also decreased significantly in MCA occlusion group. All the alternations induced by ischemia were significantly attenuated by 15 days pretreatment of NJ (250 mg/kg po) and correlated well with histopathology by decreasing the neuronal cell death following MCA occlusion and reperfusion. The study provides first evidence of effectiveness of NJ in focal ischemia most probably by virtue of its antioxidant property.     

化学诱导兔脑缺血模型早期MSCT灌注成像实验性研究

目的应用化学诱导方法建立稳定可靠的兔脑局部缺血模型,探讨早期缺血性脑梗死多层螺旋CT（MSCT）灌注成像表现与最终梗死体积的关系。方法对34只健康新西兰大白兔成功栓塞,然后分别于栓塞后15min、30min、1h行MSCT灌注成像扫描,2、4、6、8、10、12、24h行颅脑CT平扫观察。结果应用月桂酸钠化学诱导方法成功建立稳定、可靠的脑局部缺血模型,经病理HE染色证实神经元变性坏死明显,大量神经元固缩,并可见到神经元周围空泡样改变。MSCT灌注成像表现：实验兔梗塞后20～30minCT脑血流量（CBF）灌注图可以清楚地显示不同程度的缺血状态,兔脑两侧相比有明显的色阶变化,一侧大脑半球局部呈低灌注状态。继续跟踪观察2、4、6、8、10、12、24hCT平扫发现大部分最终梗死体积与灌注图像获得的梗死范围基本一致。结论应用月桂酸钠化学诱导方法可成功建立稳定可靠的脑梗死模型,MSCT灌注扫描CBF灌注图像可最早于梗死后15～20min发现脑梗死病灶,并且大部分与最终梗死体积基本一致。     

Acute neurovascular unit protective action of pinocembrin against permanent cerebral ischemia in rats

Acute vascular- and neuroprotective effects of pinocembrin (1) were evaluated in a rat model of focal cerebral ischemia. Focal cerebral ischemia was induced by the middle cerebral artery occlusion (MCAO) for 24 h. 5,7-Dihydroxyflavanone (compound 1; at 3, 10, or 30 mg/kg), intravenously injected at 0, 8, and 16 h after MCAO, reduced the cerebral infarct volumes by 47, 39, and 37%, respectively, as visualized by 2,3,5-triphenyltetrazolium chloride staining (P < 0.01). Treatment with 1 also reduced brain swelling and improved behavioral deficits significantly (P < 0.01 and 0.05, respectively). To evaluate the effect of 1 on blood-brain barrier (BBB) disruption, mixture of Evans Blue (EB) and sodium fluorescein (NF) was intravenously injected immediately after MCAO. Global NF/EB uptake and fluorescence imaging of local BBB disruption were measured. Treatment with compound 1 reduced the leakage of both dyes, manifesting a preventive action in BBB integrity. This is the first time to demonstrate that 1 has acute neurovascular protective action against permanent focal cerebral ischemia. The mechanism of neurovascular protective action of 1 is under investigation.     

西洛他唑对脑缺血后神经元损伤的保护作用

目的：观察西洛他唑对小鼠持续性局灶性脑缺血后神经元损伤的剂量依赖性保护作用。方法：以大脑中动脉阻塞诱导小鼠持续性局灶性脑缺血。缺血前30min腹腔注射西洛他唑（3～30mg/kg）和普鲁司特（0.1mg/kg）。观察药物对缺血后神经元形态、密度的影响。结果：脑缺血损伤后,神经元密度降低,变性神经元密度增加。西洛他唑（3～10mg/kg）和普鲁司特能明显增加缺血侧存活神经元密度,减少变性神经元密度。结论：西洛他唑对小鼠持续性局灶性脑缺血后神经元损伤有保护作用。     

Anti-inflammatory effects of PJ34, a poly(ADP-ribose) polymerase inhibitor, in transient focal cerebral ischemia in mice

BACKGROUND AND PURPOSE: Activation of poly(ADP-ribose) polymerase (PARP) is deleterious during cerebral ischemia. We assessed the influence of PARP activation induced by cerebral ischemia on the synthesis of proinflammatory mediators including the cytokines, tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) and the adhesion molecules, E-selectin and intercellular adhesion molecule-1 (ICAM-1). EXPERIMENTAL APPROACH: Ischemia was induced by intravascular occlusion of the left middle cerebral artery for 1 h in male Swiss mice anaesthetized with ketamine and xylazine. The PARP inhibitor PJ34 (1.25-25 mg kg(-1)) was administered intraperitoneally 15 min before and 4 hours after, the onset of ischemia. Animals were killed 6 h or 24 h after ischemia and cerebral tissue removed for analysis. KEY RESULTS: Ischemia increased TNF-alpha protein in cerebral tissue at 6 and 24 h after ischemia. All doses of PJ34 blocked the increase in TNF-alpha at 6 h and 25 mg kg(-1) PJ34 had a sustained effect for up to 24 h. Quantitative real time polymerase chain reaction showed that PJ34 (25 mg kg(-1)) reduced the increase in TNF-alpha mRNA by 70% at 6 h. PJ34 also prevented the increase in mRNAs encoding IL-6 (-41%), E-selectin (-81%) and ICAM-1 (-54%). PJ34 (25 mg kg(-1)) reduced the infarct volume (-26%) and improved neurological deficit, 24 h after ischemia. CONCLUSIONS AND IMPLICATIONS: PJ34 inhibited the increase in the mRNAs of four inflammatory mediators, caused by cerebral ischemia. The contribution of this effect of PJ34 to neuroprotection remains to be clarified.     

罗格列酮对大鼠脑缺血/再灌注损伤的保护作用

目的探讨罗格列酮对局灶性脑缺血/再灌注损伤的保护作用及其机制。方法线栓法制备大鼠大脑中动脉局灶性脑栓塞模型,缺血2h,再灌注24h。评价神经功能状态,测定脑梗死体积;分光光度法测定组织丙二醛(MDA)和一氧化氮(NO)含量以及一氧化氮合酶(NOS)、超氧化物歧化酶(SOD)和髓过氧化物酶(MPO)活性。免疫组化法测定细胞间粘附分子-1(ICAM-1)表达,HE染色观察组织病理学改变。结果罗格列酮能降低缺血再灌注后脑梗死体积,改善神经功能状态,降低脑组织MDA、NO含量,升高SOD活性并降低NOS、MPO活性以及组织ICAM-1表达,同时能减轻脑组织病理学损害。结论罗格列酮对大鼠脑缺血/再灌注损伤具有明显保护作用,其机制与其清除氧自由基和抗炎有关。     

果糖二磷酸钠镁对大鼠脑缺血/再灌注损伤的保护作用

目的 :研究果糖二磷酸钠镁对大鼠脑缺血/再灌注引起脑损伤的保护作用。方法 :自大鼠颈总动脉插入尼龙线栓栓塞大脑中动脉 ,造成大鼠脑缺血 ,缺血1h后拔出线栓实现再灌注。脑缺血10min后给予400mg/kg 果糖二磷酸钠镁 (FDPM )或400mg/kg1 ,6—二磷酸果糖 (FDP)或30mg/kg 硫酸镁 (MgSO4) ,分别于脑缺血1h再灌注2h、5h、23h时进行神经病学评分 ,并于脑缺血1h再灌注23h时测定脑梗塞面积及脑组织丙二醛 (MDA)含量 ,观察大鼠脑组织病理学变化。结果 :与模型组相比 ,FDPM组明显减低脑缺血/再灌注大鼠神经病学评分 ,缩小脑梗塞面积 ,降低脑组织MDA含量 ,减轻脑组织的病理改变 ,其作用强于FDP组和MgSO4 组。结论 :FDPM可显著保护大鼠脑缺血/再灌注引起的脑损伤。