V1a受体拮抗剂对脑出血大鼠水孔蛋白-4表达的影响及血脑屏障通透性的研究

目的研究血管加压素1a受体(V1aR)拮抗剂对脑出血(in tracerebra l hem orrhage,ICH)后水孔蛋白-4(aquaporin-4,AQP 4)表达及血脑屏障(BBB)通透性的影响。方法运用立体定向技术,尾动脉采血制作大鼠脑出血模型。模型制作成功后,治疗组侧脑室注射V1aR拮抗剂,对照组仅注射等量人工脑脊液。采用免疫组化技术对血肿周围组织AQP 4蛋白进行检测。通过检测渗出到脑血管外的伊文斯蓝(Evans B lue,EB)的含量来定量观察BBB的通透性。结果脑出血后6h尾壳核血肿周围组织AQP 4蛋白表达开始增高,在脑出血1d达高峰(P<0.01),持续到3d以后逐渐下降,到7d仍高于正常水平。而用V1aR拮抗剂脑室注射后,AQP 4蛋白表达在各时间点表达明显降低。BBB通透性在脑出血后6h开始升高,1d达高峰(P<0.01),3d后回落,侧脑室注入V1aR拮抗剂后,BBB通透性与对照组比较明显下降(P<0.05)。结论V1aR拮抗剂能抑制AQP 4蛋白的表达,保护BBB,减轻脑出血后脑水肿。     

实验性脑出血血肿周围脑组织基质金属蛋白酶组织抑制剂-1的表达及其与脑水肿的关系

目的探讨实验性脑出血(ICH)血肿周围脑组织基质金属蛋白酶组织抑制剂-1(TIMP-1)的表达及其与脑水肿的关系。方法采用自体血注入法建立大鼠ICH模型,制模后1h、3h、6h、12h、24h、36h、48h、72h、7d共9个时间点分别用干湿重法测血肿周围脑组织含水量,伊文思蓝(EB)检测血-脑屏障(BBB)通透性,Western Blot方法检测血肿周围组织的TIMP-1的表达;分析三者间的关系,并与假手术组相比较。结果与假手术组比较,ICH后各时间点血肿周围脑组织含水量和EB含量均明显增加(P<0.05～0.01),均于ICH48h达到高峰,且二者呈正相关(r=0.940,P<0.01);TIMP-1在ICH12～36h表达明显减低,ICH1～24h TIMP-1表达量与脑组织含水量以及EB含量呈负相关(r=-0.922,-0.950,均P<0.05)。结论大鼠ICH后血肿周围脑组织TIMP-1表达下调,可能促进了ICH早期的脑水肿形成。     

内皮屏障抗原在实验性大鼠脑出血后的表达及其与血脑屏障通透性改变的关系

目的 探讨内皮屏障抗原(EBA)在脑出血(ICH)后血肿周围脑组织中的表达及其在ICH后血脑屏障(BBB)通透性改变中的作用.方法 利用立体定向技术向大鼠尾状核内注入50μl自体股动脉血建立ICH模型,用免疫组化法检测ICH后血肿周围EBA、纤维蛋白原的蛋白表达、Belayev法测定BBB通透性及干湿重法测定脑水含量的动态变化.结果 ICH后6hEBA表达开始减少,3d时最少,7d略有回升;纤维蛋白原表达、BBB通透性、脑水含量均于ICH后6h开始升高,3d达高峰,7d逐渐下降,ICH后EBA蛋白表达与脑水含量呈负相关(r=-0.840,P＜0.01),与EB含量负相关(r=-0.827,P ＜0.01),与纤维蛋白原表达呈负相关(r=-0.851,P＜0.01).结论 大鼠实验性ICH后EBA的表达减少,且与纤维蛋白原、BBB通透性及脑水含量增高具有明显的相关性.     

大鼠脑出血周边组织脑水含量、细胞凋亡和Bax表达的变化及粒细胞集落刺激因子的影响

目的研究粒细胞集落刺激因子(G-CSF)对脑出血(ICH)大鼠神经功能损伤、脑水肿的影响,粒细胞集落刺激因子对大鼠脑出血周边组织Bax表达及细胞凋亡的影响。方法 Wistar大鼠112只,随机分为脑出血组、脑出血+G-CSF组,两组各分为(出血前、出血后4 h、6 h、12 h、24 h、72 h、7 d)7个时间点。免疫组化法测定大鼠脑出血周边组织Bax的表达,利用原位末端标记法测定出血周边组织中神经细胞的凋亡情况。并在脑出血后24 h、48 h、72 h、7 d测定大鼠神经功能评分和脑含水量。结果脑出血后24 h开始大鼠就出现明显的神经功能缺失症状,G-CSF治疗后神经功能缺失症状得到明显改善,在1 w内的各个时间点两组比较差异有显著性(P<0.01)。脑出血大鼠24 h即出现脑水肿,脑水肿形成的高峰时间在ICH后48 h~7 d左右,ICH大鼠在G-CSF治疗后脑水肿形成明显减轻,两组间比较差异有显著性(P<0.05;P<0.01)。大鼠脑出血周边组织Bax表达4 h开始升高(P<0.01),大约24 h左右Bax表达达峰值。大鼠脑出血周边组织6 h出现凋亡细胞,12 h上升显著(P<0.01),3 d达峰值,7 d时仍存在较多凋亡细胞。G-CSF干预后,Bax表达及凋亡细胞数量与脑出血组对应时间点比较显著下降(P<0.01)。结论脑出血大鼠出现明显脑水肿和神经功能损伤,脑出血周边组织神经细胞存在长时间凋亡。G-CSF可抑制大鼠脑出血后Bax蛋白表达,从而抑制神经细胞凋亡。     

去铁胺干预对大鼠脑出血后水通道蛋白4 mRNA表达及脑水含量的影响

目的观察水通道蛋白4(AQP4)及脑水含量在脑出血模型组及去铁胺(DFO)模型干预组的动态变化。以期阐明AQP4及DFO在脑出血后水肿形成中的机制及作用。方法采用自体血脑出血模型,应用RT-PCR方法观察AQP4mRNA的表达,干湿重法测量血肿周围的脑水含量。结果 AQP4 mRNA表达在ICH各组及DFO干预3d、7d组较假手术组明显增高,且以第3天最高。DFO干预各组与同期ICH组相比AQP4mRNA表达显著降低, DF0干预第14天组AQP4 mRNA表达与对照组无差别。脑水含量显示在ICH第1、3、7天组及DFO干预3d组较假手术组明显增高,且以第3天最高;ICH 14d组及DF0干预第7天、第14天组均与正常组无差别;DFO干预第3天及第7天组较ICH组同期脑水含量显著减少。相关分析显示AQP4mRNA表达及脑水含量之间存在正相关关系。结论 AQP4在脑出血后水肿形成及消退中可能起重要作用,去铁胺可能为干预脑出血后水肿形成的有效手段。     

大鼠脑出血后水通道蛋白4的表达与血脑屏障超微结构变化的相关性研究

目的观察脑出血后水通道蛋白4(AQP4)和血脑屏障(BBB)超微结构在脑水肿形成中的不同时间点的变化特征,探讨二者在脑水肿形成中的作用机制。方法采用自体非抗凝血注入尾状核制做脑出血模型,免疫组化法检测脑出血后血肿周围组织AQP4的表达,伊文思蓝检测BBB的通透性,干湿重法检测脑水肿含水量,电镜观察BBB超微结构的变化。结果与对照组相比较,脑出血组在脑出血后6h脑含水量、AQP4表达和伊文思蓝含量开始增加,差异有显著性(P<0.05),72h达到最高峰(P<0.05),之后开始下降,到第7天仍高于正常。AQP4表达与BBB通透性呈显著正相关(r=0.726,P<0.05);AQP4表达与脑含水量的变化规律也趋于一致(r=0.793,P<0.05)。BBB电镜观察:脑出血后6h脑微血管内皮细胞吞饮小泡增多、线粒体堆积。72h胶质细胞足突内线粒体逐渐肿胀、模糊,细胞充满大量空泡,基膜断裂。7d内皮细胞回缩,毛细血管基底膜形态开始恢复。结论脑出血后AQP4表达和BBB的通透性有显著相关性,提示脑出血后可能通过提高AQP4的表达水平,增加BBB的通透性,参与脑水肿的形成。     

G-CSF对脑出血大鼠血肿周围血管新生的作用机制研究

目的观察粒细胞集落刺激因子(G-CSF)对脑出血(ICH)大鼠血肿周围血管新生的影响,并探讨其机制。方法 63只SD大鼠随机分为假手术组、ICH组、治疗组,每组21只。利用立体定位仪,向SD大鼠右侧苍白球注入断尾获取的自体动脉血制备ICH模型,治疗组于造模1 h后腹腔注射重组G-CSF60μg/kg,假手术组、ICH组经腹腔注射等量等渗盐水。3组大鼠于术后6 h、24 h、48 h、72 h、7 d、14 d、21 d进行神经功能障碍评分,后处死大鼠,免疫组化检测血肿周围CD34+血管数、VEGF的表达。结果治疗组大鼠从24 h开始各时间点神经功能障碍评分较ICH组明显增加(P<0.05)。假手术组见少许CD34+血管表达;ICH组6 h开始CD34+血管表达增多,14 d达高峰;治疗组各时间点CD34+血管表达较ICH组明显增多(P<0.05),高峰提前至7 d。假手术组见少量VEGF表达;ICH组6 h即出现VEGF表达增多,7¹4 d达高峰;治疗组各时间点VEGF表达较ICH组明显增多(P<0.05),高峰提前至72 h14 d达高峰;治疗组各时间点VEGF表达较ICH组明显增多(P<0.05),高峰提前至72 h⁷ d。结论 G-CSF可上调ICH后VEGF表达,增加血肿周围新生血管生成,改善神经功能。     

大鼠实验性脑出血后血肿周围水通道蛋白-4动态变化的研究

目的研究大鼠脑出血后血肿周围水通道蛋白4(AQP4)的动态变化及其与脑水肿、脑损伤程度的关系。方法采用SD大鼠自体动脉血注入尾状核建立脑出血模型,应用免疫组织化学法、干湿重法、Alexis法分别检测大鼠脑出血后不同时间点血肿周围AQP4、脑组织含水量及神经功能缺损程度的动态变化。结果①血肿周围AQP4在脑出血后12h表达开始增强,1～3d达到高峰,7d后略高于正常,14d基本恢复正常。②脑组织含水量在出血后6h增加,1～3d达到峰值,7d明显减轻,14d基本恢复正常。③神经功能缺损从出血后6h开始,最重的时间点是12h～3d,7d明显减轻,14d基本恢复正常。④脑出血后血肿周围AQP4的表达与脑组织含水量之间存在关联(x2mh=16.49,P<0.05)。⑤脑出血后血肿周围AQP4的表达与神经功能缺损程度之间存在关联(x2mh=15.07,P<0.05)。结论①AQP4的表达与脑水肿、脑损伤的发生发展密切相关,是引起出血性脑水肿脑损伤的重要因素之一。②早期积极控制脑出血后AQP4的过度表达将是减轻和预防脑出血后脑水肿脑损伤的有效途径。     

大鼠脑出血周边组织谷氨酸、脑水含量和细胞凋亡的变化及碱性成纤维生长因子的影响

目的研究碱性成纤维生长因子(bFGF)对脑出血(ICH)大鼠神经功能损伤、脑水肿的影响,碱性成纤维生长因子对大鼠脑出血周边组织谷氨酸(Glu)含量及细胞凋亡的影响。方法 Wistar大鼠112只,随机分为脑出血组、脑出血+bFGF组,两组各分为(出血前、出血后4h、6h、12h、24h、72h、7d)7个时间点。利用化学方法测定大鼠脑出血周边组织Glu含量,利用原位末端标记法测定出血周边组织神经细胞的凋亡情况。并在脑出血后24h、48h、72h、7d测定大鼠神经功能评分和脑含水量。结果脑出血后24h开始大鼠就出现明显的神经功能缺失症状,bFGF治疗后神经功能缺失症状得到明显改善,在1w内的各个时间点两组比较差异有显著性(P<0.01)。脑出血大鼠24h即出现脑水肿,脑水肿形成的高峰时间在ICH后48h～7d左右,ICH大鼠在bFGF治疗后脑水肿形成明显减轻,两组间比较差异有显著性(P<0.05;P<0.01)。大鼠脑出血后4h血肿周边脑区Glu含量开始升高(P<0.01),在血肿形成的高峰期12h达峰值。大鼠脑出血周边组织6h出现凋亡细胞,12h上升显著(P<0.01),3d凋亡细胞达峰值,7d时仍存在较多凋亡细胞。bFGF干预后Glu含量及凋亡细胞数量与脑出血组对应时间点比较显著下降(P<0.01)。结论脑出血大鼠出现明显脑水肿和神经功能损伤,脑出血周边组织Glu含量增高,神经细胞存在长时间凋亡,Glu可以促其凋亡;bFGF干预后,大鼠神经功能改善,脑水肿减轻,Glu含量降低,bFGF减少大鼠脑出血周边组织神经细胞凋亡。     

脑出血大鼠血肿周围白介素-10的表达及其与脑水肿的相关性

目的 探讨脑出血(ICH)大鼠血肿周围白介素-10(IL-10)的表达及其与脑水肿的相关性.方法 130只SD大鼠随机分为正常对照组、假手术组和ICH组;应用肝素化Ⅶ型胶原酶建立大鼠ICH模型;制模后12 h、24 h、48 h、72 h、7 d及14 d应用Bederson量表评定神经功能缺损程度,干/湿重法测定脑组织含水量,免疫组化方法检测脑组织血肿周围IL-10的表达.结果 (1)ICH组大鼠神经功能缺损评分与脑组织含水量均在ICH 12 h升高,48 h达高峰,7 d后恢复正常.(2)ICH组脑组织IL-10表达ICH 12 h明显升高,14 d达高峰,各时间点间均显著高于正常对照组和假手术组(P＜0.05～0.01).(3)ICH组神经功能缺损评分与脑组织含水量呈正相关(r=0.761,P＜0.01),脑组织IL-10表达与脑组织含水量、神经功能缺损评分呈负相关(r=-0.65,-0.753,均P＜0.01).结论 ICH大鼠血肿周围脑组织IL-10表达逐渐升高,可能参与了ICH后减轻脑水肿、促进神经功能恢复的脑保护作用.     

中药补阳还五汤对脑出血大鼠脑组织水通道蛋白4表达的影响

目的探讨中药补阳还五汤对脑出血大鼠脑组织水通道蛋白4(AQP4)表达的影响。方法 55只雄性SD大鼠随机分为假手术组(5只)、脑出血模型组(25只)和补阳还五汤治疗组(25只)。采用自体血注入法制作右侧纹状体出血大鼠模型。假手术组不注入自体血。补阳还五汤治疗组于术前给予1 ml/100 g补阳还五汤浓缩液灌胃3 d,假手术组和脑出血模型组同期给予等量生理盐水替代。在相应时间点分别对大鼠进行神经功能缺损评分后处死大鼠。采用免疫组化法检测脑组织AQP4蛋白的表达,采用原位杂交法检测脑组织AQP4 mRNA的表达。结果补阳还五汤治疗组及脑出血模型组大鼠神经功能缺损评分明显高于假手术组(均P<0.05)。补阳还五汤治疗组大鼠术后3 d和7 d时神经功能缺损评分明显低于脑出血模型组(均P<0.05)。补阳还五汤治疗组及脑出血模型组大鼠脑组织AQP4蛋白和mRNA表达水平明显高于假手术组(均P<0.05)。补阳还五汤治疗组大鼠术后3 d和7 d时脑组织AQP4蛋白和mRNA表达水平明显低于脑出血模型组(均P<0.05)。各组大鼠均未见明显不良反应。结论补阳还五汤可抑制脑出血大鼠脑组织中AQP4的表达,并有助于其神经功能恢复。补阳还五汤治疗脑出血有效可能与其抑制AQP4的表达,减轻脑水肿有关。     

钠/钙交换蛋白SLC24A6在实验性颅内出血导致脑损伤过程中的作用及机制研究

目的探究钾依赖钠/钙交换蛋白-6(SLC24A6)参与大鼠脑出血后继发性脑损伤的作用和可能机制。方法建立SD大鼠脑出血模型,检测大鼠脑出血后尾状核SLC24A6表达及其介导的细胞内钙浓度([Ca~(2+)]_i)随时间变化的情况,观察SLC24A6在正常氧浓度和低氧条件下对[Ca~(2+)]_i的调控。结果脑出血早期,尾状核SLC24A6蛋白和SLC24A6mRNA水平均降低,在脑出血后3 d降至最低水平,5和7 d后轻微升高。脑出血后早期,[Ca~(2+)]_i增加,于脑出血后3 d达最高水平,5和7 d时逐步下降。正常氧浓度下,转染SLC24A6导致HEK293[Ca~(2+)]_i升高。结论 SLC24A6通过抑制钙超载在脑出血后脑损伤中起保护作用。     

Cellular alterations produced by the experimental increase in intracellular calcium and the nature of protective effects from pretreatment with nimodipine.

The immortalized septal cell line, SN56 B5 G4, generated by the fusion of mouse septal area cells and neuroblastoma cells, was used to determine if nimodipine, an antagonist of voltage sensitive calcium 'L' channels, might act in a neuroprotective fashion when intracellular calcium levels were raised by incubation in ouabain and monensin. Fluorescent indicator dyes and the automated spectrofluorometer, the CytoFluor 2300, were used to analyze specific cellular targets and functions affected by ouabain and monensin and possible protection by prior incubation with nimodipine. Ouabain and monensin were used together to create a time- and dose-dependent toxic episode. Increases in the emission intensity of Fluo3-AM demonstrated that the concentration of intracellular calcium was monotonically increased by increasing levels of ouabain-monensin. The calcein-AM fluorescent probe indicated that there were no changes in plasma membrane permeability during the toxic episode. Lysosomal integrity decreased as indicated by decreases in neutral red retention. The concentration of free radicals increased as shown by the increase in emission intensity of 2',7'-dichlorfluorescein. Nimodipine pretreatment of the cells incubated with ouabain and monensin resulted in apparent protection of lysosomes and a reduction in the level of free radicals. While nimodipine, by itself, produced a small decrease in intracellular calcium, it actually augmented the ouabain-monensin induced increase in intracellular calcium. The data suggest that in immortalized septal cells, (a) nimodipine offers protection to certain of the responses induced by ouabain-monensin, (b) the protection offered by nimodipine may be independent of antagonism of voltage sensitive calcium channels, and (c) that the protective changes can occur at the same time that intracellular calcium is increasing. These latter observations question the hypothesis that the protection against cell death and dysfunction offered by nimodipine is due solely to maintaining calcium homeostasis.     

The influence of nimodipine, nicardipine and amlodipine on the brain free fatty acid level in rats with penicillin-induced seizures.

1. The aim of this study was to investigate the effects of the calcium channel blockers, nimodipine, nicardipine and amlodipine, on the brain free fatty acid (FFA) level in rats with chemically-induced seizures. 2. The study was carried out on Hannover-Wistar rats. Animals were anesthetized and placed in a stereotaxic apparatus. Each of them received an injection of penicillin (5000 IU/5 microliters) into the left lateral ventricle (i.c.v.). Various doses (1, 3, 10 or 30 mg/kg) of nimodipine, nicardipine or amlodipine had been injected i.p. 30 min before the penicillin application. The rats were decapitated 5 min after the occurrence of epileptic seizures. FFAs were quantified by gas chromatography using the internal standard method. 3. The results demonstrate that i.c.v. injection of penicillin was associated with significant increase in the brain FFA concentration. Tested doses of nicardipine and amlodipine did not influence the increase of the brain free palmitic, stearic, oleic and arachidonic acid level while nimodipine prevented the accumulation of free palmitic, oleic and arachidonic acid in rats with penicillin-induced seizures. Statistically insignificant decrease of steric acid was observed in animals pretreated with nimodipine. 4. It maybe assumed that the brain FFA accumulation caused by i.c.v. penicillin administration is not predominantly associated with a disturbance in calcium homeostasis via L-type voltage-sensitive calcium channels, but by some other membrane and/or intracellular mechanisms.     

人工寒潮对颈动脉粥样硬化性大鼠血压的影响

目的 探讨人工寒潮对颈动脉粥样硬化性大鼠血压的影响以及尼莫地平的干预作用.方法 将SD大鼠按随机数字表法分为正常组、假手术组和颈动脉粥样硬化组,其中颈动脉粥样硬化组再分为非寒潮组、寒潮组和干预组3个亚组,除非寒潮组外其他各组均经历人工寒潮3d,寒潮组并给予等剂量生理盐水灌胃3 d,干预组并给予尼莫地平干预,分别测量各组经历寒潮前后的血压.结果 (1)寒潮前假手术组及颈动脉粥样硬化组血压明显高于正常组,比较差异有统计学意义(P＜0.05).(2)寒潮后正常组、假手术组及寒潮组的血压较寒潮前明显增高,干预组血压较寒潮前明显下降,比较差异均有统计学意义(P＜0.05).(3)正常组、假手术组及寒潮组之间寒潮前后血压的差值比较无统计学差异.(4)与寒潮组相比,干预组的血压差值明显降低,比较差异有统计学意义(P＜0.05).结论 人工寒潮可以使正常大鼠及颈动脉粥样硬化性大鼠血压升高,尼莫地平可以预防寒潮导致的血压升高.

Abstract：

Objective To study the effect of artificial cold exposure (ACE) on the level of blood pressure in carotid atherosclerotic rats, and the prophylactic effect of nimodipine on it. Methods One hundred and thirty SD rats were randomly divided into normal group (n=10), sham-operated group (n=10), and carotid atherosclerotic (CAS) group (n=110). High-fat diet was given to the sham-operated group and CAS group; normal diet was given to the control group. Then, 105 alive rats in the CAS group were further sub-divided into non-ACE group (n=40), ACE group (n=38) and nimodipine treatment group (n=37). All the groups were subjected to ACE for 3 d except non-ACE group, and kept at 22 °C throughout the experiment. During the ACE, an intragastric administration of nimodipine was given to the nimodipine treatment group. The changes of the blood pressure before and after ACE were analyzed and compared. Results The level of pre-ACE blood pressure in the sham-operated group and CAS group was significantly higher than that in the normal group (P＜0.05). The level of post-ACE blood pressure was significantly increased in the normal group, sham-operated group and ACE group, and significantly decreased in the nimodipine treatment group as compared with the level of pre-ACE one in these groups (P＜0.05). No significant differences were noted between the levels of pre-ACE and post-ACE blood pressure in the normal group, sham-operated group and ACE group (P＞0.05). The level of post-ACE blood pressure in rats treated with nimodipine was obviously decreased as compared with that in the ACE group (P＜0.05). Conclusion ACE could increase the level of blood pressure in carotid atherosclerotic rats and this effect might be lessoned by the administration of nimodipine.     

Nimodipine ameliorates trauma-induced cochlear neuronal death

Excessive entry of Ca2+ into injured cochlear neurons activates various Ca(2+)-activated enzymes and subsequent spiral ganglion cell death. Therefore, preventing intracellular calcium overload by using Ca2+ channel antagonists may become an important countermeasure to spiral ganglion cell death. We experimentally investigated whether an L-type Ca2+ channel blocker (nimodipine) can rescue traumatized cochlear neurons from degeneration. A group of rats (n = 6) was pre-operatively treated with nimodipine for one week and compression injury was applied to the cerebellopontine angle portion of the cochlear nerve in a highly quantitative fashion. The rats from the compression with nimodipine treatment groups were post-operatively treated with nimodipine for 10 days and killed for histological examination. The histological analysis of the temporal bones revealed that the spiral ganglion cells in the basal turn of the cochlea where the magnitude of traumatic impact had been the least in our experimental condition were rescued in a statistically significant fashion in the compression with nimodipine treatment group. The results of the present study indicate that nimodipine may become an intra- and post-operative important adjunct to raise the rate of hearing preservation in vestibular schwannoma excision or other cerebellopontine angle surgical interventions.     

亚低温联合β-七叶皂甙钠对实验性脑出血后AQP4表达及脑水肿的影响

目的 研究亚低温、β-七叶皂甙钠及二者联合对大鼠实验性脑出血后AQP4表达及脑水肿的影响.方法 270只健康成年SD大鼠随机分为假手术组30只,对照组、亚低温组、β-七叶皂甙钠组及联合组各60只,每组又分为5个亚组,分别于造模后1,2,3,5,7d断头取脑,其中半数大鼠进行脑含水量测定,另一半大鼠作免疫组织化学分析.在大鼠苍白球注射胶原酶制作脑出血模型,用冰块降温及白炽灯调整与动物距离照射加温的方法调节体温,采用干湿重法观察脑水肿的变化;应用免疫组织化学方法检测脑组织AQP4表达.结果 在各个时间点脑出血模型大鼠病灶侧脑含水量及AQP4的表达均明显高于假手术组(均P＜0.01),而亚低温组、七叶组及联合组均明显低于对照组(均P＜0.05);联合组在出血后5,7d病灶侧脑含水量及AQP4的表达均低于亚低温组及七叶组(均P＜0.05); AQP4表达水平与脑含水量呈正相关(r=0.970,P＜0.01).结论 亚低温及β-七叶皂甙钠均能明显减轻大鼠脑出血后脑水肿,而二者联合可能起到协同作用;亚低温及β-七叶皂甙钠可能通过抑制AQP4的表达而减轻脑水肿.     

氯化锂预处理对脑出血后血肿周围神经细胞凋亡及核因子κB表达的抑制作用

目的 观察氯化锂预处理对大鼠脑出血后血肿周围神经细胞凋亡、炎症反应及核因子κB(NF-κB)表达的影响.方法 54只SD大鼠按随机数字表法分为假手术组、脑出血组和氯化锂预处理脑出血组,每组各18只.氯化锂预处理脑出血组手术前7 d起每天腹腔注射氯化锂(1mmol/kg).利用立体定向技术,将Ⅳ型胶原酶用微量进样器精确注入大鼠内囊诱导成脑出血模型.跟据术后处死动物的时间不同,各组再分别分为1、3、7 d三个亚组.分别采用TUNEL法、苏木素-伊红染色和免疫组织化学染色观察血肿周围神经细胞凋亡、炎症反应及NF-κB表达的情况.结果 在脑出血后1、3、7 d,与脑出血组(TUNEL阳性细胞数:18.32±3.75,33.24±6.37,20.49±4.87;NF-κB阳性细胞数:55.34±5.83,30.63±3.27,9.53±2.37)比较,氯化锂预处理脑出血组血肿周围区TUNEL阳性细胞数(15.84±3.12,10.88±4.75,5.83±4.39)明显减少,NF-κB阳性细胞数(29.27±3.37,16.36±3.64,7.64±2.31)明显降低,比较差异有统计学意义(P<0.05),炎症反应也明显减轻.结论 氯化锂预处理可能通过降低NF-κB的表达来减轻脑出血后的炎症反应,减少脑出血后血肿周围神经细胞凋亡,其对脑出血后脑损伤有神经保护作用.     

大鼠颅脑损伤后脑组织肿瘤坏死因子-α的变化及药物干预

目的探讨地塞米松、尼莫地平及血府逐瘀注射液对大鼠颅脑损伤后脑组织肿瘤坏死因子-α（TNF-α）的影响。方法将105只大鼠随机分为空白对照组（5只）,假手术组、模型组、地塞米松组、尼莫地平组、血府逐瘀组,各20只;后5组大鼠再按伤后不同时间点（伤后6h、24h、48h、96h）随机均分,每个时间点5只。采用SD大鼠打击伤模型,按相应分组使用地塞米松、尼莫地平和血府逐瘀注射液进行干预,采用免疫组化法检测打击伤后各时间点TNF-α的表达情况。结果造模后各组大鼠脑组织中TNF-α的表达水平均显著高于空白对照组（P〈0.01）。在致伤后48h内,地塞米松组TNF-α的表达较模型组稍低,差异无统计学意义（P〉0.05）;在伤后96h,地塞米松组TNF-α的表达较模型组明显下降（P〈0.01）。在不同时间点,血府逐瘀组与尼莫地平组TNF-α表达均较模型组明显下降（P〈0.01）。血府逐瘀组TNF-α表达量最低,与尼莫地平组和地塞米松组比较,差异显著（P〈0.01）。结论地塞米松的作用具有迟发性,在颅脑损伤早期不能减轻炎症反应而在晚期能减少TNF-α的产生。尼莫地平与血府逐瘀注射液均可减轻颅脑损伤后的继发性炎症反应,且血府逐瘀注射液的效果强于尼莫地平。     

Effect of nimodipine on cerebral blood flow and metabolism in rats during hyperventilation

Nimodipine shws promise in the prevention and treatment of brain ischemia. We examined the interaction of nimodipine pretreatment in a dose sufficient to prevent postischemic hypoperfusion and hyperventilation. We studied four groups of rats: normocarbia plus vehicle (Group 1, n = 5), hypocarbia plus vehicle (Group 2, n = 4), normocarbia plus nimodipine (Group 3, n = 7), and hypocarbia plus nimodipine (Group 4, n = 6). Groups 3 and 4 received 1 mg/kg i.p. nimodipine, and Groups 1 and 2 received an equivalent amount of vehicle. Ventilation was left unaltered in Groups 1 and 3 or increased to lower PaCO2 to 21-24 mm Hg in Groups 2 and 4. Determination of regional cerebral glucose utilization (rCGU) was carried out using the [3H]2-deoxyglucose method, and regional cerebral blood flow (rCBF) was determined by the indicator fractionation method using [14C]iodoantipyrine. The brain regions studied were the cerebral hemispheres, the diencephalon, the cerebellum, and the brainstem. Hyperventilation in Groups 2 and 4 from approximately 38 to 22 mm Hg reduced rCBF to 60% of normocarbic levels (p less than 0.05). The slope and intercept of this response were similar in vehicle- and nimodipine-pretreated rats. Nimodipine modestly decreased mean arterial blood pressure by 20% and increased plasma glucose concentration by 60% (p less than 0.05). Although nimodipine tended to increase rCBF and decrease regional cerebrovascular resistance (rCVR), this was significant only for hemispheric rCVR (p less than 0.05). There was a borderline effect for nimodipine to increase rCGU, especially during hypocarbia.(ABSTRACT TRUNCATED AT 250 WORDS)