白藜芦醇苷对大鼠脑缺血后运动功能恢复作用的研究
|
摘要
目的：观察白藜芦醇苷对大鼠局灶性脑缺血再灌注损伤后急性损伤及长期给药后运动功能康复的影响。并在此基础上探讨白藜芦醇苷的作用机制。体外培养PC12细胞,建立氧糖剥夺损伤模型(oxygen-glucose deprivation,OGD),观察白藜芦醇苷对细胞形态及细胞活力的影响。
方法：(1)采用栓线法制备大鼠急性局部脑缺血再灌注损伤模型(MCAO)。在剂量研究中,将大鼠随机分成7组：模型组、假手术组、阳性对照组、白藜芦醇苷各剂量组(5mg/kg、10mg/kg、20mg/kg、40mg/kg)。观察白藜芦醇苷对大鼠缺血大脑的梗塞面积及含水量的影响。(2)较长周期给药实验中,将大鼠随机分成6组：模型组、假手术组、阳性对照组、白藜芦醇苷高、中、低各剂量组,造模成功后第2、第4、第6、第8天,称量体重,分别采用姿势反射试验、肢体不对称试验两种方法作为行为学评价指标,观察白藜芦醇苷对大鼠缺血大脑的保护作用。(3)体外培养PC12细胞,应用化学方法建立细胞OGD损伤模型,观察细胞形态学改变,并且应用四甲基偶氮唑蓝法(methyl thiazolyl tetrazolium, MTT)观察不同浓度白藜芦醇苷对细胞活力的影响,测定细胞外液乳酸脱氢酶(Lactate dehydrogenase, LDH)浓度,一氧化氮(NO)及丙二醛(MDA)含量,超氧化物歧化酶(SOD)活性。
结果：(1)与大鼠模型组(28.30±7.92)比较,应用白藜芦醇苷后大鼠脑梗塞面积逐渐降低呈浓度依赖趋势分别为19.21±14.72、15.32±13.53、14.47±10.85、13.74±12.89。与大鼠模型组(65.81±1.75)比较,应用白藜芦醇苷后大鼠水肿程度逐渐降低呈浓度依赖趋势分别为64.27±1.45、63.91±1.53、63.68±1.80、63.57±1.65。白藜芦醇苷5mg/kg组有改善效果但无统计学意义。(2)较长周期给药后体重变化率及行为学评价结果显示：i体重变化率：假手术组除术后第1天体重下降,其余每天体重呈增长趋势。模型组由于缺血再灌注引起的损伤,造成体重呈下降趋势。(各时间点与给药前比较)体重变化率,与假手术组同时间点(1.26±8.40、4.44±6.84、7.22±6.18、10.80±5.81)比较,模型组造模后第2天、4天、6天和8天有显著性增加(-7.61±5.71、-10.57±10.49、-12.40±12.29、-12.05±13.52),有显著性差异(P＜0.01)。白藜芦醇苷低、中、高剂量组(5、10、20mg/kg)给药后可改善缺血再灌注引起的体重下降。同时间点体重变化率与模型组比较,中剂量组造模后第2天、4天和6天有显著性降低(-9.07±3.85、-9.44±11.97、-10.90±15.82),有显著性差异(P＜0.05)；高剂量组造模后第4天和6天有显著性降低(-12.15±12.80、-13.25±13.89),有显著性差异(P＜0.05)；阳性对照组给药可改善缺血再灌注引起的体重下降(-9.58±3.09、-9.12±6.56、-9.43±7.67、-7.50±8.46),且有显著性差异(P＜0.05)。ii姿势反射试验：造模后第2天、4天、6天和8天各时间点与假手术组(0±0)比较,模型组有显著性增加(1.42±0.48、1.36±0.33、1.29±0.51、0.91±0.30),具有显著性差异(P＜0.01)。白藜芦醇苷低、中、高剂量组(5、10、20mg/kg)给药后可改善缺血再灌注引起的肢体功能异常。与模型组比较,高剂量组能显著性降低缺血再灌注引起的肢体功能异常(1.01±0.37、0.78±0.42、0.77±0.28、0.59±0.39),具有显著性差异(P＜0.01)。与模型组比较,低、中剂量组在造模后第4天能显著性降低缺血再灌注引起的肢体功能异常(1.06±0.29、1.01±0.30),有显著性差异(P＜0.05)；阳性对照组给药可显著性降低缺血再灌注引起的肢体功能异常(1.08±0.31、0.78±0.31、0.87±0.63、0.64±0.44),且有显著性差异(P＜0.05)。iii肢体不对称试验：与假手术组(9.5±21.51、-0.75±25.77、4.25±23.64、4±24.42)比较,造模后第2天、4天、6天和8天各时间点模型组前肢不对称应用评分均显著升高(66.43±32.78、69.29±23.69、50.36±17.81、51.79±40.03),具有显著性差异(P＜0.05)。白藜芦醇苷低、中、高剂量组(5、10、20mg/kg)给药后可改善缺血再灌注引起的左前肢触及桶壁频率较少,右前肢触及桶壁频率较多。与模型组比较,高剂量组在造模后第2天、4天和6天能显著下降前肢不对称应用评分(35.67±34.69、29±27.33、28.33±27.82),具有显著性差异(P＜0.05)。与模型组比较,低、中剂量组在造模后第4天能显著下降前肢不对称应用评分(47.5±18.60、46.88±19.07),具有显著性差异(P＜0.05)；阳性对照组在造模后第2天、4天和6天能显著下降前肢不对称应用评分(26.56±29.98、44.38±28.57、33.13±27.5),且有显著性差异(P<0.05)。白藜芦醇苷能显著改善缺血引起的大鼠肢体活动障碍。(3)氧糖剥夺损伤后,PC12细胞形态发生了一定的改变,白藜芦醇苷12.5μM, 25μM,50μM三个剂量组显著降低了氧糖剥夺对PC12细胞成的损伤：PC12细胞的A值由模型的70.45±2.94增加到74.2±3.88、92.55±5.08、90.3±4.55；且有显著性差异(P<0.05)。与模型组705.85±30.65相比,应用白藜芦醇苷后PC12细胞各组细胞外液LDH活力(U/L)也逐渐降低呈浓度依赖趋势LDH分别为630.76±31.28、619.72±23.91、599.34±37.54,且有显著性差异(P＜0.05)。与模型组11.09±1.1相比,应用白藜芦醇苷后PC12细胞各组细胞外液MDA含量(nmol/mg)也逐渐降低呈浓度依赖趋势MDA分别为9.43±0.53、9.27±0.84、7.82±0.63，且有显著性差异(P＜0.05)。与模型组16.69±0.3相比,应用白藜芦醇苷后PC12细胞各组细胞外液SOD活性(U/mg)也逐渐增高呈浓度依赖趋势SOD分别17.67±0.23、18.79±0.26、18.68±0.15,且有显著性差异(P＜0.05)。与模型组42.25±0.92相比,应用白藜芦醇苷后PC12细胞各组细胞外液NO含量(μmol/g)也逐渐降低呈浓度依赖趋势NO分别为31.25±2.11、25.88±2.06、25.38±2.73,且有显著性差异(P＜0.05)。
结论：白藜芦醇苷对大鼠缺血大脑有保护作用,能明显减少大脑的梗塞面积和水肿程度,改善缺血引起的肢体行为障碍；离体细胞实验表明白藜芦醇苷对PC12细胞氧糖剥夺损伤具有保护作用。
Objective:To study the effect of resveratrol on the cerebral infarction and behavior in rats after focal cerebral ischemia-reperfusion injury. Based on this model, we also explore the possible mechanisms of the effect. Moreover, to investigate the effect of resveratrol on the viability and morphology of cell by establishing the oxygen-glucose deprivation (OGD) model in PC 12 cells.
Methods:(1)Rat model of focal cerebral ischemia reperfusion injury made by occlusion of middle cerebral artery was used. In the dose-dependence study, rats were randomly divided into 7 groups:model group, sham-operated group, positive control group, and resveratrol-treated groups (5mg/kg, 10mg/kg,20mg/kg and 40mg/kg). The size of cerebral infarction, the extent of edema and the water content were measured in the rats. (2)In the long-term experiment, the rats were randomly divided into 6 groups:model group, sham-operated group, positive control group, and resveratrol-treated groups of high, medium and low doses. Postural reflex test and limb use asymmetry test were performed as behavioral indexes on 2th,4th,6th and 8th day after the rats were subjected to focal cerebral ischemia-reperfusion injury for evaluating the protective effect of resveratrol on the brain damage. (3) By establishing oxygen-glucose deprivation (OGD) model of PC 12 cells in vitro, we observed the change of the cells. At the same time, MTT assay was applied to evaluate the cell's viability and biochemical method was used to determine LDH activity.the contents of nitric oxide(NO) and the malondialdehyde(MDA). the activity of superoxide dismutase(SOD).
Results:(1) Compared with model group(28.30±7.92), cerebral infarction area decreased obviously:19.21±14.72,15.32±13.53,14.47±10.85,13.74±12.89. Compared with model group(65.81±1.75),the extent of brain edema decreased obviously:64.27±1.45、63.91±1.53、63.68±1.80、63.57±1.65.The 5mg/kg resveratrol-treated group had no significant effect.(2) Behavior evaluation results from the relative long-term treatment study showed that resveratrol treatment remarkably improved the limb movement of rats with cerebral ischemia-reperfusion injury with statistical significance.i the weight variation ratio:The weight of rats in the sham-operated group were significantly increased,except On dl, The weight of rats in the model group were significantly decreased.compared with sham-operated group in same time, On 2th、4th、6th and 8th day the weight variation ratio after focal cerebral ischemia and reperfusion injury in the model group were significantly increased (-7.61±5.71,-10.57±10.49,12.40±12.29,12.05±13.52), compared with the model group,On 2th、4th and 6th day of the weight test, the resveratrol middle dose (10mg/kg) group were significantly decreased(-9.07±3.85,-9.44±11.97,-10.90±15.82,), On 4th and 6th day of the weight test, the resveratrol high dose (20mg/kg) group were significantly decreased(-12.15±12.80,-13.25±13.89,),the Positive control group were significantly decreased (-9.58±3.09,-9.12±6.56,-9.43±7.67,-7.50±8.46). ii Postural reflex test:On the Postural reflex test neurological score,compared with sham-operated group(0±0), On 2th、4th、6th and 8th day the model group were significantly increased(1.42±0.48,1.36±0.33, 1.29±0.51,0.91±0.30). compared with the model group,the resveratrol high dose (20mg/kg) group were significantly decreased(1.01±0.37,0.78±0.42,0.77±0.28, 0.59±0.39,). On 4th day the resveratrol low dose (5mg/kg) and middle dose(10mg/kg) group were significantly decreased(1.06±0.29,1.01±0.30),the Positive control group were significantly decreased (1.08±0.31,0.78±0.31,0.87±0.63,0.64±0.44).iii limb use asymmetry test:On limb use asymmetry test score, compared with sham-operated group(9.5±21.51,-0.75±25.77,4.25±23.64,4±24.42),On 2th、4th、6th and 8th day the model group were significantly increased (66.43±32.78,69.29±23.69, 50.36±17.81,51.79±40.03),compared with the model group, On 2th、4th and 6th day the resveratrol high dose (20mg/kg) group were significantly decreased(35.67±34.69, 29±27.33,28.33±27.82), On 4th day the resveratrol low dose (5mg/kg) and middle dose (10mg/kg) group were significantly decreased(47.5±18.60,46.88±19.07), On 2th、4th and 6th day the Positive control group were significantly decreased (26.56±29.98,44.38±28.57,33.13±27.5). (3) In the cell test, the cellular morphology of PC12 cells were altered after OGD. resveratrol (12.5μM,25μM,50μM) could significantly decrease the injury of PC 12 by OGD. compared with the model group (70.45±2.94), the MTT value of resveratrol group increased obviously:74.2±3.88, 92.55±5.08,90.3±4.55. In PC12 cells, compared with the model group (705.85±30.65), LDH leakage of resveratrol group decreased obviously: 630.76±31.28,619.72±23.91,599.34±37.54. In PC12 cells, compared with the model group (11.09±1.1), MDA leakage of resveratrol group decreased obviously: 9.43±0.53、9.27±0.84、7.82±0.63. In PC12 cells, compared with the model group (16.69±0.3), SOD leakage of resveratrol group increased obviously:17.67±0.23、18.79±0.26、18.68±0.15. In PC12 cells, compared with the model group (42.25±0.92), NO leakage of resveratrol group decreased obviously:31.25±2.11、25.88±2.06、25.38±2.73.
Conclusion:Resveratrol has protective effects on focal cerebral ischemia-reperfusion injury,which was demonstrated by significantly reducing the infarct size and brain edema and improves physical disabilities caused by ischemia. And resveratrol could exert a protective action on oxygen-glucose deprivation in PC12 cells.
方法：(1)采用栓线法制备大鼠急性局部脑缺血再灌注损伤模型(MCAO)。在剂量研究中,将大鼠随机分成7组：模型组、假手术组、阳性对照组、白藜芦醇苷各剂量组(5mg/kg、10mg/kg、20mg/kg、40mg/kg)。观察白藜芦醇苷对大鼠缺血大脑的梗塞面积及含水量的影响。(2)较长周期给药实验中,将大鼠随机分成6组：模型组、假手术组、阳性对照组、白藜芦醇苷高、中、低各剂量组,造模成功后第2、第4、第6、第8天,称量体重,分别采用姿势反射试验、肢体不对称试验两种方法作为行为学评价指标,观察白藜芦醇苷对大鼠缺血大脑的保护作用。(3)体外培养PC12细胞,应用化学方法建立细胞OGD损伤模型,观察细胞形态学改变,并且应用四甲基偶氮唑蓝法(methyl thiazolyl tetrazolium, MTT)观察不同浓度白藜芦醇苷对细胞活力的影响,测定细胞外液乳酸脱氢酶(Lactate dehydrogenase, LDH)浓度,一氧化氮(NO)及丙二醛(MDA)含量,超氧化物歧化酶(SOD)活性。
结果：(1)与大鼠模型组(28.30±7.92)比较,应用白藜芦醇苷后大鼠脑梗塞面积逐渐降低呈浓度依赖趋势分别为19.21±14.72、15.32±13.53、14.47±10.85、13.74±12.89。与大鼠模型组(65.81±1.75)比较,应用白藜芦醇苷后大鼠水肿程度逐渐降低呈浓度依赖趋势分别为64.27±1.45、63.91±1.53、63.68±1.80、63.57±1.65。白藜芦醇苷5mg/kg组有改善效果但无统计学意义。(2)较长周期给药后体重变化率及行为学评价结果显示：i体重变化率：假手术组除术后第1天体重下降,其余每天体重呈增长趋势。模型组由于缺血再灌注引起的损伤,造成体重呈下降趋势。(各时间点与给药前比较)体重变化率,与假手术组同时间点(1.26±8.40、4.44±6.84、7.22±6.18、10.80±5.81)比较,模型组造模后第2天、4天、6天和8天有显著性增加(-7.61±5.71、-10.57±10.49、-12.40±12.29、-12.05±13.52),有显著性差异(P＜0.01)。白藜芦醇苷低、中、高剂量组(5、10、20mg/kg)给药后可改善缺血再灌注引起的体重下降。同时间点体重变化率与模型组比较,中剂量组造模后第2天、4天和6天有显著性降低(-9.07±3.85、-9.44±11.97、-10.90±15.82),有显著性差异(P＜0.05)；高剂量组造模后第4天和6天有显著性降低(-12.15±12.80、-13.25±13.89),有显著性差异(P＜0.05)；阳性对照组给药可改善缺血再灌注引起的体重下降(-9.58±3.09、-9.12±6.56、-9.43±7.67、-7.50±8.46),且有显著性差异(P＜0.05)。ii姿势反射试验：造模后第2天、4天、6天和8天各时间点与假手术组(0±0)比较,模型组有显著性增加(1.42±0.48、1.36±0.33、1.29±0.51、0.91±0.30),具有显著性差异(P＜0.01)。白藜芦醇苷低、中、高剂量组(5、10、20mg/kg)给药后可改善缺血再灌注引起的肢体功能异常。与模型组比较,高剂量组能显著性降低缺血再灌注引起的肢体功能异常(1.01±0.37、0.78±0.42、0.77±0.28、0.59±0.39),具有显著性差异(P＜0.01)。与模型组比较,低、中剂量组在造模后第4天能显著性降低缺血再灌注引起的肢体功能异常(1.06±0.29、1.01±0.30),有显著性差异(P＜0.05)；阳性对照组给药可显著性降低缺血再灌注引起的肢体功能异常(1.08±0.31、0.78±0.31、0.87±0.63、0.64±0.44),且有显著性差异(P＜0.05)。iii肢体不对称试验：与假手术组(9.5±21.51、-0.75±25.77、4.25±23.64、4±24.42)比较,造模后第2天、4天、6天和8天各时间点模型组前肢不对称应用评分均显著升高(66.43±32.78、69.29±23.69、50.36±17.81、51.79±40.03),具有显著性差异(P＜0.05)。白藜芦醇苷低、中、高剂量组(5、10、20mg/kg)给药后可改善缺血再灌注引起的左前肢触及桶壁频率较少,右前肢触及桶壁频率较多。与模型组比较,高剂量组在造模后第2天、4天和6天能显著下降前肢不对称应用评分(35.67±34.69、29±27.33、28.33±27.82),具有显著性差异(P＜0.05)。与模型组比较,低、中剂量组在造模后第4天能显著下降前肢不对称应用评分(47.5±18.60、46.88±19.07),具有显著性差异(P＜0.05)；阳性对照组在造模后第2天、4天和6天能显著下降前肢不对称应用评分(26.56±29.98、44.38±28.57、33.13±27.5),且有显著性差异(P<0.05)。白藜芦醇苷能显著改善缺血引起的大鼠肢体活动障碍。(3)氧糖剥夺损伤后,PC12细胞形态发生了一定的改变,白藜芦醇苷12.5μM, 25μM,50μM三个剂量组显著降低了氧糖剥夺对PC12细胞成的损伤：PC12细胞的A值由模型的70.45±2.94增加到74.2±3.88、92.55±5.08、90.3±4.55；且有显著性差异(P<0.05)。与模型组705.85±30.65相比,应用白藜芦醇苷后PC12细胞各组细胞外液LDH活力(U/L)也逐渐降低呈浓度依赖趋势LDH分别为630.76±31.28、619.72±23.91、599.34±37.54,且有显著性差异(P＜0.05)。与模型组11.09±1.1相比,应用白藜芦醇苷后PC12细胞各组细胞外液MDA含量(nmol/mg)也逐渐降低呈浓度依赖趋势MDA分别为9.43±0.53、9.27±0.84、7.82±0.63，且有显著性差异(P＜0.05)。与模型组16.69±0.3相比,应用白藜芦醇苷后PC12细胞各组细胞外液SOD活性(U/mg)也逐渐增高呈浓度依赖趋势SOD分别17.67±0.23、18.79±0.26、18.68±0.15,且有显著性差异(P＜0.05)。与模型组42.25±0.92相比,应用白藜芦醇苷后PC12细胞各组细胞外液NO含量(μmol/g)也逐渐降低呈浓度依赖趋势NO分别为31.25±2.11、25.88±2.06、25.38±2.73,且有显著性差异(P＜0.05)。
结论：白藜芦醇苷对大鼠缺血大脑有保护作用,能明显减少大脑的梗塞面积和水肿程度,改善缺血引起的肢体行为障碍；离体细胞实验表明白藜芦醇苷对PC12细胞氧糖剥夺损伤具有保护作用。
Objective:To study the effect of resveratrol on the cerebral infarction and behavior in rats after focal cerebral ischemia-reperfusion injury. Based on this model, we also explore the possible mechanisms of the effect. Moreover, to investigate the effect of resveratrol on the viability and morphology of cell by establishing the oxygen-glucose deprivation (OGD) model in PC 12 cells.
Methods:(1)Rat model of focal cerebral ischemia reperfusion injury made by occlusion of middle cerebral artery was used. In the dose-dependence study, rats were randomly divided into 7 groups:model group, sham-operated group, positive control group, and resveratrol-treated groups (5mg/kg, 10mg/kg,20mg/kg and 40mg/kg). The size of cerebral infarction, the extent of edema and the water content were measured in the rats. (2)In the long-term experiment, the rats were randomly divided into 6 groups:model group, sham-operated group, positive control group, and resveratrol-treated groups of high, medium and low doses. Postural reflex test and limb use asymmetry test were performed as behavioral indexes on 2th,4th,6th and 8th day after the rats were subjected to focal cerebral ischemia-reperfusion injury for evaluating the protective effect of resveratrol on the brain damage. (3) By establishing oxygen-glucose deprivation (OGD) model of PC 12 cells in vitro, we observed the change of the cells. At the same time, MTT assay was applied to evaluate the cell's viability and biochemical method was used to determine LDH activity.the contents of nitric oxide(NO) and the malondialdehyde(MDA). the activity of superoxide dismutase(SOD).
Results:(1) Compared with model group(28.30±7.92), cerebral infarction area decreased obviously:19.21±14.72,15.32±13.53,14.47±10.85,13.74±12.89. Compared with model group(65.81±1.75),the extent of brain edema decreased obviously:64.27±1.45、63.91±1.53、63.68±1.80、63.57±1.65.The 5mg/kg resveratrol-treated group had no significant effect.(2) Behavior evaluation results from the relative long-term treatment study showed that resveratrol treatment remarkably improved the limb movement of rats with cerebral ischemia-reperfusion injury with statistical significance.i the weight variation ratio:The weight of rats in the sham-operated group were significantly increased,except On dl, The weight of rats in the model group were significantly decreased.compared with sham-operated group in same time, On 2th、4th、6th and 8th day the weight variation ratio after focal cerebral ischemia and reperfusion injury in the model group were significantly increased (-7.61±5.71,-10.57±10.49,12.40±12.29,12.05±13.52), compared with the model group,On 2th、4th and 6th day of the weight test, the resveratrol middle dose (10mg/kg) group were significantly decreased(-9.07±3.85,-9.44±11.97,-10.90±15.82,), On 4th and 6th day of the weight test, the resveratrol high dose (20mg/kg) group were significantly decreased(-12.15±12.80,-13.25±13.89,),the Positive control group were significantly decreased (-9.58±3.09,-9.12±6.56,-9.43±7.67,-7.50±8.46). ii Postural reflex test:On the Postural reflex test neurological score,compared with sham-operated group(0±0), On 2th、4th、6th and 8th day the model group were significantly increased(1.42±0.48,1.36±0.33, 1.29±0.51,0.91±0.30). compared with the model group,the resveratrol high dose (20mg/kg) group were significantly decreased(1.01±0.37,0.78±0.42,0.77±0.28, 0.59±0.39,). On 4th day the resveratrol low dose (5mg/kg) and middle dose(10mg/kg) group were significantly decreased(1.06±0.29,1.01±0.30),the Positive control group were significantly decreased (1.08±0.31,0.78±0.31,0.87±0.63,0.64±0.44).iii limb use asymmetry test:On limb use asymmetry test score, compared with sham-operated group(9.5±21.51,-0.75±25.77,4.25±23.64,4±24.42),On 2th、4th、6th and 8th day the model group were significantly increased (66.43±32.78,69.29±23.69, 50.36±17.81,51.79±40.03),compared with the model group, On 2th、4th and 6th day the resveratrol high dose (20mg/kg) group were significantly decreased(35.67±34.69, 29±27.33,28.33±27.82), On 4th day the resveratrol low dose (5mg/kg) and middle dose (10mg/kg) group were significantly decreased(47.5±18.60,46.88±19.07), On 2th、4th and 6th day the Positive control group were significantly decreased (26.56±29.98,44.38±28.57,33.13±27.5). (3) In the cell test, the cellular morphology of PC12 cells were altered after OGD. resveratrol (12.5μM,25μM,50μM) could significantly decrease the injury of PC 12 by OGD. compared with the model group (70.45±2.94), the MTT value of resveratrol group increased obviously:74.2±3.88, 92.55±5.08,90.3±4.55. In PC12 cells, compared with the model group (705.85±30.65), LDH leakage of resveratrol group decreased obviously: 630.76±31.28,619.72±23.91,599.34±37.54. In PC12 cells, compared with the model group (11.09±1.1), MDA leakage of resveratrol group decreased obviously: 9.43±0.53、9.27±0.84、7.82±0.63. In PC12 cells, compared with the model group (16.69±0.3), SOD leakage of resveratrol group increased obviously:17.67±0.23、18.79±0.26、18.68±0.15. In PC12 cells, compared with the model group (42.25±0.92), NO leakage of resveratrol group decreased obviously:31.25±2.11、25.88±2.06、25.38±2.73.
Conclusion:Resveratrol has protective effects on focal cerebral ischemia-reperfusion injury,which was demonstrated by significantly reducing the infarct size and brain edema and improves physical disabilities caused by ischemia. And resveratrol could exert a protective action on oxygen-glucose deprivation in PC12 cells.
引文
[1]冯树涛,尼莫地平注射液治疗脑梗死的疗效观察.临床医学,2006(06).
[2]单利华,朱志鑫,吴晨娟,丁雪萍,汤良春,还原性谷胱甘肽治疗急性脑梗死的疗效观察.心脑血管病防治,2006(03).
[3]郑华,杨波,周品山,李世芳,γ-氨酪酸治疗新生大鼠缺氧缺血性脑损伤的实验研究.中国新生儿科杂志,2006(05).
[4]樊丽超,于永发,张莹,cas pase抑制剂对大鼠缺血再灌注脑组织细胞凋亡和Aβ的影响.中国神经免疫学和神经病学杂志,2005(06).
[5]Ji, X., K. Li, W. Li, S. Li, F. Yan, W. Gong, and Y. Luo, The effects of blood pressure and urokinase on brain injuries after experimental cerebral infarction in rats. Neurol Res,2009.31(2):p.204-8.
[6]Hunter, A.J., J. Hatcher, D. Virley, P. Nelson, E. Irving, S.J. Hadingham, and A.A. Parsons, Functional assessments in mice and rats after focal stroke. Neuropharmacology,2000.39(5):p.806-16.
[7]Khaja, A.M. and J.C. Grotta, Established treatments for acute ischaemic stroke. Lancet,2007.369(9558):p.319-30.
[8]Hacke, W., G. Donnan, C. Fieschi, M. Kaste, R. von Kummer, J.P. Broderick, T. Brott, M. Frankel, J.C. Grotta, E.C. Haley, Jr., T. Kwiatkowski, S.R. Levine, C. Lewandowski, M. Lu, P. Lyden, J.R. Marler, S. Patel, B.C. Tilley, G. Albers, E. Bluhmki, M. Wilhelm, and S. Hamilton, Association of outcome with early stroke treatment:pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet,2004.363(9411):p.768-74.
[9]Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med,1995.333(24):p.1581-7.
[10]The International Stroke Trial (IST):a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. International Stroke Trial Collaborative Group. Lancet, 1997.349(9065):p.1569-81.
[11]Fink, J.N., M.H. Selim, S. Kumar, and G. Schlaug, Why are stroke patients excluded from tPA therapy? An analysis of patient eligibility. Neurology, 2001.57(9):p.1739-40.
[12]Heuschmann, P.U., K. Berger, B. Misselwitz, P. Hermanek, C. Leffinann, M. Adelmann, H.J. Buecker-Nott, J. Rother, B. Neundoerfer, and P.L. Kolominsky-Rabas, Frequency of thrombolytic therapy in patients with acute ischemic stroke and the risk of in-hospital mortality:the German Stroke Registers Study Group. Stroke,2003.34(5):p.1106-13.
[13]叶瑞东,韩军良,赵钢,缺血性脑卒中急性期神经保护治疗的研究进展.第四军医大学学报,2008(20).
[14]Wenzel, E. and V. Somoza, Metabolism and bioavailability of trans-resveratrol. Mol Nutr Food Res,2005.49(5):p.472-81.
[15]郭胜蓝,孙.欧.杨.徐.,虎杖苷对大鼠急性脑缺血再灌注损伤的保护作用.时珍国医国药,2005(05).
[16]Baur, J.A. and D.A. Sinclair, Therapeutic potential of resveratrol:the in vivo evidence. Nat Rev Drug Discov,2006.5(6):p.493-506.
[17]金春华,刘.赵.,虎杖甙对白细胞-内皮细胞粘附作用的影响.中国微循环,1999(02).
[18]金伟军,陈.钱.石.,虎杖晶4号对人血PMNs呼吸暴发和氧自由基的作用.中国药理学通报,1993(05).
[19]梁荣能,莫.,白黎芦醇甙对脑缺血损伤的抗自由基作用.中国药理学通报,1996(02).
[20]王佾先,亢.张.徐.,白藜芦醇苷的抗癌作用及对癌细胞周期的影响.浙江中西医结合杂志,2003(05).
[21]Zhu, X.L., L.Z. Xiong, Q. Wang, Z.G. Liu, X. Ma, Z.H. Zhu, S. Hu, G. Gong, and S.Y. Chen, Therapeutic time window and mechanism of tetramethylpyrazine on transient focal cerebral ischemia/reperfusion injury in rats. Neurosci Lett,2009.449(1):p.24-7.
[22]Jia, J., X. Zhang, Y.S. Hu, Y. Wu, Q.Z. Wang, N.N. Li, C.Q. Wu, H.X. Yu, and Q.C. Guo, Protective effect of tetraethyl pyrazine against focal cerebral ischemia/reperfusion injury in rats:therapeutic time window and its mechanism. Thromb Res,2009.123(5):p.727-30.
[23]Abe, T., A. Kunz, M. Shimamura, P. Zhou, J. Anrather, and C. Iadecola, The neuroprotective effect of prostaglandin E2 EP1 receptor inhibition has a wide therapeutic window, is sustained in time and is not sexually dimorphic. J Cereb Blood Flow Metab,2009.29(1):p.66-72.
[24]Ley, J.J., L. Belayev, I. Saul, D.A. Becker, and M.D. Ginsberg, Neuroprotective effect of STAZN, a novel azulenyl nitrone antioxidant, in focal cerebral ischemia in rats:dose-response and therapeutic window. Brain Res,2007.1180:p.101-10.
[25]Hua, Y., T. Schallert, R.F. Keep, J. Wu, J.T. Hoff, and G. Xi, Behavioral tests after intracerebral hemorrhage in the rat. Stroke,2002.33(10):p.2478-84.
[26]Zhang, L., T. Schallert, Z.G. Zhang, Q. Jiang, P. Arniego, Q. Li, M. Lu, and M. Chopp, A test for detecting long-term sensorimotor dysfunction in the mouse after focal cerebral ischemia. J Neurosci Methods,2002.117(2):p. 207-14.
[27]Peruche, B. and J. Krieglstein, Neuroblastoma cells for testing neuroprotective drug effects. J Pharmacol Methods,1991.26(2):p.139-48.
[28]Gomez, L.A., A.E. Alekseev, L.A. Aleksandrova, P.A. Brady, and A. Terzic, Use of the MTT assay in adult ventricular cardiomyocytes to assess viability: effects of adenosine and potassium on cellular survival. J Mol Cell Cardiol, 1997.29(4):p.1255-66.
[29]Markgraf, C.G., S. Kraydieh, R. Prado, B.D. Watson, W.D. Dietrich, and M.D. Ginsberg, Comparative histopathologic consequences of photothrombotic occlusion of the distal middle cerebral artery in Sprague-Dawley and Wistar rats. Stroke,1993.24(2):p.286-92; discussion 292-3.
[30]Fan, T., S.H. Yang, E. Johnson, B. Osteen, R. Hayes, A.L. Day, and J.W. Simpkins,17beta-Estradiol extends ischemic thresholds and exerts neuroprotective effects in cerebral subcortex against transient focal cerebral ischemia in rats. Brain Res,2003.993(1-2):p.10-7.
[31]Mehta, S.H., K.M. Dhandapani, L.M. De Sevilla, R.C. Webb, V.B. Mahesh, and D.W. Brann, Tamoxifen, a selective estrogen receptor modulator, reduces ischemic damage caused by middle cerebral artery occlusion in the ovariectomized female rat. Neuroendocrinology,2003.77(1):p.44-50.
[32]Lee, S.J., C.R. Campomanes, P.T. Sikat, A.T. Greenfield, P.B. Allen, and B.S. McEwen, Estrogen induces phosphorylation of cyclic AMP response element binding (pCREB) in primary hippocampal cells in a time-dependent manner. Neuroscience,2004.124(3):p.549-60.
[33]Prieto, R., F. Carceller, J.M. Roda, and C. Avendano, The intraluminal thread model revisited:rat strain differences in local cerebral blood flow. Neurol Res, 2005.27(1):p.47-52.
[34]王引明,刘春风,曹勇军,陈孝东,周媛,线栓法制作大鼠局灶性脑缺血／再灌注模型若干问题的探讨.苏州大学学报(医学版),2006(03).
[35]辛世萌,刘.聂.,栓线长度、直径及大鼠体重与栓线法大鼠局灶性脑缺血模型关系的研究.大连医科大学学报,2000(02).
[36]张平,朱斌,and李彤,线栓法制作大鼠局灶性脑缺血再灌注模型的改进与探讨.医学信息(手术学分册),2008(03).
[37]Shafer, T.J. and W.D. Atchison, Transmitter, ion channel and receptor properties of pheochromocytoma (PC 12) cells:a model for neurotoxicological studies. Neurotoxicology,1991.12(3):p.473-92.
[38]Tijburg, L.B., T. Mattern, J.D. Folts, U.M. Weisgerber, and M.B. Katan, Tea flavonoids and cardiovascular disease:a review. Crit Rev Food Sci Nutr,1997. 37(8):p.771-85.
[39]Ii, T., Y. Satomi, D. Katoh, J. Shimada, M. Baba, T. Okuyama, H. Nishino, and N. Kitamura, Induction of cell cycle arrest and p21(CIP1/WAF1) expression in human lung cancer cells by isoliquiritigenin. Cancer Lett,2004. 207(1):p.27-35.
[40]Namba, C., N. Adachi, K. Liu, T. Yorozuya, and T. Arai, Suppression of sodium pump activity and an increase in the intracellular Ca2+concentration by dexamethasone in acidotic mouse brain. Brain Res,2002.957(2):p.271-7.
[41]Puzzo, D.,0. Vitolo, F. Trinchese, J.P. Jacob, A. Palmeri, and 0. Arancio, Amyloid-beta peptide inhibits activation of the nitric oxide/cGMP/cAMP-responsive element-binding protein pathway during hippocampal synaptic plasticity. J Neurosci,2005.25(29):p.6887-97.
[42]Nottebohm, F., Neuronal replacement in adult brain. Brain Res Bull,2002. 57(6):p.737-49.
[43]Rice, A.C., A. Khaldi, H.B. Harvey, N.J. Salman, F. White, H. Fillmore, and M.R. Bullock, Proliferation and neuronal differentiation of mitotically active cells following traumatic brain injury. Exp Neurol,2003.183(2):p.406-17.
[44]Tanaka, R., K. Yamashiro, H. Mochizuki, N. Cho, M. Onodera, Y. Mizuno, and T. Urabe, Neurogenesis after transient global ischemia in the adult hippocampus visualized by improved retroviral vector. Stroke,2004.35(6):p. 1454-9.
[45]Zhu, L.L., T. Zhao, H.S. Li, H. Zhao, L.Y. Wu, A.S. Ding, W.H. Fan, and M. Fan, Neurogenesis in the adult rat brain after intermittent hypoxia. Brain Res, 2005.1055(1-2):p.1-6.
[46]Choi, Y.S., M.Y. Lee, K.W. Sung, S.W. Jeong, J.S. Choi, H.J. Park, O.N. Kim, S.B. Lee, and S.Y. Kim, Regional differences in enhanced neurogenesis in the dentate gyrus of adult rats after transient forebrain ischemia. Mol Cells,2003. 16(2):p.232-8.
[47]Yagita, Y., K. Kitagawa, T. Ohtsuki, K. Takasawa, T. Miyata, H. Okano, M. Hori, and M. Matsumoto, Neurogenesis by progenitor cells in the ischemic adult rat hippocampus. Stroke,2001.32(8):p.1890-6.
[48]Wei, J. and M.J. Quast, Effect of nitric oxide synthase inhibitor on a hyperglycemic rat model of reversible focal ischemia:detection of excitatory amino acids release and hydroxyl radical formation. Brain Res,1998. 791(1-2):p.146-56.
[49]梅和珊,王.,脑缺血时谷氨酸释放机制.中国药理学通报,2005(04).
[50]胡波,孙.梅.童.,银杏叶提取物对培养的海马神经元内谷氨酸诱导钙信号的影响.中国临床康复,2002(01).
[51]Lewen, A., P. Matz, and P.H. Chan, Free radical pathways in CNS injury. J Neurotrauma,2000.17(10):p.871-90.
[52]张敬伟, No,Sod与缺血性脑血管病的关系.中国误诊学杂志,2005(05).
[53]Iadecola, C, Bright and dark sides of nitric oxide in ischemic brain injury. Trends Neurosci,1997.20(3):p.132-9.
[54]Brune, B., A. von Knethen, and K.B. Sandau, Transcription factors p53 and HIF-lalpha as targets of nitric oxide. Cell Signal,2001.13(8):p.525-33.
[55]Hara, H., C. Ayata, P.L. Huang, C. Waeber, G. Ayata, M. Fujii, and M.A. Moskowitz, [3H]L-NG-nitroarginine binding after transient focal ischemia and NMDA-induced excitotoxicity in type I and type III nitric oxide synthase null mice. J Cereb Blood Flow Metab,1997.17(5):p.515-26.
[56]刘辉,一氧化氮、一氧化氮合酶与脑缺血损伤.国外医学.生理.病理科学与临床分册,1999(02).
[57]杨彦玲,肖.,一氧化氮合酶在缺血性脑损伤中的作用.陕西医学杂志,2003(12).
[58]王丹,朱.梁.王,阿司匹林对急性脑梗死患者血浆一氧化氮及血小板α颗粒膜蛋白的影响.中国实用内科杂志,2004(12).
[59]帅杰,董.,不同脑缺血和再灌流过程中大鼠脑组织no含量的动态变化.临床神经病学杂志,1997(06).
[60]Malinski, T., F. Bailey, Z.G. Zhang, and M. Chopp, Nitric oxide measured by a porphyrinic microsensor in rat brain after transient middle cerebral artery occlusion. J Cereb Blood Flow Metab,1993.13(3):p.355-8.
[61]Nishikawa, T., J.R. Kirsch, R.C. Koehler, D.S. Bredt, S.H. Snyder, and R.J. Traystman, Effect of nitric oxide synthase inhibition on cerebral blood flow and injury volume during focal ischemia in cats. Stroke,1993.24(11):p. 1717-24.
[62]方玲,王.吴.林.慕.,一氧化氮合酶在脑缺血再灌注中的双重作用.中国神经免疫学和神经病学杂志,2004(01).
[63]Goldberg, W.J., R.M. Kadingo, and J.N. Barrett, Effects of ischemia-like conditions on cultured neurons:protection by low Na+, low Ca2+solutions. J Neurosci,1986.6(11):p.3144-51.
[64]Coyle, J.T. and P. Puttfarcken, Oxidative stress, glutamate, and neurodegenerative disorders. Science,1993.262(5134):p.689-95.
[65]Gil, P., F. Farinas, A. Casado, and E. Lopez-Fernandez, Malondialdehyde:a possible marker of ageing. Gerontology,2002.48(4):p.209-14.
[66]Muradian,K.K., N.A. Utko, V. Fraifeld, T.G. Mozzhukhina, I.N. Pishel, and A.Y. Litoshenko, Superoxide dismutase, catalase and glutathione peroxidase activities in the liver of young and old mice:linear regression and correlation. Arch Gerontol Geriatr,2002.35(3):p.205-14.
[67]Ahuja-Jensen, P., S. Johnsen-Soriano, S. Ahuja, F. Bosch-Morell, M. Sancho-Tello, F.J. Romero, M. Abrahamson, and T. van Veen, Low glutathione peroxidase in rdl mouse retina increases oxidative stress and proteases. Neuroreport,2007.18(8):p.797-801.
[68]Zhou, Y., Y. Su, B. Li, F. Liu, J.W. Ryder, X. Wu, P.A. Gonzalez-DeWhitt, V. Gelfanova, J.E. Hale, P.C. May, S.M. Paul, and B. Ni, Nonsteroidal anti-inflammatory drugs can lower amyloidogenic Abeta42 by inhibiting Rho. Science,2003.302(5648):p.1215-7.
[1]Xu, Z., et al., Time window characteristics of cultured rat hippocampal neurons subjected to ischemia and reperfusion. Chin J Traumatol,2005.8(3): p.179-82.
[2]Pera, J., et al., Influence of chemical and ischemic preconditioning on cytokine expression after focal brain ischemia. J Neurosci Res,2004.78(1):p. 132-40.
[3]Green, D.R. and J.C. Reed, Mitochondria and apoptosis. Science,1998. 281(5381):p.1309-12.
[4]Frijns, C.J. and L.J. Kappelle, Inflammatory cell adhesion molecules in ischemic cerebrovascular disease. Stroke,2002.33(8):p.2115-22.
[5]Kontos, H.A., Oxygen radicals in cerebral ischemia:the 2001 Willis lecture. Stroke,2001.32(11):p.2712-6.
[6]陶祥洛!310009杭州,颅脑损伤.中华急诊医学杂志,2001(02).
[7]Bates, B., et al., Neurotrophin-3 promotes cell death induced in cerebral ischemia, oxygen-glucose deprivation, and oxidative stress:possible involvement of oxygen free radicals. Neurobiol Dis,2002.9(1):p.24-37.
[8]Nagy, Z., L. Simon, and Z. Bori, [Regulatory mechanisms in focal cerebral ischemia. New possibilities in neuroprotective therapy]. Ideggyogy Sz,2002. 55(3-4):p.73-85.
[9]Marks, A.R., Intracellular calcium-release channels:regulators of cell life and death. Am J Physiol,1997.272(2 Pt 2):p. H597-605.
[10]Etienne-Manneville, S., et al., ICAM-1-coupled cytoskeletal rearrangements and transendothelial lymphocyte migration involve intracellular calcium signaling in brain endothelial cell lines. J Immunol,2000.165(6):p.3375-83.
[11]Cummings, B.S., J. McHowat, and R.G Schnellmann, Role of an endoplasmic reticulum Ca2+-independent phospholipase A2 in cisplatin-induced renal cell apoptosis. J Pharmacol Exp Ther,2004.308(3):p.921-8.
[12]Lewen, A., P. Matz, and P.H. Chan, Free radical pathways in CNS injury. J Neurotrauma,2000.17(10):p.871-90.
[13]Tanaka, E., et al., Extrusion of intracellular calcium ion after in vitro ischemia in the rat hippocampal CA1 region. J Neurophysiol,2002.88(2):p.879-87.
[14]Niwa, M., et al., Time course of expression of three nitric oxide synthase isoforms after transient middle cerebral artery occlusion in rats. Neurol Med Chir (Tokyo),2001.41(2):p.63-72; discussion 72-3.
[15]Osuka, K., et al., Tamoxifen inhibits nitrotyrosine formation after reversible middle cerebral artery occlusion in the rat. J Neurochem,2001.76(6):p. 1842-50.
[16]Nakayama, R., et al., Effects of dantrolene on extracellular glutamate concentration and neuronal death in the rat hippocampal CA1 region subjected to transient ischemia. Anesthesiology,2002.96(3):p.705-10.
[17]Nishizawa, Y., Glutamate release and neuronal damage in ischemia. Life Sci, 2001.69(4):p.369-81.
[18]Ruehl, M.L., et al., Protective effects of inhibiting both blood and vascular selectins after stroke and reperfusion. Neurol Res,2002.24(3):p.226-32.
[19]Kokubo, Y., et al., Correlation between changes in apparent diffusion coefficient and induction of heat shock protein, cell-specific injury marker expression, and protein synthesis reduction on diffusion-weighted magnetic resonance images after temporary focal cerebral ischemia in rats. J Neurosurg, 2002.96(6):p.1084-93.
[20]Gu, Z., Q. Jiang, and G Zhang, Extracellular signal-regulated kinase and c-Jun N-terminal protein kinase in ischemic tolerance. Neuroreport,2001.12(16):p. 3487-91.
[21]Tenneti,L.,etal.,Roleofcaspases in N-methyl-D-aspartate-induced apoptosis in cerebrocortical neurons. J Neurochem,1998.71(3):p.946-59.
[2]单利华,朱志鑫,吴晨娟,丁雪萍,汤良春,还原性谷胱甘肽治疗急性脑梗死的疗效观察.心脑血管病防治,2006(03).
[3]郑华,杨波,周品山,李世芳,γ-氨酪酸治疗新生大鼠缺氧缺血性脑损伤的实验研究.中国新生儿科杂志,2006(05).
[4]樊丽超,于永发,张莹,cas pase抑制剂对大鼠缺血再灌注脑组织细胞凋亡和Aβ的影响.中国神经免疫学和神经病学杂志,2005(06).
[5]Ji, X., K. Li, W. Li, S. Li, F. Yan, W. Gong, and Y. Luo, The effects of blood pressure and urokinase on brain injuries after experimental cerebral infarction in rats. Neurol Res,2009.31(2):p.204-8.
[6]Hunter, A.J., J. Hatcher, D. Virley, P. Nelson, E. Irving, S.J. Hadingham, and A.A. Parsons, Functional assessments in mice and rats after focal stroke. Neuropharmacology,2000.39(5):p.806-16.
[7]Khaja, A.M. and J.C. Grotta, Established treatments for acute ischaemic stroke. Lancet,2007.369(9558):p.319-30.
[8]Hacke, W., G. Donnan, C. Fieschi, M. Kaste, R. von Kummer, J.P. Broderick, T. Brott, M. Frankel, J.C. Grotta, E.C. Haley, Jr., T. Kwiatkowski, S.R. Levine, C. Lewandowski, M. Lu, P. Lyden, J.R. Marler, S. Patel, B.C. Tilley, G. Albers, E. Bluhmki, M. Wilhelm, and S. Hamilton, Association of outcome with early stroke treatment:pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet,2004.363(9411):p.768-74.
[9]Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med,1995.333(24):p.1581-7.
[10]The International Stroke Trial (IST):a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. International Stroke Trial Collaborative Group. Lancet, 1997.349(9065):p.1569-81.
[11]Fink, J.N., M.H. Selim, S. Kumar, and G. Schlaug, Why are stroke patients excluded from tPA therapy? An analysis of patient eligibility. Neurology, 2001.57(9):p.1739-40.
[12]Heuschmann, P.U., K. Berger, B. Misselwitz, P. Hermanek, C. Leffinann, M. Adelmann, H.J. Buecker-Nott, J. Rother, B. Neundoerfer, and P.L. Kolominsky-Rabas, Frequency of thrombolytic therapy in patients with acute ischemic stroke and the risk of in-hospital mortality:the German Stroke Registers Study Group. Stroke,2003.34(5):p.1106-13.
[13]叶瑞东,韩军良,赵钢,缺血性脑卒中急性期神经保护治疗的研究进展.第四军医大学学报,2008(20).
[14]Wenzel, E. and V. Somoza, Metabolism and bioavailability of trans-resveratrol. Mol Nutr Food Res,2005.49(5):p.472-81.
[15]郭胜蓝,孙.欧.杨.徐.,虎杖苷对大鼠急性脑缺血再灌注损伤的保护作用.时珍国医国药,2005(05).
[16]Baur, J.A. and D.A. Sinclair, Therapeutic potential of resveratrol:the in vivo evidence. Nat Rev Drug Discov,2006.5(6):p.493-506.
[17]金春华,刘.赵.,虎杖甙对白细胞-内皮细胞粘附作用的影响.中国微循环,1999(02).
[18]金伟军,陈.钱.石.,虎杖晶4号对人血PMNs呼吸暴发和氧自由基的作用.中国药理学通报,1993(05).
[19]梁荣能,莫.,白黎芦醇甙对脑缺血损伤的抗自由基作用.中国药理学通报,1996(02).
[20]王佾先,亢.张.徐.,白藜芦醇苷的抗癌作用及对癌细胞周期的影响.浙江中西医结合杂志,2003(05).
[21]Zhu, X.L., L.Z. Xiong, Q. Wang, Z.G. Liu, X. Ma, Z.H. Zhu, S. Hu, G. Gong, and S.Y. Chen, Therapeutic time window and mechanism of tetramethylpyrazine on transient focal cerebral ischemia/reperfusion injury in rats. Neurosci Lett,2009.449(1):p.24-7.
[22]Jia, J., X. Zhang, Y.S. Hu, Y. Wu, Q.Z. Wang, N.N. Li, C.Q. Wu, H.X. Yu, and Q.C. Guo, Protective effect of tetraethyl pyrazine against focal cerebral ischemia/reperfusion injury in rats:therapeutic time window and its mechanism. Thromb Res,2009.123(5):p.727-30.
[23]Abe, T., A. Kunz, M. Shimamura, P. Zhou, J. Anrather, and C. Iadecola, The neuroprotective effect of prostaglandin E2 EP1 receptor inhibition has a wide therapeutic window, is sustained in time and is not sexually dimorphic. J Cereb Blood Flow Metab,2009.29(1):p.66-72.
[24]Ley, J.J., L. Belayev, I. Saul, D.A. Becker, and M.D. Ginsberg, Neuroprotective effect of STAZN, a novel azulenyl nitrone antioxidant, in focal cerebral ischemia in rats:dose-response and therapeutic window. Brain Res,2007.1180:p.101-10.
[25]Hua, Y., T. Schallert, R.F. Keep, J. Wu, J.T. Hoff, and G. Xi, Behavioral tests after intracerebral hemorrhage in the rat. Stroke,2002.33(10):p.2478-84.
[26]Zhang, L., T. Schallert, Z.G. Zhang, Q. Jiang, P. Arniego, Q. Li, M. Lu, and M. Chopp, A test for detecting long-term sensorimotor dysfunction in the mouse after focal cerebral ischemia. J Neurosci Methods,2002.117(2):p. 207-14.
[27]Peruche, B. and J. Krieglstein, Neuroblastoma cells for testing neuroprotective drug effects. J Pharmacol Methods,1991.26(2):p.139-48.
[28]Gomez, L.A., A.E. Alekseev, L.A. Aleksandrova, P.A. Brady, and A. Terzic, Use of the MTT assay in adult ventricular cardiomyocytes to assess viability: effects of adenosine and potassium on cellular survival. J Mol Cell Cardiol, 1997.29(4):p.1255-66.
[29]Markgraf, C.G., S. Kraydieh, R. Prado, B.D. Watson, W.D. Dietrich, and M.D. Ginsberg, Comparative histopathologic consequences of photothrombotic occlusion of the distal middle cerebral artery in Sprague-Dawley and Wistar rats. Stroke,1993.24(2):p.286-92; discussion 292-3.
[30]Fan, T., S.H. Yang, E. Johnson, B. Osteen, R. Hayes, A.L. Day, and J.W. Simpkins,17beta-Estradiol extends ischemic thresholds and exerts neuroprotective effects in cerebral subcortex against transient focal cerebral ischemia in rats. Brain Res,2003.993(1-2):p.10-7.
[31]Mehta, S.H., K.M. Dhandapani, L.M. De Sevilla, R.C. Webb, V.B. Mahesh, and D.W. Brann, Tamoxifen, a selective estrogen receptor modulator, reduces ischemic damage caused by middle cerebral artery occlusion in the ovariectomized female rat. Neuroendocrinology,2003.77(1):p.44-50.
[32]Lee, S.J., C.R. Campomanes, P.T. Sikat, A.T. Greenfield, P.B. Allen, and B.S. McEwen, Estrogen induces phosphorylation of cyclic AMP response element binding (pCREB) in primary hippocampal cells in a time-dependent manner. Neuroscience,2004.124(3):p.549-60.
[33]Prieto, R., F. Carceller, J.M. Roda, and C. Avendano, The intraluminal thread model revisited:rat strain differences in local cerebral blood flow. Neurol Res, 2005.27(1):p.47-52.
[34]王引明,刘春风,曹勇军,陈孝东,周媛,线栓法制作大鼠局灶性脑缺血／再灌注模型若干问题的探讨.苏州大学学报(医学版),2006(03).
[35]辛世萌,刘.聂.,栓线长度、直径及大鼠体重与栓线法大鼠局灶性脑缺血模型关系的研究.大连医科大学学报,2000(02).
[36]张平,朱斌,and李彤,线栓法制作大鼠局灶性脑缺血再灌注模型的改进与探讨.医学信息(手术学分册),2008(03).
[37]Shafer, T.J. and W.D. Atchison, Transmitter, ion channel and receptor properties of pheochromocytoma (PC 12) cells:a model for neurotoxicological studies. Neurotoxicology,1991.12(3):p.473-92.
[38]Tijburg, L.B., T. Mattern, J.D. Folts, U.M. Weisgerber, and M.B. Katan, Tea flavonoids and cardiovascular disease:a review. Crit Rev Food Sci Nutr,1997. 37(8):p.771-85.
[39]Ii, T., Y. Satomi, D. Katoh, J. Shimada, M. Baba, T. Okuyama, H. Nishino, and N. Kitamura, Induction of cell cycle arrest and p21(CIP1/WAF1) expression in human lung cancer cells by isoliquiritigenin. Cancer Lett,2004. 207(1):p.27-35.
[40]Namba, C., N. Adachi, K. Liu, T. Yorozuya, and T. Arai, Suppression of sodium pump activity and an increase in the intracellular Ca2+concentration by dexamethasone in acidotic mouse brain. Brain Res,2002.957(2):p.271-7.
[41]Puzzo, D.,0. Vitolo, F. Trinchese, J.P. Jacob, A. Palmeri, and 0. Arancio, Amyloid-beta peptide inhibits activation of the nitric oxide/cGMP/cAMP-responsive element-binding protein pathway during hippocampal synaptic plasticity. J Neurosci,2005.25(29):p.6887-97.
[42]Nottebohm, F., Neuronal replacement in adult brain. Brain Res Bull,2002. 57(6):p.737-49.
[43]Rice, A.C., A. Khaldi, H.B. Harvey, N.J. Salman, F. White, H. Fillmore, and M.R. Bullock, Proliferation and neuronal differentiation of mitotically active cells following traumatic brain injury. Exp Neurol,2003.183(2):p.406-17.
[44]Tanaka, R., K. Yamashiro, H. Mochizuki, N. Cho, M. Onodera, Y. Mizuno, and T. Urabe, Neurogenesis after transient global ischemia in the adult hippocampus visualized by improved retroviral vector. Stroke,2004.35(6):p. 1454-9.
[45]Zhu, L.L., T. Zhao, H.S. Li, H. Zhao, L.Y. Wu, A.S. Ding, W.H. Fan, and M. Fan, Neurogenesis in the adult rat brain after intermittent hypoxia. Brain Res, 2005.1055(1-2):p.1-6.
[46]Choi, Y.S., M.Y. Lee, K.W. Sung, S.W. Jeong, J.S. Choi, H.J. Park, O.N. Kim, S.B. Lee, and S.Y. Kim, Regional differences in enhanced neurogenesis in the dentate gyrus of adult rats after transient forebrain ischemia. Mol Cells,2003. 16(2):p.232-8.
[47]Yagita, Y., K. Kitagawa, T. Ohtsuki, K. Takasawa, T. Miyata, H. Okano, M. Hori, and M. Matsumoto, Neurogenesis by progenitor cells in the ischemic adult rat hippocampus. Stroke,2001.32(8):p.1890-6.
[48]Wei, J. and M.J. Quast, Effect of nitric oxide synthase inhibitor on a hyperglycemic rat model of reversible focal ischemia:detection of excitatory amino acids release and hydroxyl radical formation. Brain Res,1998. 791(1-2):p.146-56.
[49]梅和珊,王.,脑缺血时谷氨酸释放机制.中国药理学通报,2005(04).
[50]胡波,孙.梅.童.,银杏叶提取物对培养的海马神经元内谷氨酸诱导钙信号的影响.中国临床康复,2002(01).
[51]Lewen, A., P. Matz, and P.H. Chan, Free radical pathways in CNS injury. J Neurotrauma,2000.17(10):p.871-90.
[52]张敬伟, No,Sod与缺血性脑血管病的关系.中国误诊学杂志,2005(05).
[53]Iadecola, C, Bright and dark sides of nitric oxide in ischemic brain injury. Trends Neurosci,1997.20(3):p.132-9.
[54]Brune, B., A. von Knethen, and K.B. Sandau, Transcription factors p53 and HIF-lalpha as targets of nitric oxide. Cell Signal,2001.13(8):p.525-33.
[55]Hara, H., C. Ayata, P.L. Huang, C. Waeber, G. Ayata, M. Fujii, and M.A. Moskowitz, [3H]L-NG-nitroarginine binding after transient focal ischemia and NMDA-induced excitotoxicity in type I and type III nitric oxide synthase null mice. J Cereb Blood Flow Metab,1997.17(5):p.515-26.
[56]刘辉,一氧化氮、一氧化氮合酶与脑缺血损伤.国外医学.生理.病理科学与临床分册,1999(02).
[57]杨彦玲,肖.,一氧化氮合酶在缺血性脑损伤中的作用.陕西医学杂志,2003(12).
[58]王丹,朱.梁.王,阿司匹林对急性脑梗死患者血浆一氧化氮及血小板α颗粒膜蛋白的影响.中国实用内科杂志,2004(12).
[59]帅杰,董.,不同脑缺血和再灌流过程中大鼠脑组织no含量的动态变化.临床神经病学杂志,1997(06).
[60]Malinski, T., F. Bailey, Z.G. Zhang, and M. Chopp, Nitric oxide measured by a porphyrinic microsensor in rat brain after transient middle cerebral artery occlusion. J Cereb Blood Flow Metab,1993.13(3):p.355-8.
[61]Nishikawa, T., J.R. Kirsch, R.C. Koehler, D.S. Bredt, S.H. Snyder, and R.J. Traystman, Effect of nitric oxide synthase inhibition on cerebral blood flow and injury volume during focal ischemia in cats. Stroke,1993.24(11):p. 1717-24.
[62]方玲,王.吴.林.慕.,一氧化氮合酶在脑缺血再灌注中的双重作用.中国神经免疫学和神经病学杂志,2004(01).
[63]Goldberg, W.J., R.M. Kadingo, and J.N. Barrett, Effects of ischemia-like conditions on cultured neurons:protection by low Na+, low Ca2+solutions. J Neurosci,1986.6(11):p.3144-51.
[64]Coyle, J.T. and P. Puttfarcken, Oxidative stress, glutamate, and neurodegenerative disorders. Science,1993.262(5134):p.689-95.
[65]Gil, P., F. Farinas, A. Casado, and E. Lopez-Fernandez, Malondialdehyde:a possible marker of ageing. Gerontology,2002.48(4):p.209-14.
[66]Muradian,K.K., N.A. Utko, V. Fraifeld, T.G. Mozzhukhina, I.N. Pishel, and A.Y. Litoshenko, Superoxide dismutase, catalase and glutathione peroxidase activities in the liver of young and old mice:linear regression and correlation. Arch Gerontol Geriatr,2002.35(3):p.205-14.
[67]Ahuja-Jensen, P., S. Johnsen-Soriano, S. Ahuja, F. Bosch-Morell, M. Sancho-Tello, F.J. Romero, M. Abrahamson, and T. van Veen, Low glutathione peroxidase in rdl mouse retina increases oxidative stress and proteases. Neuroreport,2007.18(8):p.797-801.
[68]Zhou, Y., Y. Su, B. Li, F. Liu, J.W. Ryder, X. Wu, P.A. Gonzalez-DeWhitt, V. Gelfanova, J.E. Hale, P.C. May, S.M. Paul, and B. Ni, Nonsteroidal anti-inflammatory drugs can lower amyloidogenic Abeta42 by inhibiting Rho. Science,2003.302(5648):p.1215-7.
[1]Xu, Z., et al., Time window characteristics of cultured rat hippocampal neurons subjected to ischemia and reperfusion. Chin J Traumatol,2005.8(3): p.179-82.
[2]Pera, J., et al., Influence of chemical and ischemic preconditioning on cytokine expression after focal brain ischemia. J Neurosci Res,2004.78(1):p. 132-40.
[3]Green, D.R. and J.C. Reed, Mitochondria and apoptosis. Science,1998. 281(5381):p.1309-12.
[4]Frijns, C.J. and L.J. Kappelle, Inflammatory cell adhesion molecules in ischemic cerebrovascular disease. Stroke,2002.33(8):p.2115-22.
[5]Kontos, H.A., Oxygen radicals in cerebral ischemia:the 2001 Willis lecture. Stroke,2001.32(11):p.2712-6.
[6]陶祥洛!310009杭州,颅脑损伤.中华急诊医学杂志,2001(02).
[7]Bates, B., et al., Neurotrophin-3 promotes cell death induced in cerebral ischemia, oxygen-glucose deprivation, and oxidative stress:possible involvement of oxygen free radicals. Neurobiol Dis,2002.9(1):p.24-37.
[8]Nagy, Z., L. Simon, and Z. Bori, [Regulatory mechanisms in focal cerebral ischemia. New possibilities in neuroprotective therapy]. Ideggyogy Sz,2002. 55(3-4):p.73-85.
[9]Marks, A.R., Intracellular calcium-release channels:regulators of cell life and death. Am J Physiol,1997.272(2 Pt 2):p. H597-605.
[10]Etienne-Manneville, S., et al., ICAM-1-coupled cytoskeletal rearrangements and transendothelial lymphocyte migration involve intracellular calcium signaling in brain endothelial cell lines. J Immunol,2000.165(6):p.3375-83.
[11]Cummings, B.S., J. McHowat, and R.G Schnellmann, Role of an endoplasmic reticulum Ca2+-independent phospholipase A2 in cisplatin-induced renal cell apoptosis. J Pharmacol Exp Ther,2004.308(3):p.921-8.
[12]Lewen, A., P. Matz, and P.H. Chan, Free radical pathways in CNS injury. J Neurotrauma,2000.17(10):p.871-90.
[13]Tanaka, E., et al., Extrusion of intracellular calcium ion after in vitro ischemia in the rat hippocampal CA1 region. J Neurophysiol,2002.88(2):p.879-87.
[14]Niwa, M., et al., Time course of expression of three nitric oxide synthase isoforms after transient middle cerebral artery occlusion in rats. Neurol Med Chir (Tokyo),2001.41(2):p.63-72; discussion 72-3.
[15]Osuka, K., et al., Tamoxifen inhibits nitrotyrosine formation after reversible middle cerebral artery occlusion in the rat. J Neurochem,2001.76(6):p. 1842-50.
[16]Nakayama, R., et al., Effects of dantrolene on extracellular glutamate concentration and neuronal death in the rat hippocampal CA1 region subjected to transient ischemia. Anesthesiology,2002.96(3):p.705-10.
[17]Nishizawa, Y., Glutamate release and neuronal damage in ischemia. Life Sci, 2001.69(4):p.369-81.
[18]Ruehl, M.L., et al., Protective effects of inhibiting both blood and vascular selectins after stroke and reperfusion. Neurol Res,2002.24(3):p.226-32.
[19]Kokubo, Y., et al., Correlation between changes in apparent diffusion coefficient and induction of heat shock protein, cell-specific injury marker expression, and protein synthesis reduction on diffusion-weighted magnetic resonance images after temporary focal cerebral ischemia in rats. J Neurosurg, 2002.96(6):p.1084-93.
[20]Gu, Z., Q. Jiang, and G Zhang, Extracellular signal-regulated kinase and c-Jun N-terminal protein kinase in ischemic tolerance. Neuroreport,2001.12(16):p. 3487-91.
[21]Tenneti,L.,etal.,Roleofcaspases in N-methyl-D-aspartate-induced apoptosis in cerebrocortical neurons. J Neurochem,1998.71(3):p.946-59.