1-(2,6-二甲基苯氧基)-2-(3,4-二甲氧基苯乙胺基)丙烷盐酸盐对麻醉猫、大鼠心肌缺血再灌注所致心律失常的作用

DDPH是具有α肾上腺素受体阻断作用和较弱抗钙作用的新化合物。本实验研究了DDPH对麻醉猫、大鼠心肌缺血再灌注所致心律失常的作用和对猫血压的影响。结果表明,DDPH iv 0.5～3 mg/kg可降低麻醉猫血压,减少麻醉猫冠状动脉左前降支结扎时心肌缺血产生的VEB,减少麻醉猫和大鼠再灌注所致VEB和VT,VF的持续时间,降低VT,VF的发生率。对动物再灌注时由VF引起的死亡率也有降低的趋势。与哌唑嗪比较,两者具有相似的抗麻醉猫和大鼠心肌缺血再灌注所致心律失常的作用。     

瓜蒌提取物对缺血缺氧及缺血后再灌注损伤心肌的保护作用

以异丙肾上腺素致小鼠常压缺氧模型、垂体后叶素致大鼠急性心肌缺血模型及大鼠心肌缺血再灌注模型 ,对瓜蒌提取物抗心肌缺氧缺血及缺血后再灌注损伤的作用进行探讨 .实验结果表明瓜蒌提取物能延长异丙肾上腺素作用的小鼠常压缺氧存活时间 ,对抗垂体后叶素所致的大鼠急性心肌缺血作用 ,并能显著保护缺血后再灌注损伤的大鼠 .     

薤白提取物对心肌缺氧缺血及缺血再灌注心肌损伤的保护作用

采用异丙肾上腺素致小鼠常压缺氧模型、垂体后叶素致大鼠急性心肌缺血模型及大鼠心肌缺血再灌注模型 ,考察薤白提取物抗心肌缺氧缺血及缺血后再灌注损伤的保护作用。结果表明薤白提取物能延长异丙肾上腺素作用的小鼠常压缺氧存活时间 ,对抗垂体后叶素所致的大鼠急性心肌缺血作用 ,并能明显保护缺血再灌注引起的大鼠心肌的损伤     

芍药苷对脑缺氧和缺血再灌注损伤的改善作用研究

目的探讨芍药苷对脑缺氧和缺血再灌注损伤的改善作用。方法复制小鼠脑缺氧实验与大鼠脑缺血再灌注损伤动物模型，观察芍药苷对中枢神经系统缺氧的影响和对脑缺血再灌注自由基损伤的保护作用。结果芍药苷可显著提高亚硝酸钠中毒小鼠的生存时间，提高脑组织中SOD的含量，GSH-PX的活性，降低MDA的含量。结论芍药苷能增加脑的抗耐缺氧能力、保护大鼠脑自由基损伤。     

蝙蝠葛碱对实验小鼠脑缺血的保护作用

目的　研究蝙蝠葛碱 (dauricine,Dau)对小鼠缺氧及急性脑缺血再灌注所致氧化损伤及能量代谢障碍的保护作用。方法　通过常压密闭缺氧实验观察Dau对小鼠缺氧情况下存活时间的影响 ;采用酶标仪及分光光度法测定小鼠急性脑缺血再灌注后脑皮层组织和线粒体氧化损伤指标及能量代谢指标活性或含量变化。结果　①Dau延长小鼠缺氧后存活时间。②Dau改善脑缺血再灌注损伤所致脑皮层组织及线粒体SOD活性下降、MDA含量升高及线粒体GSH Px活性下降 ;改善脑皮层组织LDH及线粒体ATPase活性下降。结论　①Dau对小鼠急性缺氧具有保护作用。②Dau对脑缺血再灌注所致脑皮层组织及神经细胞线粒体氧化损伤及能量代谢障碍具保护作用     

黄蜀葵总黄酮对全脑缺血损伤的保护作用

目的　研究黄蜀葵总黄酮 (TFA)对脑缺血及再灌注损伤的保护作用。方法　结扎双侧颈总动脉建立小鼠脑缺血模型 ,观察小鼠 6h存活率 ,测定缺血脑组织中丙二醛(MDA)含量 ;采用小鼠氮气缺氧模型 ,观察小鼠存活时间 ;采用结扎双侧颈总动脉合并血压下降法建立兔脑缺血再灌注模型 ,兔脑缺血 60min后再灌注 3 0min ,记录脑缺血和再灌注的脑电图 (EEG) ,测定缺血脑组织的丙二醛 (MDA)、乳酸脱氢酶 (LDH)。结果　TFA(3 0、60、12 0mg·kg-1)延长小鼠缺氧后的存活时间和提高脑缺血后小鼠的存活率及能抑制脑组织中MDA的增高。TFA(12、2 4、48mg·kg-1)抑制兔脑缺血再灌注损伤所致的EEG、MDA、LDH变化。结论　TFA对脑缺血及再灌注损伤有保护作用 ,其机制可能与抗自由基和脂质过氧化有关     

脉络宁口服液的抗脑缺血作用

目的　观察脉络宁口服液的抗脑缺血作用。方法　结扎大鼠两侧颈总动脉 ,制备急性不完全性脑缺血模型 ;采用麻醉犬在体实验法 ,观察药物对脑循环的影响。结果　口服液对大鼠急性不完全性脑缺血所致的脑血管通透性增加和脑水肿均有一定改善作用。口服液还能降低麻醉犬脑血管阻力 ,增加脑血流量。结论　脉络宁口服液有抗脑缺血作用 ,这一作用与其增加脑循环有关 ,与注射液相比 ,此作用较为缓慢、持久     

脉络宁口服液的抗脑缺血作用

目的 观察脉络宁口服液的抗脑缺血作用。方法 结扎大鼠两侧颈总动脉，制备急性不完全性脑缺血模型；采用麻醉犬在体实验法，观察药物对脑循环的影响。结果 口服液对大鼠急性不完全性脑缺血所致的脑血管通透性增加和脑水肿均有一定改善作用。口服液还能降低麻醉犬脑血管阻力，增加脑血流量。结论 脉络宁口服液有抗脑缺血作用，这一作用与其增加脑循环有关，与注射液相比，此作用较为缓慢、持久。     

西红花酸对小鼠缺氧损伤的保护作用

目的:研究西红花酸对小鼠缺氧损伤的保护作用。方法:观察不同缺氧模型小鼠的存活时间或存活率,测定大鼠局灶性脑缺血再灌注后血氧分压及血红蛋白含量。结果:西红花酸50和100 mg·kg~(-1)能显著延长常压缺氧、sc异丙肾上腺素、ip亚硝酸钠小鼠的存活时间及断头小鼠的张口喘气时间、提高双侧颈总动脉结扎小鼠30 min内的存活率;明显提高脑缺血再灌注大鼠血氧分压,而对血红蛋白含量无影响。结论:西红花酸能够提高小鼠耐缺氧能力,其作用可能与增加血氧分压有关。     

葛根总黄酮对糖尿病合并脑缺血再灌注小鼠的影响

目的观察葛根总黄酮（PLIS）对小鼠糖尿病性脑缺血再灌注模型脑能量代谢及脑组织的影响。方法采用四氧嘧啶复制小鼠糖尿病模型;用直径约为0．3mm的针灸针与CCAs血管一起结扎,20min后抽出针灸针的方法复制出脑缺血再灌注模型;通过测定该模型小鼠脑组织中钠钾ATP酶、钙镁ATP酶、LD、LDH的值,测定小鼠脑水肿及观察组织病理学的情况,探讨PLIS对小鼠糖尿病合并脑缺血再灌注模型脑能量代谢及脑组织的影响。结果PLIS可显著提高钠钾ATP酶、钙镁ATP酶活性,降低LD、LDH水平,降低脑含水量,对模型所致神经细胞和胶质细胞损伤有显著的拮抗作用和增强细胞耐缺氧作用。结论PLIS有改善糖尿病性脑缺血小鼠模型脑能量代谢及脑水肿情况,明显改善脑组织的病理情况,有保护脑缺血再灌注损伤作用。     

新型神经保护剂TQ0701-2对大鼠脑缺血再灌注损伤的保护作用

目的：研究新型神经保护剂TQ0701-2对大鼠脑缺血再灌注损伤的保护作用。方法：将120只雄性SD大鼠随机分为假手术组、模型组、依达拉奉组（3.0mg/kg）以及TQ0701-2高剂量组（6.0mg/kg）、中剂量组（3.0mg/kg）、低剂量组（1.5mg/kg）。假手术组仅进行手术而不造成缺血状态,其余各组均采用Longa线栓法制备大鼠MCAO模型,在缺血2h后进行再灌注。TQ0701-2三个剂量组和依达拉奉组分别在缺血前30min以及再灌注0、2h尾静脉注射TQ0701-2和依达拉奉,假手术组和模型组则给予等量的生理盐水。再灌注24h后观察大鼠神经功能损伤症状、脑组织梗死率以及病理组织学的改变。结果：模型组大鼠神经功能损伤严重,脑组织梗死率也明显增高（P〈0.01vs假手术组）。与依达拉奉的保护作用相同,TQ0701-2高中低三个剂量均能显著降低MCAO大鼠的神经功能评分和脑组织梗死率（P〈0.01vs模型组）,并且三个剂量的改善作用是随着浓度增大而增强的,具有剂量相关性。另外,TQ0701-2对大鼠脑缺血再灌注所致的神经元变性、坏死也有一定的保护作用。结论：研究表明,依达拉奉衍生物TQ0701-2对大鼠的脑缺血再灌注损伤有明显的神经保护作用。     

苦碟子注射液对大鼠急性脑缺血-再灌注损伤的保护作用

目的观察苦碟子注射液对脑缺血-再灌注损伤的保护作用并探讨其可能机制。方法用线栓法制作大鼠大脑中动脉栓塞模型(MCAO)。大鼠随机分成假手术组(sham)、脑缺血-再灌注损伤组(I/R)和苦碟子保护组(KD)。观察神经功能学评分,形态学观察(光镜和电镜),如脑梗塞面积(HE染色)及测定脑组织丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性。结果苦碟子注射液可降低缺血-再灌注损伤后的神经功能学评分、脑梗死面积、缺血脑组织丙二醛含量,减轻形态结构损伤,提高超氧化物歧化酶活性。结论苦碟子注射液对于脑缺血-再灌注损伤有一定的保护作用,其作用机制与清除氧自由基和抗脂质过氧化有关。     

Systemic administration of Zn2+ during the reperfusion phase of transient cerebral ischaemia protects rat hippocampus against iron-catalysed postischaemic injury

1. The aim of the present study was to test the protective role of intravenous Zn(2+) against iron-catalysed reperfusion injury in the hippocampus of ischaemic rats. 2. One hundred adult male Wistar albino rats were randomly divided into five groups. Rats in the first group were subjected to surgery (sham operation) without induction of cerebral ischaemia and injected with normal saline (i.v.). The second group of sham-operated rats were injected with 6 mg/kg, i.v., ZnCl(2). In the third group, rats were subjected to cerebral ischaemia for 60 min. Animals in the fourth group were subjected to cerebral ischaemia for 60 min followed by 8 h reperfusion. In the fifth group, rats were subjected to cerebral ischaemia for 60 min, followed by 8 h reperfusion with injection of a single dose of ZnCl(2) (6 mg/kg, i.v.) during the first 5 min of the reperfusion period. After reperfusion, animals were killed, their brains were dissected out on ice and the two hippocampi from each animal were isolated and analysed. 3. Cerebral ischaemia induced an increase in the iron content, lipidic peroxidation, apoptosis and metallothionein (MT) in the hippocampus. These effects were significantly increased in the hippocampus of ischaemic rats subjected to 8 h reperfusion compared with ischaemic non-reperfused rats. Intravenous administration of ZnCl(2)decreased the accumulation of iron, lipidic peroxidation and apoptosis produced by reperfusion, but increased the level of MT. 4. Data from the present study suggest that, after 1 h ischaemia, there is an increase in the permeability of the blood-brain barrier and this allows penetration of i.v. injected ZnCl(2), which can induce expression of brain MT, increase the anti-oxidant capacity and diminish iron-catalysed lipid peroxidation and apoptosis. This may give new insights as to how to improve the outcome for stroke patients.     

Antagonistic effects of ultra-low-molecular-weight heparin against cerebral ischemia/reperfusion injury in rats.

Heparin and low-molecular-weight heparin have long been proposed for stroke treatment. This study was conducted to demonstrate the antagonistic effects of ultra-low-molecular-weight heparin (ULMWH) on cerebral ischemic injury in rats and the mechanisms underlying the effects. Male Wistar rats were subjected to middle cerebral artery occlusion (MCAO) for 2h followed by reperfusion for 24h. ULMWH (0.5, 1 mg kg(-1), i.v.) was administered after the MCAO and reperfusion. Twenty-four hours after the reperfusion, neurological deficit scores, body weight and infarct volume were assessed. Spectrophotometric assay was used to determine the activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) of the brain. Furthermore, the intracellular Ca(2+) concentration ([Ca(2+)]i) was measured. The results showed that vein injection of ULMWH at doses of 0.5 and 1.0 mg kg(-1) exerted significant neuroprotective effects on rats with focal cerebral ischemic injury via significantly decreasing neurological deficit scores, increasing body weight, reducing the infarct volume. At the same time, ULMWH significantly decreased MDA content, and increased SOD activity in ischemic brain. Compared with model group, ULMWH decreased the intracellular calcium concentration remarkably. All these findings suggest that ultra-low-molecular-weight heparin might act as a neuroprotective agent useful in the treatment in focal cerebral ischemia.     

Evaluation of Withania somnifera in a middle cerebral artery occlusion model of stroke in rats

1. Stroke causes brain injury in millions of people worldwide each year. Despite the enormity of the problem, there is currently no approved therapy that can reduce infarct size or neurological disability. One of the approaches that can be used in limiting the neurological damage after stroke is the use of prophylactic treatment in patients with a high-risk of stroke. The present study was undertaken to investigate the effect of the Indian herbal plant Withania somnifera as a prophylactic treatment in the middle cerebral artery (MCA) occlusion model of stroke in rats. 2. Two groups of male Wistar rats were pretreated with a hydroalcoholic extract of W. somnifera (1 g/kg, p.o.) for 15 and 30 days. Thereafter, rats were subjected to focal ischaemia by occlusion of the MCA using an intraluminal thread. After 2 h MCA occlusion, reperfusion was allowed by retracting the thread. Animals were assessed for ischaemic changes using diffusion-weighted imaging 30 min after reperfusion. Twenty-four hours later, rats were subjected to motor performance tests and were subsequently killed for the estimation of the marker of oxidative stress malondialdehyde (MDA). The control group received vehicle and a similar protocol was followed. 3. Significant motor impairment, with elevated levels of MDA, was observed in vehicle-treated MCA-occluded rats. In addition, diffusion-weighted imaging showed increased signal intensity in the right hemisphere compared with the contralateral hemisphere. Treatment with W. somnifera for 15 days did not improve motor performance or decrease the elevated levels of MDA. However, when the pretreatment time of W. somnifera was increased to 30 days, it prevented motor impairment and significantly decreased the raised levels of MDA compared with vehicle-treated rats. In the W. somnifera (30 days)-pretreated group, the percentage hemispheric lesion area in diffusion-weighted imaging was significantly attenuated (17 +/- 2%) compared with the vehicle-treated MCA-occluded group (30 +/- 4%). 4. Because W. somnifera has been documented to have anti-oxidant properties, the protection afforded by W. somnifera could be due to its anti-oxidant effect. The present study provides first evidence of the effectiveness of an Indian herb in focal ischaemia.     

胡黄连苷Ⅱ对大鼠脑缺血/再灌注损伤Caspase-3和PARP表达的影响

目的探讨胡黄连苷Ⅱ(picrodideⅡ)对大鼠脑缺血/再灌注损伤脑组织半胱天冬酶-3(Caspase-3)和多聚腺苷酸二磷酸核糖聚合酶(PARP)表达的影响。方法线栓法建立大鼠大脑中动脉闭塞/再灌注模型;经尾静脉注射胡黄连苷Ⅱ(10mg·kg-1)和丹参素钠(10mg·kg-1)干预治疗,Bed-erson法评价动物神经行为功能,氯化三苯基四氮唑(TTC)染色观察脑梗死体积,苏木精伊红(HE)染色观察脑组织结构,原位末端标记(TUNEL)法检测神经细胞凋亡,免疫组化和酶联免疫法检测Caspase-3和PARP表达。结果脑缺血2h/再灌注22h后,大鼠出现神经行为功能障碍,缺血侧半球出现梗死病灶,脑组织Caspase-3和PARP表达增强,细胞凋亡数较假手术组明显增多(P<0.05)。胡黄连苷组和丹参素钠组大鼠Bederson′s评分和脑梗死体积,Caspase-3和PARP表达以及细胞凋亡数量较阴性对照组均降低(P<0.05)。但胡黄连苷组与丹参素钠组比较,各项指标均差异无显著性(P>0.05)。结论胡黄连苷Ⅱ可能通过下调Caspase-3和PARP表达,抑制脑缺血/再灌注损伤诱导的细胞凋亡,从而改善动物的神经行为功能。     

COX-2抑制剂对大鼠局灶性脑缺血再灌注损伤的保护作用研究

目的观察选择性环氧合酶2(cyclooxygenase2,COX2)抑制剂尼美舒利(nimesulide)对大鼠局灶性脑缺血/再灌注损伤后神经功能缺陷、脑梗死体积及前列腺素E2(PGE2)含量的影响。方法用线栓法制作大鼠脑缺血/再灌注损伤模型,动物分别于缺血前30min、再灌注后6h、12h给予3个不同剂量尼美舒利(3、6和12mg/kg,ip)或等体积的溶媒。于再灌注后6、12、24h进行神经功能评分;采用TTC染色法测定脑梗死体积;应用ELISA法检测PGE2含量。结果尼美舒利呈剂量依赖性减少脑梗死体积并改善功能预后,与溶媒组比较有显著性差异;各尼美舒利治疗组脑梗死后PGE2含量和溶媒组相比显著降低。结论尼美舒利对缺血性脑损伤具有明显的保护作用,其保护作用可能与通过减少花生四烯酸环氧酶途径的代谢产物,从而抑制脑缺血后的炎症反应有关。     

缺血预处理对大鼠局灶性脑缺血再灌注损伤的影响

目的:探讨缺血预处理对大鼠局灶性脑缺血再灌注损伤的的保护作用。方法:SD大鼠60只,随机分为假手术组、模型组、预处理组。建立大鼠局灶性(MCAO)脑缺血再灌注损伤模型,预处理组24h前先行20min的缺血预处理,再缺血2h再灌注24h;假手术组不阻断血流,模型组未做缺血预处理。比较各组的神经功能评分、脑匀浆LDH、CK及MAD含量。结果:模型组神经功能障碍高于预处理组(P<0.01),模型组和预处理组大鼠脑缺血再灌注后脑匀浆LDH、CK明显低于假手术组(P<0.01),脑匀浆MAD明显高于假手术组(P<0.01),模型组大鼠脑缺血再灌注后脑匀浆LDH、CK明显低于预处理组(P<0.05),模型组大鼠脑缺血再灌注后脑匀浆MAD明显高于预处理组(P<0.05)。结论:缺血预处理对模型局灶性脑缺血再灌注损伤具有保护作用。     

颈内动脉注射藻蓝蛋白对大鼠急性脑缺血再灌注损伤的保护作用

目的 探讨经颈内动脉微量注射藻蓝蛋白对脑缺血再灌注损伤神经的保护作用.方法 成年健康雄性Wistar大鼠84只,线检法建立大脑中动脉阻塞再灌注(MCAO/R)模型,经颈内动脉微量注射藻蓝蛋白进行治疗,观察不同剂量藻蓝蛋白对动物神经功能评分、脑组织含水量、脑梗死体积、神经细胞凋亡等指标的影响.结果 脑缺血再灌注损伤后,动物出现不同程度的神经行为功能障碍.藻蓝蛋白治疗后,动物神经功能评分明显改善,脑组织含水量显著降低,脑梗死体积显著减小,皮质、纹状体和海马区神经细胞凋亡明显减少.结论 经颈内动脉微量注射藻蓝蛋白对急性脑缺血再灌注损伤有一定的保护作用.     

Neuroprotective potentials of candesartan,atorvastatin and their combination against stroke induced motor dysfunction

Cerebral ischaemia is a leading cause of death and disability. The objective of the present investigation was to explore the neuroprotective potentials of candesartan and atorvastatin alone and their combination against the cerebral ischaemia induced behavioral, biochemical, and mitochondrial dysfunction. Male Wistar rats (200–220 g) were subjected to bilateral common carotid artery occlusion for 30 min followed by 24 h reperfusion. Candesartan (0.1 and 0.3 mg/kg) and atorvastatin (10 and 20 mg/kg) were pretreated for 7 days before animals were subjected to ischaemia reperfusion injury. Various behavioral tests (locomotor activity and rotarod performance), biochemical parameters (Malondialdehyde levels, nitrite concentration, superoxide dismutase and catalase activity, redox ratio, and GST) and mitochondrial enzyme (Complex I, II, III, and IV) dysfunctions were measured in cerebral cortex, striatum and hippocampus of the ischaemic brain. Seven days candesartan (0.1 and 0.3 mg/kg) or atorvastatin (10 and 20 mg/kg) pretreatment significantly attenuated neurobehavioral alterations, oxidative damage and restored mitochondrial enzyme dysfunction as compared to control (I/R) group. Further, combined treatment of candesartan (0.1 mg/kg) and atorvastatin (10 mg/kg) significantly potentiated their protective effect which was significant as compared to their effect alone. Present study suggests the protective effect of candesartan and atorvastatin and their combination against ischaemia reperfusion induced behavioral and biochemical alterations in rats.