甲磺酸桂哌齐特对缺血再灌注脑损伤大鼠的保护作用

目的:观察甲磺酸桂哌齐特对大鼠缺血性脑损伤保护作用?方法:线拴法建立大鼠大脑中动脉阻塞(MCAO)再灌注损伤模型,72只雄性SD大鼠随机分为6组:假手术组?模型组?甲磺酸桂哌齐特组(20?40?80 mg/kg)和马来酸桂哌齐特组,观察药物对脑缺血再灌注大鼠的血栓形成?血小板聚集?脑梗死体积和对脑组织病理形态学变化的影响?结果:与模型组比较,甲磺酸桂哌齐特(40?80 mg/kg)可减少缺血再灌后脑梗死体积,抑制血栓形成和血小板聚集(P < 0.05);同时可减轻脑组织神经元核固缩?溶解和脑细胞肿胀?与马来酸桂哌齐特相比无明显差异?结论:甲磺酸桂哌齐特对局灶性脑缺血再灌注损伤有保护作用?     

银杏叶注射液对实验性大鼠局灶性脑缺血的保护作用

以行为障碍、脑梗死范围、脑含水量、脑组织病理改变为观察指标,研究银杏叶注射液（ＧＢＥ）对大鼠大脑中动脉闭塞所致局部脑缺血的防治作用。结果表明,ＧＢＥ２０、４０ｍｇ／ｋｇ静脉注射可显著降低大鼠脑梗死范围和脑含水量,改善行为障碍。脑组织形态学检查显示,ＧＢＥ４０ｍｇ／ｋｇ组动物脑组织缺血病变较轻。提示ＧＢＥ对局灶性脑缺血具有保护作用。     

Attenuation of Brain Inflammatory Response after Focal Cerebral Ischemia/Reperfusion with Xuesaitong Injection(血塞通注射液) in Rats

Objective： To investigate the neuro-protective effect of Xuesaitong Injection （血塞通注射液, XST） on brain inflammatory response after transient focal cerebral ischemia/reperfusion in rats. Methods： Focal cerebral ischemia/reperfusion models of male rats were induced by transient occlusion for 2 h of middle cerebral artery （MCA） which was followed by 24 h reperfusion. XST was administered through intraperitoneal injection of 25 mg/kg or 50 mg/kg at 4 h after the onset of ischemia. After reperfusion for 24 h, the neurological function score was evaluated, the brain edema was detected with dry-wet weight method, the myeloperoxidase （MPO） activity and the expression of intercellular adhesion molecule-1 （IOAM-l） of ischemic cerebral cortex and caudate putamen was determined by spectrophotometry and immunohistochemistry respectively. Results： XST not only lowered neurological function score at the dose of 50 mg/kg, but reduced brain edema and inhibited MPO activity and IOAM-1 expression as compared with the ischemia/reperfusion model group （P〈0.01）. Conclusion： XST has a definite effect on inhibiting the expression of IOAM-1 and neutrophil infiltration in rats with cerebral ischemia/reperfusion when treatment started at 4 h after ischemia onset, and also attenuates inflammation in the infarcted cerebral area.     

局灶性脑缺血再灌注时诱导型一氧化氮合酶在大鼠脑组织的分布特点

目的观察大鼠脑缺血再灌注时诱导型一氧化氮合酶（inducible nitric oxide synthase,iNOS）在脑组织的分布特点,及其在缺血性脑损伤中的作用。方法阻断大鼠大脑中动脉（middle cerebral artery,MCA）血流2h。再灌注3-120h制成脑缺血再灌注模型。苏木精-伊红染色评价缺血性脑损伤的组织学特点,免疫组织化学（immunohistochemistry,IHC）染色观察iNOS在脑组织的分布特点。结果再灌注12h组开始出现神经元不可逆变性,24h梗死形成。正常组和假手术组、再灌注3h组无iNOS阳性的细胞。再灌注12～120h过程中,脑组织iNOS阳性细胞在再灌注12h开始表达,24h达到高峰,后逐渐下降。再灌注12～120h各组与正常组、假手术组、3h组比较P〈0．01。再灌注各组与24h组比较P〈0．01。结论iNOS在脑缺血再灌注后12h开始表达,24h达高峰,后逐渐下降,其细胞定位以小胶质细胞为主。iNOS与脑缺血再灌注后期神经元损伤有明显关联。为临床早期使用iNOS抑制剂减少脑损害,提供了一定的参考价值。     

实验性脑缺血原癌基因表达与神经元凋亡/坏死关系的研究

目的 研究局灶脑缺血／再灌注Wistar大鼠原癌基因c-fos、c-jun表达在缺血性脑损害中可能的作用机制。方法 采用线栓法制备大鼠局灶脑缺血／再灌注模型，于缺血1.5h再灌注4h、24h、72h观察c-fos、c-jun表达及神经元坏死、调亡的变化规律。结果 再灌注4h c-fos、 c-jun及神经元调亡明显升高（P＜0.01），c-fos和c-jun阳性蛋白表达在4h达高峰（P＜0.01），随后在再灌注各时相点无显著性差异（P＞0.05）。结论 c-fos和c-jun异常表达与神经元坏死、凋亡密切相关。     

尼莫地平对脑缺血再灌注后大鼠血脑屏障通透性的影响

目的 研究尼莫地平对脑缺血再灌注后大鼠离屏障（ＢＢＢ）通透性的影响。方法 采用线栓法制作大鼠大脑中动脉闭塞的局灶性脑缺血模型。缺血１ｈ后再灌注,分别于血前及再灌注后静脉注射尼莫地平。采用免疫组织化学ＳＡＢＣ法,观察再灌注１２ｈ时,内生免疫球收Ｇ（ＩｇＧ）在脑组织中的表达,比较缺血前注射尼莫地平组,未注射尼莫地平组及再灌注后注射尼莫地平组三组大鼠脑组织中ＩｇＧ的表达水平,结果 未注射尼莫地平组大鼠,     

人参总皂苷对大鼠脑缺血再灌注的神经保护研究

目的:了解人参总皂苷对MCAO再灌注大鼠的神经保护作用。方法:采用神经行为学评分,Nissl染色法了解人参总皂苷的抗缺血损伤作用。结果:总皂甙20mg/kg和60mg/kg治疗组可改善缺血再灌注后24h神经行为学评分,以20mg/kg效果更为显著。总皂甙20mg/kg和60mg/kg治疗组大鼠顶叶皮层缺血半暗带区神经元存活较多,其中以20mg/kg组神经元存活率最高。结论:人参总皂苷对MCAO后再灌注的大鼠脑组织具有保护作用。     

基于细胞能量代谢的仙鹤草不同提取物抗脑缺血再灌注损伤作用机制的实验研究

目的探讨仙鹤草抗脑缺血再灌注损伤的作用机制,筛选有效部位。方法采用改良MCAO法制备脑缺血再灌注损伤模型,将SD大鼠随机分为假手术组、模型组、仙鹤草乙酸乙酯提取物组(4 g/kg)、仙鹤草乙醇提取物组(4 g/kg)、仙鹤草水提取物组(4 g/kg)、尼莫地平组(0.5 mg/kg)。分别于再灌注0、6 h分组灌胃给药,观察各组对脑缺血再灌注引起的神经功能缺损症状、脑梗死体积及脑组织病理学(透射电镜)的调控作用,以及对脑组织中超氧化物歧化酶(SOD)、丙二醛(MDA)、一氧化氮(NO)的调控作用,探讨其抗脑缺血再灌注损伤的作用机制,筛选不同提取物中的有效部位。结果仙鹤草水提取物能明显减轻大鼠的神经功能缺损症状(P0.05);通过TTC染色及电镜观察,仙鹤草水提取物能明显缩小脑梗死体积(P0.01)及改善大鼠大脑皮质神经元病变,提高大鼠脑缺血再灌后SOD,显著降低MDA含量和NO水平(P0.05)。结论仙鹤草水提取物可能成为抗脑缺血再灌注损伤有效部位,其作用机制可能为抑制脂质过氧化反应、增加缺血区脑组织能量物质含量,最终达到防止脑组织细胞损伤的作用。     

大鼠局灶性脑缺血再灌注后神经细胞凋亡和Bcl-2蛋白表达的改变及银杏叶提取物的保护作用

目的研究大鼠局灶性脑缺血再灌注后神经细胞凋亡和Bcl-2蛋白表达的变化及银杏叶提取物对其表达的影响.方法制造大鼠大脑中动脉缺血再灌注模型.40只Wistar雄性大鼠被随机分为A假手术组、B缺血组、C小剂量治疗组和D大剂量治疗组.于术前30min及术后1 h分别给予银杏叶提取物20mg/kg和40mg/kg腹腔内注射.应用TTC染色及HE染色观察梗死体积及缺血坏死程度,应用免疫组化染色及POD法检测Bcl-2蛋白表达及凋亡细胞数.结果C、D两组梗死体积明显小于B组(P＜0.01),D组梗死体积小于C组(P＜0.05);C、D两组凋亡细胞数明显少于B组(P＜0.01),D组凋亡细胞数少于C组(P＜0.05);C、D两组Bcl-2蛋白表达明显高于B组(P＜0.01),D组Bcl-2蛋白表达高于C组(P＜0.05).结论银杏叶提取物可通过上调Bcl-2蛋白表达,减少神经细胞凋亡,对脑缺血再灌注损伤起保护作用,疗效与剂量有关.     

丁苯酞预处理对缺血再灌注大脑神经元及血脑屏障的影响

目的 探讨丁苯酞（NBP）对缺血再灌注大脑神经元和血脑屏障影响。方法 SD 大鼠 30 只随机分为假手术组、缺血 再灌注组、NBP 20 mg/kg 组、NBP 40 mg/kg 组、NBP 80 mg/kg 组,术前 1 周灌胃给不同剂量 NBP,共 7 d。线栓法制作大 脑中动脉缺血再灌注模型,术后进行神经行为学评分,检测大脑组织中伊文思蓝的含量和血脑屏障通透性变化,透射电 镜观察缺血区脑组织神经元和血脑屏障的超微结构变化。结果 与缺血再灌注组比较,NBP 各组神经功能缺损评分明显降 低（P<0.01,P<0.05）,脑组织中伊文思蓝的含量减少（P<0.01,P<0.05）,血脑屏障的通透性降低,神经元和血脑屏障 超微结构损伤明显减轻。结论 丁苯酞预处理对脑缺血再灌注损伤神经元和血脑屏障具有预防保护作用     

Combination Therapy with LXW7 and Ceria Nanoparticles Protects against Acute Cerebral Ischemia/Reperfusion Injury in Rats

Ischemia/reperfusion is known to greatly increase oxidative stress in the penumbra, which results in brain damage. Integrin αvβ3 is selectively up-regulated with ischemic injury to the brain and remains elevated throughout reperfusion. We determined whether or not a new compound biotinylated-LXW7-ceria nanoparticle (CeNP) (bLXW7-CeNP) plays a role in brain protection in the rat model of middle cerebral artery occlusion/reperfusion and shows better effects than CeNPs alone in improving the outcomes of focal oxidative stress and apoptosis more effectively. Male Sprague-Dawley rats were subjected to focal cerebral ischemia for 2 h followed by a 24-h reperfusion. Drug treatment was intravenously administered via the caudal vein 1 h after occlusion. Rats were randomly divided into the following 4 groups: bLXW7-CeNP treatment group (0.5 mg/kg); CeNP treatment group (0.5 mg/kg); control saline group; and sham group. Brains were harvested 24 h after reperfusion, and the neurologic deficit scores, infarction volume, blood-brain barrier (BBB) disruption, and the level of oxidative stress and apoptosis were determined. Results showed that the bLXW7-CeNP and CeNP treatments could improve neurologic deficit scores, infarction volume, BBB disruption, and the level of oxidative stress and apoptosis. Compound bLXW7-CeNP treatment exhibited better effects than CeNp treatment and showed remarkable statistical differences in the infarction volume, the degree of BBB breakdown, the apoptosis and oxidative stress, apart from neurologic deficit scores. Thus, we concluded that bLXW7-CeNP protects against acute cerebral ischemia/reperfusion injury. BLXW7, as a ligand of integrin αvβ3, may be able to effectively localize the anti-oxidant CeNPs to the ischemic penumbra region, which may provide more adequate opportunities for CeNPs to exert anti-oxidative stress effects and subsequently reduce apoptosis in acute cerebral ischemia/reperfusion.     

甘草总黄酮对脑缺血后神经元特异性烯醇化酶和一氧化氮的影响

目的研究甘草总黄酮对大鼠局灶脑缺血的作用。方法采用线栓法建立大鼠大脑右侧中动脉(MCA)缺血再灌注模型,并用三种不同剂量的甘草总黄酮灌服。测定缺血2小时再灌注24小时时神经功能缺失评分、血清和脑组织中一氧化氮(NO)、血清神经元特异性烯醇化酶(NSE)含量及观察病理组织学变化。结果甘草总黄酮能促进大鼠MCA缺血再灌注24小时后神经功能恢复,减轻脑水肿,减少神经元脱失,能明显降低血清、脑组织中NO含量,能显著降低血清NSE。结论甘草总黄酮能减轻缺血性脑损害,保护脑组织。     

马尾松松针提取物调节JNK3/caspase-3信号转导减轻大鼠脑缺血再灌注后氧化应激损伤

目的：探讨马尾松松针提取物（PNE）对大鼠脑缺血再灌注后氧化应激损伤的保护作用。方法：将SD雄性大鼠随机分为手术对照组、模型对照组、依达拉奉组、PNE小剂量组（200 mg/kg）、PNE中剂量组（400 mg/kg）、PNE大剂量组（800 mg/kg）,于造模前连续7 d及造模后6 h分别灌胃给药。其中,手术对照组和模型对照组灌胃给予等渗氯化钠溶液,依达拉奉组灌胃给予等渗氯化钠溶液的同时腹腔注射依达拉奉3 mg/kg,PNE各组灌胃给予各剂量PNE。通过大脑中动脉阻塞法建立脑缺血再灌注损伤大鼠模型,于再灌注24 h后测定各组大鼠神经功能缺损评分、脑组织含水量、脑梗死体积。采用苏木素-伊红染色观察大脑皮层及海马组织结构病理变化并统计正常神经细胞数;TUNEL法检测大脑皮层神经细胞凋亡率;试剂盒检测缺血侧脑组织一氧化氮、丙二醛含量与超氧化物歧化酶（SOD）活性;蛋白质印迹法检测大脑皮层c-Jun氨基末端激酶（JNK）3、磷酸化JNK3、B淋巴细胞瘤蛋白（Bcl）-2、Bcl-2相关X蛋白（Bax）、细胞色素C、胱天蛋白酶（caspase）-3的蛋白表达水平。结果：与模型对照组比较,PN...     

The Protective Effect of Rosuvastatin on Ischemic-Brain Injury and Its Mechanism

The statins, which lower plasma cholesterol levels, are 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase inhibitors. To date, stains have developed to third generation, which include five commonly used stains: lovastatin, pravastatin, simvastatin, fluvastatin and atorvastatin. Recently, a new statin, named rosuvas-tatin, was used in the third stage of clinical trial. Rosu-vastatin, in contrast to most other statins, has the more powerful capability to lower plasma cholesterol levels,…     

必存对脑缺血再灌注损伤的保护作用

目的 探讨有效治疗急性脑缺血再灌注损伤的新药物。方法采用线栓法制备大鼠大脑中动脉再灌注模型。将必存溶于生理盐水，在建立模型后1h，6h或24h注入大鼠股静脉中，1星期后分别断头取大鼠脑组织作病理切片并计算梗死体积。结果对照组，0．5mg必存治疗组，1mg必存治疗组，坏死体积依次明显减少。结论必存对脑缺血再灌注损伤组织有明显的保护作用。     

大黄酚对局灶性脑缺血再灌注小鼠Beclin1及Bax的作用

目的 研究大黄酚（chrysophanol,CHR）对短暂性局灶性脑缺血再灌注小鼠缺血半暗带区自噬蛋白Beclin1及缺血侧大脑半球促凋亡蛋白Bax水平的影响,探究CHR对脑缺血再灌注损伤的保护机制。方法 将18只健康C57BL/B6雄性小鼠按数字表法随机分为3组：假手术（Sham）组、大脑中动脉梗死（middle cerebral artery occlusion,MCAO）组、CHR组（自造模当天至再灌注后14 d每天按0.1 mg/kg腹腔注射CHR）,每组6只。按照线栓法制作小鼠右侧大脑中动脉缺血45 min再灌注模型。再灌注14 d时将小鼠处死后,迅速断头、取脑,应用免疫荧光染色法检测脑组织冰冻切片缺血半暗带区自噬Beclin1水平,Western blotting法检测缺血侧脑组织Bax蛋白水平。结果 1） Sham组小鼠脑内偶见Beclin1阳性细胞。MCAO组小鼠脑缺血半暗带区Beclin1表达水平比Sham组显著升高（P<0.05）。给予CHR治疗的脑缺血再灌注小鼠半暗带区Beclin1的表达水平比MCAO组显著减少（P<0.05）。2）在脑缺血半暗带区,Beclin1与神经元标志物NeuN共定位。3） MCAO组小鼠缺血侧脑组织Bax蛋白水平比Sham组明显升高（P<0.05）。CHR组小鼠缺血侧脑组织Bax蛋白水平比MCAO组显著减少（P<0.05）。结论 CHR可能通过抑制Bax蛋白表达水平,减少Beclin1蛋白产生,减轻神经元凋亡,避免自噬过度激活,从而对脑缺血再灌注损伤发挥长期神经保护作用。     

Therapeutic time window of flurbiprofen axetil’s neuroprotective effect in a rat model of transient focal cerebral ischemia

Background The neuroprotective effect of the cyclooxygenase （COX） inhibitor has been demonstrated in acute and chronic neurodegenerative processes. But its function under cerebral ischemic conditions is unclear. This study was designed to evaluate the neuroprotective efficacy of emulsified flurbiprofen axetil （FA, COX inhibitor） and its therapeutic time window in a model of transient middle cerebral artery occlusion （MCAO） in rats. Methods Forty-eight male SD rats were randomly assigned into six groups （n=8 in each group）; three FA groups, vehicle, sham and ischemia/reperfusion （I/R） groups. Three doses of FA （5, 10 or 20 mg/kg, intravenous infusion） were administered just after cerebral ischemia/reperfusion （I/R）. The degree of neurological outcome was measured by the neurologic deficit score （NDS） at 24, 48 and 72 hours after I/R. Mean brain infarct volume percentage （MBIVP） was determined with 2,3,5-triphenyltetrazolium chloride （TTC） staining at 72 hours after I/R. In three other groups （n=8 in each group）, the selected dosage of 10 mg/kg was administrated intravenously at 6, 12 and 24 hours after I/R. Results The three different doses of FA improved NDS at 24, 48 and 72 hours after I/R and significantly reduced MBIVP. However, the degree of MBIVP in the FA 20 mg/kg group differed from that in FA 10 mg/kg group. Of interest is the finding that the neuroprotective effect conferred by 10 mg/kg of FA was also observed when treatment was delayed until 12-24 hours after ischemia reperfusion. Conclusion COX inhibitor FA is a promising therapeutic strategy for cerebral ischemia and its therapeutic time window could last for 12-24 hours after cerebral ischemia reperfusion, which would help in lessening the initial ischemic brain damage.     

Protective action of phenytoin on cerebral ischemia in rats]

In order to study and modify the ischemic brain lesions, protecting the reversible damage of neurons, and limiting the ischemic damage both models of cerebral ischemia--focal cerebral ischemia induced by photochemically, and brain reperfusion after ligation of common carotid arteries bilateral in Wistar rats were used to investigate the protective effect of diphenylhydantoin (DPH) on cerebral ischemia. Two groups of rats received DPH 10 mg/kg and 30 mg/kg respectively were compared with those having received normal saline immediately after cerebral ischemia. The effects of DPH on the changes of EEG, biochemical marker and pathologic lesion in focal cerebral ischemia in rats were evaluated. The results showed that the degree of restoration of EEG in the group treated with DPH was better than in the group with normal saline, the content of water in ischemic cerebral tissue was decreased significantly (P < 0.05), the activity of Na-K-ATPase and antioxidant was increased significantly (P < 0.01, P < 0.05, respectively), and the percentage of necrotic neurons in periischemic area was decreased markedly (P < 0.001) in groups treated by DPH. The results suggest that there is a definite protective effect of DPH on cerebral ischemia.     

依达拉奉对脑缺血再灌注损伤的保护作用

目的:研究依达拉奉对急性脑缺血再灌注损伤的保护作用。方法:将108只SD大鼠分成生理盐水组和依达拉奉高剂量组(1 mg)及低剂量组(0.5 mg),每组再各分为1 h,6 h及24 h组,每组12只。采用线栓法制造大鼠大脑中动脉再灌注模型,将依达拉奉生理盐水溶液于造模后1,6,24 h注入大鼠股静脉中,1周后断头取脑,组织做病理切片并计算梗死体积。结果:依达拉奉高剂量组(1 mg)、依达拉奉低剂量组(0.5 mg)、对照组坏死体积依次明显减少。结论:依达拉奉对脑缺血再灌注损伤组织有明显保护作用。