亚低温对局灶性脑缺血大鼠血清白细胞介素和缺血局部细胞间黏附分子-1表达的影响

目的观察亚低温对局灶性脑缺血大鼠缺血局部细胞间黏附分子-1（ICAM-1）表达和血清白细胞介素-6（IL-6）含量的影响，探讨亚低温对脑缺血性损害的神经保护作用机制。方法将30只体质量在250-300g的雌性Sprague—Dawley大鼠随机分为亚低温组（n=151和对照组（n=15），采用线栓法阻断大鼠一侧大脑中动脉制作局灶性脑缺血模型，制模成功后，将亚低温组和对照组大鼠分别置于冰毯机和常温操作台上，使其肛温保持在（33±1）℃和（37±0．5）℃。12h后，自左心室取血，断头取脑，采用免疫组化方法检测缺血区ICAM-1阳性血管数目和应用免疫放射测定法（IRMA）检测血清IL-6含量。结果免疫组化分析示缺血局部ICAM-1的表达较对照组下降，IRMA检测的血清IL-6含量亚低温组较对照组降低。结论亚低温可降低局灶性脑缺血大鼠血清IL-6含量和减少缺血局部ICAM—1的表达，推测亚低温降低IL-6和ICAM—1的表达为亚低温减轻脑缺血性损害的神经保护作用之一。     

不同类型缺血性卒中患者血管反应性比较

目的 探讨不同类型缺血性卒中患者的脑血管反应性，为卒中二级预防中血压水平的调控提供理论依据。方法 选取症状性大脑中动脉粥样硬化性狭窄（MCAS）患者70例（32例为双侧MCAS患者），腔隙性脑梗死患者30例，年龄、性别相匹配的健康人36例为对照组。采用经颅多普勒（TCD）超声检测屏气前、屏气末双侧大脑中动脉（MCA）血流速度，计算屏气指数（BHI）。结果 症状性MCAS患者病灶侧、非病灶侧病变MCA的BHI均明显低于健康对照组（0.91±0.43&#8197;vs&#8197;1.53±0.80；1.24±0.42&#8197;vs&#8197;1.53±0.80，P均<0.01），病灶侧MCA的BHI明显低于非病灶侧（0.91±0.43&#8197;vs&#8197;1.24±0.42）；腔隙性脑梗死患者BHI明显低于健康对照组（1.28±0.86&#8197;vs&#8197;1.53±0.80，P<0.05）。症状性MCAS患者中，重度狭窄组BHI明显低于轻、中度狭窄组（0.65±0.36&#8197;vs&#8197;1.41±0.59；0.65±0.36&#8197;vs&#8197;1.11±0.42，P均＜0.05）。结论 症状性MCAS及腔隙性脑梗死患者的脑血管反应性均存在不同程度的受损，检测其脑血管反应性有助于卒中二级预防中血压水平的调控。     

重症脑血管病患者早期气管切开的临床价值

目的 &#8197;探讨重症脑血管病患者早期气管切开的临床价值。方法 回顾性分析102例重症脑血管病患者。所有患者入院48&#8197;h内进行了气管插管，气管插管后5&#8197;d内进行了气管切开者55例（早期气管切开组）；气管插管5&#8197;d后进行了气管切开者47例（延迟气管切开组）。比较两组间病死率、镇静药物的用量、院内获得性肺炎（HAP）的发生率、机械通气的时间、ICU住院时间等指标。结果 早期气管切开组机械通气的时间、ICU住院时间、抗生素使用天数和镇静剂的用量均低于延迟气管切开组，差异有统计学意义[（177±94）h&#8197;vs（266±162）h，P=0.03；（10±5）d&#8197;vs（13±4）d，P=0.006；（9±4）d&#8197;vs（12±4）d，P=0.03；（139±39）mg&#8197;vs（186±48）mg，P=0.001）]。两组病死率和HAP的发生率差异无统计学意义（29.1%&#8197;vs&#8197;36.2%，P=0.45；49.1%&#8197;vs&#8197;63.8%，P=0.13）。结论 重症脑血管病患者早期气管切开可获得较大的收益，提倡早期气管切开以改善预后。     

三七通舒胶囊对局部脑缺血大鼠模型海马内白细胞介素-1β、细胞问粘附分子-1表达的影响

目的研究三七通舒胶囊对局部脑缺血模型海马内白细胞介素-1β（IL-1β）、细胞间粘附分子-1（ICAM-1）表达水平的影响。方法将90只大鼠随机分成三七通舒胶囊药物组,生理盐水组和假手术对照组,每组30只。制作大鼠大脑中动脉栓塞（MCA0）模型,分别在缺血0．5,3,12,24,120h后断头处死,用ELISA法检测缺血脑组织海马区IL-1β、ICAM-1的含量。结果药物组与生理盐水组中IL-18和ICAM-1的含量在各时相点均明显高于对照组（P〈0．05）,对照组在各时相点IL-1β、ICAM-1的含量无变化,而生理盐水组在各时相点IL-1β、ICAM-1均高于药物组（P〈0．05）。结论局部脑缺血海马内IL-1β及ICAM-1表达增多,三七通舒胶囊可降低缺血脑组织内IL-1β、ICAM-1表达水平。     

低分子肝素治疗短暂性脑缺血发作的疗效观察

目的 探讨在抗血小板治疗基础下加用低分子肝素对短暂性脑缺血发作（TIA）的治疗效果。方法 对102例TIA患者进行前瞻性非随机对照研究。对照组54例，给予控制危险因素、阿司匹林50&#8197;mg、奥扎格雷钠160&#8197;mg，疗程7～10&#8197;d；治疗组48例，在上述治疗的基础上加用低分子肝素钠5000&#8197;U，每日两次脐周皮下注射，疗程7～10&#8197;d。两组在年龄、性别、分型（颈内动脉系统或椎基底动脉系统）、危险因素、每次症状持续时间以及到治疗时的发病次数均无统计学差异。结果 药物治疗30&#8197;d内，两组的疗效无统计学差异（Ｐ＞0.05）。随访3个月的结果示：两组间的卒中复发率（包括TIA、脑梗死）、心肌梗死发生率无统计学差异（Ｐ＞0.05）。治疗组2例齿龈出血，对照组无出血发生。结论 在抗血小板治疗基础上，加用低分子肝素未改善TIA治疗效果。     

硫辛酸对氧化低密度脂蛋白诱导的大鼠胸主动脉血管平滑肌细胞增殖的影响

目的 探讨抗氧化剂硫辛酸（lipoic acid，LA）对氧化低密度脂蛋白（ox-LDL）引起的大鼠主动脉血管平滑肌细胞（VSMC）增殖的影响及其机制。方法 将培养的大鼠主动脉平滑肌细胞分成5组：对照组、ox-LDL组及LA三个浓度干预组（20、80和100&#8197;mg/L）。MTT比色法测定VSMC增殖程度，生化法测定丙二醛（MDA）及一氧化氮（NO）含量。结果 与对照组相比，ox-LDL组大鼠主动脉VSMC增殖明显，MDA水平升高，NO水平降低，差异均有统计学意义（P<0.05～0.01）。与ox-LDL组比较，LA各浓度干预组（20、80和100&#8197;mg/L）大鼠主动脉VSMC增殖受到抑制，MDA水平下降，NO水平升高，差异均有统计学意义（P均<0.05）。LA各浓度干预组间VSMC增殖程度、MDA和NO水平差异亦有统计学意义（P<0.05）。结论 LA对ox-LDL引起的大鼠主动脉VSMC的增殖有抑制作用，而且可同时使细胞内MDA减少及NO含量增加，从而有可能延缓动脉粥样硬化的发生发展过程。     

茶氨酸对大鼠局灶性脑缺血性损伤后炎性细胞因子表达的影响

目的研究茶氨酸对局灶性脑缺血性损伤后大鼠脑组织肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、细胞间粘附分子-1（ICAM-1）以及单核细胞趋化蛋白-1（MCP-1）含量的影响,以探讨其减轻脑缺血性损伤的机制。方法健康雄性SD大鼠36只,按随机数字表随机分为假手术组、脑缺血组和实验组（脑缺血前1h腹腔注射茶氨酸）,采用线栓法建立大鼠大脑中动脉栓塞模型。采用放射免疫法测定脑组织TNF-α、IL-6含量,酶联免疫吸附法检测脑组织ICAM-1及MCP-1含量。结果与假手术组相比,脑缺血组大鼠脑组织TNF-α、IL-6、ICAM-1及MCP-1含量明显升高（P〈0.05）,茶氨酸可以明显地抑制缺血脑组织中上述细胞因子含量的增加（P〈0.05）。结论茶氨酸可抑制大鼠局灶性脑缺血再灌注早期炎性细胞因子的表达,对缺血脑组织具有保护作用。     

亚低温对大鼠局灶性脑缺血ICAM-1和TNF-α表达的影响

目的:脑缺血后ICAM-1和TNF-α的表达增加。降低ICAM-1和TNF-α的表达和亚低温对缺血性脑卒中具有神经保护作用。本研究的目的在于观察亚低温对大鼠局灶性脑缺血ICAM-1和TNF-α表达的影响,并探讨亚低温对脑缺血性损害的神经保护作用机制。方法:采用栓线法阻断大鼠一侧大脑中动脉制作局灶性脑缺血动物模型,设实验组和对照组,分别置于冰毯机上和常温操作台上,使其肛温分别保持在34℃±0.5℃和37℃±0.5℃。12h后断头取脑,采用免疫组化方法检测缺血区ICAM-1阳性血管数目和采用双抗夹心酶联免疫吸附法(ELISA)测定血清TNF-α水平。结果:实验组ICAM-1和TNF-α的表达较对照组下降。结论:亚低温可降低大鼠局灶性脑缺血的ICAM-1和TNF-α的表达,推测亚低温降低ICAM-1和TNF-α的表达为亚低温减轻脑缺血性损害的神经保护作用机制之一。     

硫辛酸对氧化低密度脂蛋白诱导平滑肌细胞脂质堆积的影响

目的 观察硫辛酸（LA）对氧化低密度脂蛋白（ox-LDL）诱导的大鼠胸主动脉平滑肌细胞（VSMC）内甘油三脂(TG)、总胆固醇(TC)、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-PX）活性的影响。方法 选取SPF级、雄性SD大鼠20只，安乐死后分离胸主动脉血管中膜，将获得的VSMC分为5组:空白对照组、ox-LDL组、ox-LDL＋LA（20、80、100&#8197;mg/L）组。空白对照组不加任何药物，各实验组以ox-LDL为泡沫细胞诱导剂，加入不同浓度的LA，分别测定VSMC内TG、TC、SOD和GSH-PX的活性。结果 ox-LDL组TG、TC、SOD和GSH-PX值与空白对照组比较差异有统计学意义（P<0.05）；LA各浓度干预组（20、80和100&#8197;mg/L）TG、TC、SOD和GSH-PX值与ox-LDL组比较差异有统计学意义（P<0.05）,各LA剂量组之间比较差异有统计学意义（P<0.05）。结论 LA可抑制ox-LDL诱导VSMC的脂质堆积，抑制泡沫细胞的形成，这可能与其抗氧化活性有关。     

β-七叶皂甙钠对大鼠脑缺血-再灌注损伤炎症反应的影响

目的探讨β-七叶皂甙钠对脑缺血-再灌注损伤的保护作用。方法45只Wistar大鼠随机平均分为假手术组、生理盐水对照组和β-七叶皂甙钠治疗组。线栓法阻塞大鼠右侧大脑中动脉,制备局灶性脑缺血-再灌注模型,在脑缺血2h、再灌注24h后,分别对各组大鼠的神经行为学变化评分,对缺血区白介素1β（IL-1β）和肿瘤坏死因子（TNF-α）进行测定和分析。结果在脑缺血2h再灌注24h后治疗组与对照组相比,前者行为学评分优于后者（P〈0.05）,IL-1β和TNF-α含量降低（P〈0.05）。结论炎症反应参与了脑缺血-再灌注损伤,β-七叶皂甙钠可以降低缺血-再灌注后脑组织中的IL-1β和TNF-α含量,减轻梗死体积,减轻炎症反应,对局灶性脑缺血-再灌注损伤可能具有一定的保护作用。     

Effect of mild hypothermia on focal cerebral ischemia. Review of experimental studies

The purposes of this review are to clarify the effect of hypothermia therapy on focal cerebral ischemia in rats, and to consider the relevancy of its application to human focal cerebral ischemia. Since 1990, 26 reports confirming the brain-protecting effect of hypothermia in rat focal cerebral ischemia models have been published. Seventy-four experimental groups in these 26 reports were classified as having transient middle cerebral arterial occlusion (MCAO) with mild hypothermia (group A; 43 groups), permanent MCAO with mild hypothermia (group B; 14 groups), permanent MCAO with deep hypothermia (group C; 8 groups) and transient or permanent MCAO with mild hyperthermia (group D; 9 groups). The results were evaluated as the % infarct volume change caused by hypothermia or hyperthermia compared with the infarct volume in normothermic animals. The effectiveness was confirmed in 36 (83%) of the 43 groups in group A, 10 (71%) of the 14 in group B, and six (75%) of the eight in group C. The infarct volume of eight of the nine groups in group D was markedly aggravated. The percent infarct volume change was 55.3% +/- 27.1% in group A, 57.6% +/- 24.7% in group B, 60.8% +/- 45.5% in group C, and 189.7% +/- 89.4% in group D. For effective reduction of the infarct volume, hypothermia should be started during ischemia or within 1 h, at latest, after the beginning of reperfusion in the rat transient MCAO model. However, it is not clear whether this neuroprotective effect of hypothermia can also be observed in the chronic stage, such as several months later. Keeping the body temperature normothermic in order to avoid mild hyperthermia seems to be rather important for not aggravating cerebral infarction. Clinical randomized studies on the efficacy of mild hypothermia for focal cerebral ischemia and sophisticated mild hypothermia therapy techniques are mandatory.     

Effects of mild (33°C) and moderate (29°C). hypothermia on cerebral blood flow and metabolism,lactate, and extracellular glutamate in experimental head injury

Abstract

The effects of mild (33±C) and moderate (29±C) hypothermia were investigated to determine which temperature was more effective against compression-induced cerebral ischemia. Eighteen cats were anesthetized. The animals were divided into three groups according to deep-brain temperature (control, 37±C; mild hypothermia,33±C; and moderate hypothermia,29±C). Intracranial pressure (ICP) and cerebral blood flow (CBF) were monitored, the latter by hydrogen clearance. Arteriovenous oxygen difference (AVD02) and cerebral venous oxygen saturation (SCV02) were measured in blood samples from the superior sagittal sinus. The cerebral metabolic rate of oxygen (CMR02) and the cerebral metabolic rate of lactate (CMR lactate) were calculated. Extracellular glutamate was measured by microdia lysis. ICP was increased by inflation of an epidural balloon until CBF became zero, and this ischemia was maintained for 5 mint after which the balloon was quickly deflated. All parameters were recorded over 6 h. Evans blue was injected to examine vascular permeability changes. CBF was decreased by 56% by mild hypothermia and by 77% by moderate hypothermia. Mild hypothermia had a coupled metabolic suppression whereas moderate hypothermia significantly increased AVD02 and decreased SCV02, producing a low CBF, CMR02 (relative ischemia). After bc;lIoon deflation, all three groups showed reactive hyperemia, which was significantly reduced by mild and moderate hypothermia. CBF then decreased to 50% of pre-inflation values and SCVO₂ decreased (post-ischemic hypoperfusion). CBF,CMRO2, SCV02, and AVD0₂ did not differ significantly between the three groups. After balloon deflation, all three groups showed increased CMR lactate, which was significantly reduced by mild and moderate hypothermia. Extracellular glutamate increased in control animals (3.8 ± 1-72 μM), an effect most effectively suppressed in the mild hypothermia group (1.0± 0.46 pM). Damaged tissue volumes as indicated by Evans blue dye extravasation were 729± 89 mm3 in control, 247± 56 mm³ in mild hypothermia, and 267± 35 mm³ in moderate hypothermia animals. These data suggest that mild hypothermia (33±C) might be the optimal brain temperature to treat compression-related cerebral ischemia. [Neural Res 1998; 20: 719-726]     

亚低温对大鼠脑缺血再灌注损伤后热休克蛋白70及胶质纤维酸性蛋白表达的影响

目的观察亚低温对大鼠脑缺血再灌注损伤后热休克蛋白70(HSP70)及胶质纤维酸性蛋白(GFAP)表达的影响。方法将雄性Wistar大鼠30只分为假手术组、常温组和亚低温组。制作右侧大脑中动脉阻塞(MCAO)模型,观察缺血2h再灌注48h后各组大鼠脑组织学改变和HSP70及GFAP的表达。结果常温组大鼠脑皮质下神经元严重坏死,亚低温组皮质下神经元坏死严重程度明显较常温组轻,假手术组未见神经元坏死。常温组大鼠脑组织GFAP和HSP70阳性细胞较多,假手术组、亚低温组GFAP和HSP70阳性细胞少于常温组,假手术组偶见HSP70阳性细胞;图像分析显示,常温组大鼠脑组织GFAP、HSP70表达的平均光密度较假手术组和亚低温组明显增高(均P<0.01)。结论亚低温能减轻大鼠脑缺血再灌注损伤,降低脑组织HSP70及GFAP蛋白的表达。     

不同低温对鼠永久性大脑中动脉阻塞后NF-κB表达及脑梗死体积的影响

目的:观察不同低温对大鼠永久性大脑中动脉阻塞后NF-κB表达及梗死体积的影响。方法:120只雄性SD大鼠随机分为三组:常温组(37℃),轻度低温组(34℃),中度低温组(32℃),每组分缺血2,4,6,12小时共四个亚组。采用栓线法制作永久性大脑中动脉阻塞(MCAO)模型,各组大鼠分别于缺血2,4,6,12小时后置于常温操作台和冰毯机上,分别保持肛温为37±0．5℃,34±0．5℃和32±0．5℃12小时。在各自规定时间点处死大鼠,其中三只作TTC染色,剩余作免疫组织化学染色。结果:与常温组相比,在缺血的各个时间点,除轻度低温组缺血6h外,两低温组的脑梗死体积均显著减小(P<0．05或P<0．01)。随缺血时间的延续,常温组NF-κB蛋白表达逐渐升高,在缺血6小时达高峰,并持续升高:除轻度低温组缺血4h外,在其余各时间点,两低温组的NF-κB蛋白水平较常温组显著下降(P<0．01),且低温治疗使NF-κB蛋白表达高峰前移。结论:低温治疗组与常温组比较,脑梗死体积显著减小(P<0．05或P<0．01);低温治疗还显著抑制NF-κB的蛋白表达(P<0．01),使NF-κB蛋白表达高峰前移。低温的脑保护作用可能与抑制NF-κB的表达有关。     

亚低温治疗大鼠缺血性脑水肿研究

目的研究亚低温对延迟时间窗再灌注的局灶脑缺血大鼠缺血性脑水肿的治疗作用。方法 SD雄性大鼠96只,线栓法制作大脑中动脉闭塞模型后随机分为缺血3 h组、缺血6 h组、缺血9 h组(每组各30只),分别在造模3 h、6 h和9 h后拔出线栓,使大脑中动脉再灌注。各缺血组按照再灌注后是否给予亚低温治疗及亚低温持续时间分为常温、亚低温3 h和亚低温5 h三个亚组,每个亚组有10只大鼠。另设假手术组6只。缺血组大鼠在再灌注24 h后处死取脑,假手术组在术后24 h处死取脑,干-湿重法测定各组缺血侧脑组织含水量并进行比较。结果与假手术组比较,缺血组缺血侧脑组织含水量明显增高。缺血3 h组中3 h亚低温和5 h亚低温亚组的缺血侧脑组织含水量与缺血3 h常温组比较,差异有统计学意义(79.39%±2.44%vs82.16%±1.50%,P0.05;79.20%±1.55%vs 82.16%±1.50%,P0.05)。其余各缺血组中经过亚低温治疗的大鼠与常温亚组的脑组织含水量无统计学差异。结论亚低温可减轻缺血早期(3 h)再灌注的脑组织水肿,保护缺血脑组织,而对晚期(6 h和9 h)再灌注的缺血性脑水肿无论亚低温时间长短均无明显保护作用。     

病变侧亚低温对大鼠局脑缺血再灌注后Akt、Survivin表达的影响

目的 通过检测Akt及Survivin蛋白的表达,探讨亚低温对局脑缺血再灌注后神经元存活的影响.方法 用线拴法制作大鼠大脑中动脉闭塞（MCAO）局脑缺血再灌注模型,将44只SD大鼠随机分成假手术组、常温缺血组和亚低温缺血组,缺血组分别缺血2,6 h再灌注4,24,72 h,1周,2周后处死,亚低温组于缺血后13～14 min实施病灶侧亚低温持续4 h.免疫组织化学法检测Akt、Survivin 蛋白的表达.结果 相同缺血再灌注时间点,亚低温组比常温组缺血侧Akt、Survivin、表达水平显著增高（P＜0.05）.结论 病灶侧亚低温通过促进缺血半暗带脑组织Akt、Survivin表达的核内移,从而抑制神经元凋亡,促进脑缺血后神经功能恢复.     

Mild hypothermia effects on intercellular adhesion molecule-1 and serum interleukin-6 expression in brain tissues of a rat focal ischemia model

BACKGROUND： Previous studies have confirmed the neuroprotective effect of mild hypothermia on ischemic brain injury. OBJECTIVE： To investigate the effects of mild hypothermia on intercellular adhesion molecule-1 expression and serum interleukin-6 levels in ischemic brain tissues of focal brain ischemia rats, and to explore the neuroprotective effects of mild hypothermia on ischemic brain injury. DESIGN, TIME AND SETTING： A randomized, controlled, neurobiological experiment was performed at the Central Laboratory, First Affiliated Hospital, Xinxiang Medical College, China from February to July 2006. MATERIALS： Thirty healthy, adult, Sprague Dawley rats were used to establish middle cerebral artery occlusion models using the suture method, The immunohistochemistry （streptavidin-biotin-peroxidase complex method） kit was purchased from Boster, China. Interleukin-6 radioimmunoassay was supplied by Institute of Radioimmunity, Technology Development Center, General Hospital of Chinese PLA. METHODS： The rats were equally and randomly assigned into mild hypothermia and control groups, and middle cerebral artery occlusion models were established. The rectal temperature was maintained at （37 ±0.5）℃ in the control group. In the mild hypothermia group, the rectal temperature was maintained at （33±1）℃. MAIN OUTCOME MEASURES： At 12 hours after model establishment, the ischemic brain hemispheres were coronally sliced at the level of the optic chiasm. The number of intercellular adhesion molecule-1-positive vessels per high-power field was observed with an optical microscope. Serum interleukin-6 levels were measured by radioimmunoassay. RESULTS： Compared with the control group, intercellular adhesion molecule-1 and serum interleukin-6 expressions were significantly decreased in ischemic brain tissues of the mild hypothermia group （P 〈 0.01）. CONCLUSION： Mild hypothermia exhibits a neuroprotective effect by reducing serum interleukin-6 and intercellular adhesion molecule-1 expression followi     

Therapeutic effect of post-ischemic hypothermia duration on cerebral ischemic injury

OBJECTIVE: To study the efficacy of post-ischemic mild brain hypothermia lasting for different time intervals on cerebral ischemic reperfusion injury. METHOD: Male Sprague-Dawley rats were divided into a sham-operated group, normothermia (37-38 degrees C) ischemia group and mild hypothermia (31-32 degrees C) group. The last group was subdivided into four groups: 30 minute hypothermia plus 210 minute normothermia, 60 minute hypothermia plus 180 minute nomothermia,120 minute hypothermia plus 120 minute normothermia, and 240 minute hypothermia (n=8). Global cerebral ischemia was established using the Pulsinelli four-vessel occlusion model. Brain tissue was collected following a 20 minute cerebral ischemia and 240 minute reperfusion, and was used to measure the levels of glutamate (Glu), aspartate (Asp), glycine (Gly), gamma-aminobutyric acid (GABA), dopamine (DA), norepinephrine (NE), serotonin(5-HT) and hydroxyindoleacetic acid (5-HIAA), nitrite (NO(2)), endothelin-1 (ET(1)), tumor necrosis factor alpha(TNFalpha) and interleukin-1beta (IL-1beta). Serum was collected to measure the levels of lactate dehydrogenase (LDH), aspartate aminotransferase (AST), creatine kinase (CK) and its brain band isoenzyme (CK-BB). RESULTS: Hypothermia lasting for 60-240 minutes delayed the decrease in these amino acids, postponed the decrease in DA, NE and 5-HT and increase in hydroxyindoleacetic acid (5-HIAA), and decreased the levels of IL-1beta, TNFalpha, ET(1) and NO(2) in brain tissue. Hypothermia also decreased the levels of LDH, AST, CK and CK-BB in serum as compared to normothermia group (p<0.05 or p<0.01). Hypothermia lasting for 30 minutes delayed the decreases in these amino acids and 5-HT and increase in 5-HIAA in brain tissue (p<0.05), but failed to influence the levels of IL-1beta, TNFalpha, ET(1) and NO(2) in brain tissue and the amounts of LDH, AST, CK and CK-BB in serum as compared to normothermia ischemia group (p>0.05). CONCLUSIONS: Post-ischemic mild brain hypothermia can significantly suppress the excessive release of amino acids, monoamine neurotransmitters and inflammation response in ischemic tissue. It can also stabilize the function of the cell membrane, which is associated with the mechanism of cerebral protection by mild hypothermia. These results suggest that mild hypothermia should be applied immediately after ischemia and last for more than 60 minutes in order to obtain neuroprotective effects.     

桂皮醛对脑缺血小鼠的脑保护作用及对Toll样受体6/核因子-κB信号通路的影响

目的探讨桂皮醛对局灶性脑缺血小鼠的脑保护作用及机制。方法雄性CD-1小鼠通过腹腔注射的方法给予桂皮醛干预,应用改良线栓法建立小鼠右侧永久性大脑中动脉闭塞模型,将成年健康雄性CD-1小鼠随机分为大脑中动脉闭塞(MCAO)组及桂皮醛(CA)低、中、高剂量干预组,即CA25组、CA50组和CA75组(在MCAO小鼠模型基础上腹腔给予25 mg/kg、50 mg/kg及75 mg/kg桂皮醛)。术后24 h通过测定小鼠神经功能缺损评分、脑梗死体积及脑组织含水量来评价桂皮醛的脑保护作用。通过Western blot法和实时荧光定量PCR法测定Toll样受体6(TLR6)、肿瘤坏死因子受体相关分子6(TRAF6)和核因子-κB(NF-κB)在脑组织中的表达。结果与MCAO组相比,CA50组神经功能评分显著改善(中位数2.0 vs.3.5),病变侧脑组织含水量降低[(83.72±0.73)%vs.(85.09±0.95)%],脑梗死体积缩小(0.45±0.06 vs.0.54±0.02),均P0.05。同样与MCAO组相比,CA50组TLR6、TRAF6及NF-κB基因表达明显下调(TLR6:3.26±0.03 vs.6.32±0.07;TRAF6:1.88±0.21 vs.3.33±0.48;NF-κB:1.47±0.33 vs 4.21±0.57,均P0.05)。TLR6、TRAF6及胞核NF-κB蛋白表达明显下降(TLR6:0.12±0.01 vs.0.19±0.03;TRAF6:0.45±0.09 vs.0.67±0.07;胞核NF-κB:0.32±0.06 vs.0.46±0.06,均P0.05)。结论桂皮醛可能通过抑制TLR6/TRAF6/NF-κB通路对局灶性脑缺血小鼠发挥脑保护作用。