依达拉奉对脑缺血再灌注大鼠海马一氧化氮的影响

目的研究依达拉奉对脑缺血再灌注大鼠海马一氧化氮(NO)产生的影响。方法大鼠脑缺血采用四血管阻断法,选择性测定电极检测的浓度。实验分为生理盐水组、依达拉奉组(Edaravone)和7-Nitroindazole(7-NI)组。结果依达拉奉和7-NI皆未影响大鼠的血压和海马血流量,均显著减少了缺血再灌注时海马内NO的产生(均P<0.001)。结论依达拉奉可能通过抑制神经型一氧化氮合酶(nNOS)或减少NO而起到神经保护作用。     

脑缺血对局部超氧化物歧化酶,丙二醛水平的影响

建立大鼠右大脑中动脉栓塞（Ｒ－ＭＣＡＯ）模型,检测局部缺血后不同时间左右脑组织超氧化物歧化酶（ＳＯＤ）、丙二醛（ＭＤＡ）的含量,发现Ｒ－ＭＣＡＯ１０分钟始,缺血脑组织ＳＯＤ即降低,至３０分钟后恢复,而ＭＤＡ则在Ｒ－ＭＣＡＯ６０分钟后持续升高。说明缺血后ＳＯＤ活力下降、致ＭＤＡ蓄积,是造成脑组织损伤的机制之一。     

托吡酯对大鼠脑缺血再灌注后血清超氧化物歧化酶活性、丙二醛含量及神经功能的影响

目的探讨托吡酯(TPM)对大鼠脑缺血再灌注后血清超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量和神经功能的影响。方法将SD大鼠随机分为缺血再灌注组、TPM组及假手术组;采用线栓法建立大鼠大脑中动脉闭塞模型,TPM组动物分别于插线和再灌注时腹腔注射TPM混悬液(8mg/ml,80mg/kg);各组术后24h时进行神经功能评分后处死动物。采用羟胺氧化法测定血清SOD活性及硫代巴比妥酸法测定血清MDA含量。结果血清SOD活性及MDA含量缺血再灌注组分别为(157.72±19.04)U/ml及(7.45±0.84)nmol/ml,TPM组分别为(171.25±15.72)U/ml及(6.10±0.98)nmol/ml,假手术组分别为(179.74±7.95)U/ml及(5.90±0.72)nmol/ml;与TPM组及假手术组相比,缺血再灌注组大鼠血清SOD活性明显降低,MDA含量明显升高(均P<0.05)。TPM组及假手术组间血清SOD活性和MDA含量差异无显著性。TPM组神经功能评分较缺血再灌注组有显著改善(P<0.05)。结论TPM能减少脑缺血再灌注大鼠脑组织中抗氧化酶的消耗,有效抑制氧自由基的产生及其毒性,具有减轻脑缺血神经功能障碍的作用。     

依达拉奉对大鼠延髓缺血后超氧化物歧化酶、丙二醛的影响

目的 探讨依达拉奉对大鼠延髓缺血中的影响.方法 将Wistar大鼠分为假手术组、依达拉奉干预组(干预组)、延髓缺血模型组(模型组),采用多点阻断脑动脉方法制造延髓缺血模型.依达拉奉干预组腹腔注射依达拉奉;延髓缺血模型组腹腔注射生理盐水.分别在实验7d、14d时取延髓,检测脑组织的含水量、SOD、MDA水平.结果 延髓缺血模型组脑组织SOD水平下降,脑组织MDA浓度先升高后降低;与延髓缺血模型组相比,干预组SOD下降的幅度小(P＜0.01),MDA浓度降低;干预组脑组织含水量明显低于延髓缺血模型组(P＜0.01).结论 依达拉奉有效清除自由基,对延髓缺血具有明显保护作用.     

依达拉奉对脑出血大鼠脑组织丙二醛含量、超氧化物歧化酶活力及脑水含量的影响

目的研究依达拉奉对实验性脑出血大鼠氧自由基反应及脑水含量的影响。方法采用立体定向自体血注入法制作实验性脑出血大鼠模型,依达拉奉组在制作模型前后给予依达拉奉腹腔注射;脑出血组大鼠不予干预;脑组织氧自由基丙二醛(MDA)含量测定采用硫代巴比妥酸法,超氧化物歧化酶(SOD)活力测定采用黄嘌呤氧化法,脑水含量测定采用干湿重法。并与假手术大鼠(对照组)比较。结果脑出血组MDA含量较对照组显著增加(P<0.01)、SOD活力显著降低(P<0.01)、脑水含量增加(P<0.05～0.01)。依达拉奉治疗组与脑出血组比较,在脑出血后1d、3d、7dMDA含量均显著降低(P<0.05～0.01),SOD活力显著提高(P<0.05～0.01),脑水含量降低(均P<0.05)。结论依达拉奉能降低实验性脑出血大鼠脑组织MDA含量、提高SOD活力、减轻脑水肿,对实验性脑出血大鼠有脑保护效应。     

依达拉奉对慢性脑缺血大鼠一氧化氮及一氧化氮合酶阳性神经元数量的影响

目的观察依达拉奉对脑缺血大鼠脑组织NO含量及NOS阳性神经元数量的影响,为临床上防治慢性脑缺血引发的疾病提供指导。方法 54只Wistar大鼠,分为NO含量组和NOS阳性神经元组,每组再分为模型组、治疗组、假手术组,利用结扎大鼠两侧颈总动脉制作大鼠慢性脑缺血模型,硝酸还原酶法测NO含量,NADPH-d组织化学方法染色NOS阳性神经元,光镜下观察。结果治疗组各时间点NO含量和NOS阳性神经元数量较模型组减少。结论依达拉奉对慢性脑缺血大鼠脑组织具有保护作用。     

依达拉奉对脑缺血-再灌注大鼠的神经保护作用及其机制研究

目的探讨依达拉奉对局灶性脑缺血-再灌注损伤的影响及其可能的神经保护机制。方法用线栓法制备大鼠局灶性脑缺血-再灌注损伤模型,用试剂盒检测脑组织丙二醛(MDA)含量和一氧化氮合酶(NOS)活性;分别测定脑组织含水量;免疫组织化学染色检测水通道蛋白4(AQP-4)的表达水平。结果缺血再灌注损伤后,大鼠脑组织脂质过氧化产物丙二醛含量和一氧化氮合酶活性增高,MDA含量和NOS合酶活性于脑缺血-再灌注后30min开始增高,于3d达到高峰,于7d基本恢复正常;脑组织含水量于脑缺血再灌注后1d开始增高,于3d达到高峰,于7d时下降至大致正常水平;AQP-4的表达于脑缺血-再灌注后6h开始增高,于3d达到高峰,于7d时下降至大致正常水平。依达拉奉干预能显著降低MDA含量和NOS活性,降低脑组织的含水量,并使AQP-4的表达明显下降。结论在脑缺血-再灌注损伤后,依达拉奉能通过清除自由基而减轻脂质过氧化损伤,并通过抑制AQP-4的表达减轻脑水肿,从而起到神经保护作用。     

依达拉奉对帕金森病大鼠模型的神经保护作用及黑质纹状体丙二醛和一氧化氮水平的影响

目的 探讨依达拉奉对帕金森病(PD)大鼠的神经保护作用及黑质纹状体丙二醛(MDA)和一氧化氮(NO)水平的影响.方法 将72只SD大鼠随机分为正常对照组(n=12)、生理盐水对照组(NS组,n=12)、依达拉奉治疗组(ED组,n=48),ED组又分为ED 0.3 mg、1 mg、3 mg及3 mg停药后亚组,每个亚组12只大鼠.在大鼠脑内注入6-羟基多巴胺(6-OHDA)制作PD模型,术后各组大鼠分别相应给予NS 1 ml及ED 0.3 mg/kg、1 mg/kg、3 mg/kg腹腔注射,每天2次,连续14 d.对各组大鼠并进行旋转试验;用免疫组化染色检测黑质酪氨酸羟化酶(TH)阳性细胞数,化学比色法检测黑质纹状体MDA和NO水平.结果 正常对照组大鼠旋转圈数与NS组及ED各亚组比较,差异有统计学意义(均P＜0.01).ED 3 mg及ED 3 mg停药后亚组的旋转圈数显著少于NS组及ED 0.3 mg、1 mg亚组(均P＜0.05).NS组及各ED亚组左侧黑质TH阳性神经元显著少于正常对照组及右侧(均P ＜0.05).ED 3 mg及ED 3 mg停药后亚组左侧黑质TH阳性神经元显著多于NS组和ED 0.3 mg、1 mg亚组(均P＜0.05).与正常对照组比较,NS组和各ED亚组黑质、纹状体NO和MDA水平显著升高(均P＜0.01).ED 3 mg及ED 3 mg停药后亚组黑质、纹状体NO和MDA水平较NS组和ED 0.3 mg、1 mg亚组显著降低(均P＜0.05).结论 依达拉奉对PD大鼠的神经保护作用呈剂量依赖性;其能抑制过氧化反应,降低PD大鼠黑质纹状体的MDA、NO水平.     

依达拉奉预处理对小鼠脑缺血再灌注损伤后皮质一氧化氮合酶表达的影响

目的探讨依达拉奉预处理对小鼠脑缺血再灌注(IR)损伤后皮质一氧化氮合酶(NOS)表达的影响。方法 48只健康ICR小鼠被分为假手术组、对照组和依达拉奉组。依达拉奉组和对照组分别给予依达拉奉3 mg/(kg.d)和同等体积的生理盐水腹腔注射共7 d,然后建立小鼠IR模型;缺血1 h、再灌注24 h时应用2,3,5-氯化三苯基四氮唑(TTC)染色法测量各组脑梗死体积,应用免疫组化法检测各组小鼠皮质神经元型、、诱导型和内皮型NOS(nNOS、iNOS、eNOS)阳性细胞数。结果与假手术组比较,对照组小鼠皮质nNOS、iNOS和eNOS阳性细胞数明显增多(均P<0.05);与对照组比较,依达拉奉组脑梗死体积明显缩小,皮质nNOS和iNOS阳性细胞数明显减少,eNOS阳性细胞数明显增多(均P<0.05)。结论依达拉奉预处理可以影响IR小鼠皮质nNOS、iNOS和eNOS的表达,发挥神经保护作用。     

西比灵对鼠脑缺血再灌注损伤模型的血清及脑组织中SOD、MDA、N0、NOS含量及病理学的影响

目的 研究西比灵对鼠脑缺血再灌注损伤模型的血清及脑组织中超氧化物歧化酶(SOD)、丙二醛(MDA)、一氧化氮(NO)、一氧化氮合酶(NOS)的含量及病理学改变的影响。方法 选用21只沙土鼠并随机分为3组,脑缺血再灌注组(再灌注组)、西比灵预防组(预防组)及对照组,每组7只,分别测定血清、脑组织中SOD、MDA、NO、NOS的含量,并用电镜检测其病理学的变化。结果 与对照组比较,再灌注组显示严重的病理损害,其血清、脑组织中MDA、N0、NOS含量明显上升、SOD含量明显下降,两组比较有显著性差异(均P<0.01);与再灌注组比,预防组病理改变较轻,其血清、脑组织中MDA、NO、NOS明显下降,SOD明显上升,两组比较均有显著性差异(分别P<0.01和P<0.05)。结论 西比灵可减少自由基,诱导SOD生成,具有保护脑细胞的作用。     

Effects of transection of cervical sympathetic trunk on cerebral infarct volume and oxygen free radical levels in rats with focal cerebral ischemia/reperfusion injury

BACKGROUND: Stellate ganglion block (SGB) plays a protective role on the brain, but the precise mechanism of action is not clear.OBJECTIVE: To simulate SGB by transection of the cervical sympathetic trunk (TCST) and to investigate the TCST effects on changes in cerebral infarct volume and oxygen free radical levels in rats with focal cerebral ischemia/reperfusion injury.DESIGN, TIME AND SETTING: A complete randomized control animal experiment was performed at the Institute of Neurological Diseases of Taihe Hospital, Yunyang Medical College from February to December 2005.MATERIALS: A total of 101 healthy Wistar rats, weighing 280-320g, of both genders, aged 17-18 weeks, were used in this study. 2,3,5-triphenyltetrazolium chloride (TTC) was purchased from Changsha Hongyuan Biological Company. Superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) assay kits were provided by Nanjing Jiancheng Bioengineering Institute.METHODS: Rats were randomly divided into a TCST group, a model group and a sham operation group. Successful models were included in the final analysis, with at least 20 rats in each group. After TCST, rat models of focal cerebral ischemia/reperfusion injury were established in the TCST group by receiving middle cerebral artery occlusion (MCAO) by the intraluminal suture method for 2 hours, followed by 24 hours of reperfusion. Rat models of focal cerebral ischemia/reperfusion injury were made in the model group. Rats in the sham operation group underwent experimental procedures as for the model group, threading depth of 10mm, and middle cerebral artery was not ligated.MAIN OUTCOME MEASURES: Brain tissue sections of ten rats from each group were used to measure cerebral infarct volume by TTC staining. Brain tissue homogenate of another ten rats from each group was used to detect SOD activities, MDA contents and NO levels. Rat neurological function was assessed by neurobehavioral measures.RESULTS: Cerebral infarct volume was bigger in the model group than in the TCST group (P<0.05). Twenty four hours after cerebral ischemia/reperfusion, SOD activities were lower, whereas MDA contents and NO levels were higher in the TCST and model groups, compared with the sham operation group (P<0.05 or P<0.01). Compared with the model group, SOD activities were higher, whereas MDA contents and NO levels were lower in the TCST group (P<0.05).CONCLUSION: After TCST, cerebral infarct volume is reduced, SOD activities are increased, and MDA contents and NO levels are decreased compared to the model group in rats with focal cerebral ischemia/reperfusion injury. These changes may be associated with TCST.     

Effects of transection of cervical sympathetic trunk on cerebral infarct volume and oxygen free radical levels in rats with focal cerebral ischemia/reperfusion injury*★

BACKGROUND： Stellate ganglion block （SGB） plays a protective role on the brain, but the precise mechanism of action is not clear. OBJECTIVE： To simulate SGB by transection of the cervical sympathetic trunk （TCST） and to investigate the TCST effects on changes in cerebral infarct volume and oxygen free radical levels in rats with focal cerebral ischemia/reperfusion injury. DESIGN, TIME AND SETTING： A complete randomized control animal experiment was performed at the Institute of Neurological Diseases of Taihe Hospital, Yunyang Medical College from February to December 2005. MATERIALS： A total of 101 healthy Wistar rats, weighing 280-320 g, of both genders, aged 17-18 weeks, were used in this study. 2, 3, 5-triphenyltetrazolium chloride （TTC） was purchased from Changsha Hongyuan Biological Company. Superoxide dismutase （SOD）, malondialdehyde （MDA） and nitric oxide （NO） assay kits were provided by Nanjing Jiancheng Bioengineering Institute. METHODS： Rats were randomly divided into a TCST group, a model group and a sham operation group. Successful models were included in the final analysis, with at least 20 rats in each group. After TCST, rat models of focal cerebral ischemia/reperfusion injury were established in the TCST group by receiving middle cerebral artery occlusion （MCAO） by the intraluminal suture method for 2 hours, followed by 24 hours of reperfusion. Rat models of focal cerebral ischemia/reperfusion injury were made in the model group. Rats in the sham operation group underwent experimental procedures as for the model group, threading depth of 10 mm, and middle cerebral artery was not ligated. MAIN OUTCOME MEASURES： Brain tissue sections of ten rats from each group were used to measure cerebral infarct volume by TTC staining. Brain tissue homogenate of another ten rats from each group was used to detect SOD activities, MDA contents and NO levels. Rat neurological function was assessed by neurobehavioral measures. RESULTS： Cerebral infarct volume was bigger in the     

L-NAME对大鼠局灶性脑缺血灌注损伤Fos蛋白表达的影响

目的观察一氧化氮含量的变化对缺血再灌注损伤后Fos蛋白表达的影响。方法采用线拴法制作大鼠局灶性脑缺血再灌注损伤模型,利用NADPH组化和Fos蛋白免疫组化双标技术研究NOS抑制剂L－NAME对大鼠局灶性脑缺血再灌注损伤脑皮层Fos蛋白表达的影响。结果缺血60min再灌注3h后损伤侧脑组织皮质一氧化氮合酶阳性神经元较正常增多并深染,Fos蛋白表达增加,L－NAME（3mg／kg）治疗组脑皮质神经元Fos蛋白的表达量较对照组减少,L－NAME（10mg/kg）治疗组脑皮质神经元Fos蛋白的表达量较对照组明显减少,同时也可见给予L－NAME后脑组织皮质内NOS阳性神经元无论在数量上还是在细胞着色、胞体突起均明显减少。结论c－fos基因表达也可能部分参与了NO的致神经细胞损伤过程。     

大鼠急性局灶性脑缺血再灌注脑组织NO含量和NOS活性的变化

目的探讨一氧化氮（ＮＯ）和神经元型ＮＯ合酶（ｎＮＯＳ）是否参与急性局灶性脑缺血再灌注的发病机理。方法采用栓红法建立大鼠大脑中动脉阻塞（ＭＣＡＯ）模型,观察脑组织ＮＯ含量和一氧化氮合酶（ＮＯＳ）活性的变化及ｎＮＯＳ抑制剂７－硝基吲唑（７－ＮＩ）对再灌注期两者的影响。结果缺血３０分种ＮＯ含量和ＮＯＳ活性显著升高,缺血３小进两者下降;再灌注３０分种ＮＯＴ和ＮＯＳ再次升高,而再灌注３小时两者又下降。７－Ｎ     

川芎嗪对脑挫伤大鼠脑组织MDA、SOD、NO及含水量影响的研究

目的 观察川芎嗪对脑挫伤大鼠脑组织中丙二醛（MDA）、超氧化物歧化酶（SOD）、一氧化氮（NO）含量及脑组织含水量的影响，探讨川芎嗪在治疗脑挫伤中的应用。方法 建立自由落体大鼠脑挫伤模型，治疗组脑挫伤后第2天开始应用川芎嗪腹腔注射治疗，对照组腹腔注射等量生理盐水．连续应用6d。正常组不致伤。检测治疗组、对照组及正常组大鼠脑组织中MDA、SOD、NO含量及脑组织含水量，并进行统计分析。结果 脑挫伤后大鼠脑组织中MDA、NO含量及脑组织含水量较正常组增高，SOD含量较正常组降低（P〈0．05）。川芎嗪治疗组大鼠脑组织中MDA、NO含量及脑组织含水量较对照组显著降低，SOD含量较对照组显著上升（P〈0．05）。结论 川芎嗪能够有效提高挫伤后脑组织中SOD含量，减少MDA及NO含量产生．有效改善脑水肿，从而发挥治疗作用。     

脑缺血对局部超氧化物岐化酶、丙二醛水平的影响

建立大鼠右大脑中动脉栓塞（ＲｉｇｈｔＭｉｄｄｌｅＣｅｒｅｂｒａｌＡｒｔｅｒｙＯｃｌｕｓｉｏｎＲ－ＭＣＡＯ）模型,检测局部缺血后不同时间左右脑组织超氧化物岐化酶（ＳｕｐｅｒｏｘｉｄｅＤｉｓｍｕｔａｓｅＳＯＤ）、丙二醛（ＭＤＡ）的含量,发现Ｒ－ＭＣＡＯ１０分钟始,缺血脑组织ＳＯＤ即降低,至３０分钟后恢复,而ＭＤＡ则在Ｒ－ＭＣＡＯ６０分钟后持续升高。说明缺血后ＳＯＤ活力下降、致ＭＤＡ蓄积,是造成脑组织损伤的机制之一。     

缺血预处理对大鼠局灶性脑缺血的保护作用

目的 探讨缺血预处理对大鼠局灶性脑缺血的保护作用及其机制。方法 将30只雄性SD大鼠随机分为假手术组、缺血组和缺血预处理组,每组10只。使用改良线栓法制作大鼠局灶性脑缺血模型。采用Longa-Bederson（LB）评分法评估缺血预处理对大鼠局灶性脑缺血后神经功能的影响,采用TTC染色方法分析大鼠海马区梗死面积,采用TUNEL染色法分析大鼠海马区细胞凋亡,使用气相色谱方法分析缺血预处理后大鼠海马区域丙酮酸含量。结果 缺血预处理组大鼠LB评分[（1.67±0.21）分}明显优于缺血组[（3.17±0.31）分;P<0.05]。缺血预处理组大鼠海马区梗死面积[（154±8.1）mm2]明显少于缺血组[（221.20±5.86）mm2;P<0.05]。缺血预处理组大鼠海马区域丙酮酸含量[（3.70±0.20）μmol/g]明显高于缺血组[（2.58±0.17）μmol/g;P<0.05]。结论 缺血预处理对大鼠局灶性脑缺血具有显著神经保护作用,其机制可能与明显减少大鼠脑组织梗死、增加海马丙酮酸含量、减少细胞凋亡有关。     

Effects of Lamotrigine on brain nitrite and cGMP levels during focal cerebral ischemia in rats

Glutamate receptor antagonists are protective in animal models of focal cerebral ischemia. Lamotrigine (3,5-diamino-6-[2,3-dichlorophenyl]-1,2,4-triazine) is an anticonvulsant drug that blocks voltage-gated sodium channels and inhibits the ischemia-induced release of glutamate. Experiments in primary neuronal cultures implicate nitric oxide (NO) as a mediator of glutamatergic neurotoxicity acting via N-Methyl- d -Aspartate (NMDA) receptors. The effect of glutamate release inhibitor, Lamotrigine upon NO and cGMP production has been examined in focal cerebral ischemia in rats. Focal cerebral ischemia was produced by the permanent occlusion of right middle cerebral artery (MCA) in urethane anesthetized rats. A number of indicators of brain NO production (nitrite, cGMP) were determined in ipsilateral and contralateral cerebral cortex and cerebellum after 0, 10, 60 min of focal cerebral ischemia. The same parameters were measured in rats treated with Lamotrigine (20 mg/kg, i.p.) 30 min before or just after the occlusion of the right MCA.