自噬在大鼠蛛网膜下腔出血后早期脑损伤中作用的实验研究

目的探讨大鼠蛛网膜下腔出血(SAH)模型中,应用激动剂rapamycin(RAP)增强自噬后观察SAH后早期大鼠神经功能评分、脑水肿和血-脑屏障(BBB)通透性的变化,以及应用抑制剂3-Methyladenine(3-MA)减弱自噬后上述指标的变化。探讨自噬在SAH后早期脑损伤(EBI)中可能的作用。方法雄性SD大鼠60只,随机分为对照组、SAH组、SAH+vehicle组、SAH+RAP组和SAH+3-MA组5组,每组12只,于24 h时间点处死动物后取颞底脑皮层,利用western blot法测定自噬标志物LC3和Beclin-1的表达变化,分别观察各组大鼠神经功能评分的变化,并测定各组大鼠脑水肿和BBB通透性的变化。结果 SAH后脑皮层中LC3和Beclin-1表达较对照组明显增加(均P0.01),同时伴有明显的脑水肿(P0.01)及BBB通透性破坏(P0.01);与SAH+vehicle组相比SAH+RAP组LC3和Beclin-1的表达明显增加(均P0.05),脑水肿指数下降(P0.01),BBB通透性好转(P0.01),同时大鼠的神经功能评分明显好转(P0.01)。而SAH+3-MA组与SAH+vehicle组相比,LC3和Beclin-1的表达明显下降(均P0.01),大鼠神经功能评分变差(P0.05)。结论应用RAP干预自噬后,LC3和Beclin-1的表达明显增高,自噬明显增强,同时大鼠神经功能评分明显好转,脑水肿指数明显下降,BBB通透性明显好转。自噬增强后能减轻SAH后的EBI;3-MA的应用可使EBI加重。     

p38丝裂原活化蛋白激酶途径对大鼠脑缺血再灌注后脑组织基质金属蛋白酶-9表达及脑水肿形成的影响

目的探讨p38丝裂原活化蛋白激酶(MAPK)途径对大鼠脑缺血再灌注后脑组织基质金属蛋白酶-9(MMP-9)表达及脑水肿形成的影响。方法 54只SPF级雄性SD大鼠,随机分为假手术组(Sham组)、缺血再灌注组(I/R组)和p38抑制剂组(SB组)。采用改良线栓法制备大鼠大脑中动脉缺血再灌注模型。再灌注24 h后对大鼠进行神经功能缺损评分,Evans Blue法测定血-脑屏障通透性;干湿比重法测定脑组织含水量,采用Western blot检测缺血周边区脑组织磷酸化p38(p-p38)和MMP-9的表达。结果与Sham组相比,I/R组大鼠神经功能缺损加重(P0.05);与I/R组相比,SB组大鼠神经功能缺损明显减轻(P0.05)。与Sham组比较,I/R组血-脑屏障通透性及脑含水量明显增加(均P0.05);与I/R组相比,SB组血-脑屏障通透性及脑含水量降低(均P0.05)。与Sham组相比,I/R组大鼠缺血周边区脑组织p-p38、MMP-9的表达明显上调(均P0.05);与I/R组相比,SB组大鼠缺血周边区脑组织p-p38、MMP-9的表达明显下调(均P0.05)。结论 p38 MAPK参与了大鼠脑缺血再灌注后脑水肿的形成,机制可能为大鼠脑缺血再灌注后激活p38MAPK使缺血周边区脑组织MMP-9的表达上调,破坏血-脑屏障通透性,导致脑水肿发生。     

蛛网膜下腔出血后大鼠基底动脉p38MAPK信号传导途径研究

目的探讨蛛网膜下腔出血(SAH)后大鼠基底动脉中p38丝裂原活化蛋白激酶(p38MAPK)信号传导通路的活化情况以及与脑血管痉挛(CVS)的关系。方法通过枕大池二次注血方法制作大鼠SAH模型,以免疫组化方法和逆转录酶-多聚酶链反应分析,分别从蛋白、基因水平分析SAH后基底动脉中p38MAPK信号传导通路的活化情况。结果 SAH后大鼠基底动脉逐渐出现痉挛。基底动脉磷酸化p38MAPK表达逐渐增加,3 d时达高峰并持续至第5 d,14 d时恢复正常。p38MAPK基因表达在注血后1 d明显增加,逐渐增加,于5 d时达高峰,14 d仍维持较高水平。结论SAH后大鼠基底动脉中p38MAPK信号传导通路激活,可能诱导CVS的发生。     

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.     

银杏内酯、银杏黄酮对脑淋巴阻滞后SAH大鼠脑组织HO-1表达的影响

目的 探讨银杏内酯、银杏黄酮对脑淋巴引流阻滞(CLB)后蛛网膜下腔出血(SAH)大鼠脑组织血红素氧合酶-1(HO-1)表达的影响.方法 将48只Wistar大鼠分为正常对照组、SAH组、SAH+CLB组、SAH+CLB+生理盐水(NS)组、SAH+CLB+银杏内酯干预组(又分为低剂量、高剂量组)、SAH+CLB+银杏黄酮干预组(又分为低剂量、高剂量组).用结扎颈部淋巴管、摘除淋巴结及注入自体动脉血法制作CLB和SAH大鼠模型.制作CLB模型后24h诱导SAH模型.用RT-PCR法检测大鼠脑组织HO-1mRNA的表达.结果 各模型组大鼠脑组织HO-1mRNA表达明显高于正常对照组(均P＜0.01),其中以SAH+CLB组、NS组表达进一步增强.银杏内酯和银杏黄酮组HO-1mRNA的表达水平明显高于SAH+CLB组、NS组(均P＜0.01),其中两高剂量组表达又明显高于低剂量组(均P＜0.01),两低剂量组大鼠脑组织HO-1mRNA的表达与SAH+CLB组及NS组差异无统计学意义(P＞0.05).结论 CLB可诱导SAH鼠脑组织HO-1表达水平明显增高,银杏内酯和银杏黄酮对之有促进作用,尤以高剂量组效果更明显.     

基于NF-κB/ICAM-1信号通路探究miR-223-3p对大鼠蛛网膜下腔出血早期脑损伤的影响

目的 阐明微小核糖核酸(Micro RNA,miR)-223-3p在蛛网膜下腔出血(Subarachnoid hemorrhage, SAH)后影响早期脑损伤(Early brain injury, EBI)中的作用及其潜在机制。方法 建立SAH大鼠模型，评估神经行为学功能、血脑屏障通透性、脑含水量、神经元凋亡和炎症因子水平；氧合血红蛋白诱导SAH细胞模型；测定细胞凋亡率、乳酸脱氢酶、活性氧水平；检测miR-452-3p在SAH大鼠模型和氧血红蛋白诱导SAH细胞模型中的表达水平；检测核因子κB(Nuclear factor kappa-B,NF-κB)/细胞间黏附分子-1(Intercellular cell adhesion molecule-1,ICAM-1)信号通路相关蛋白的表达水平。结果 SAH大鼠中miR-223-3p表达水平上调，降低神经功能评分，增加血脑屏障通透性、脑含水量和神经元凋亡，促炎因子表达水平升高，并降低抗炎因子水平，NF-κB/ICAM-1信号通路被激活；SAH增加了氧血红蛋白处理的神经元凋亡率、乳酸脱氢酶释放和活性氧水平；miR-223-3p的抑制逆转了上述...     

辛伐他汀对蛛网膜下腔出血早期脑损伤大鼠NLRP3炎性小体的表达及NF-κB信号通路的影响

目的 探究辛伐他汀(simvastatin)对蛛网膜下腔出血(SAH)早期脑损伤(EBI)大鼠NLRP3的表达及NF-κB信号通路的影响。方法 100只大鼠随机分为假手术(Sham)组、SAH组、Simvastatin组、NF-κB信号通路抑制剂(PJ34)组,每组25只。视交叉前池注血法构建SAH模型,建模后2h给药,Simvastatin组、PJ34组腹腔注射辛伐他汀和PJ34,另外两组腹腔注射等体积生理盐水。1次·d^-1,连续14 d。给药结束24 h后,采用Garcia评分评估造模后大鼠的神经功能;Sugawara出血量评分评价脑组织出血情况;苏木精-伊红染色、透射电镜观察脑组织病理变化与超微结构损伤;测定脑组织含水量;TUNEL染色、ELISA、免疫组化分别检测细胞凋亡情况、炎症因子表达水平与NLRP3表达情况;Western blotting检测脑组织NLRP3、Caspase-1、核因子-κB (NF-κB-p65)的表达水平。结果 与SAH组相比,Simvastatin组SAH、炎性浸润明显减轻,脑组织病理损伤明显改善,脑组织含水量、神经细胞凋亡、...     

水通道蛋白4对一氧化碳中毒后迟发性脑病大鼠神经损伤的影响

目的 探讨水通道蛋白4(Aquaporin 4,AQP4)对一氧化碳(Carbon monoxide,CO)中毒后迟发性脑病(Delayed encephalopathy,DEACMP)大鼠神经损伤的影响。方法 将210只雄性SD大鼠随机分为空白对照(Blank control,BC)组、CO中毒(CO)组、钠-钾-氯共转运体(Na⁺-K⁺-Cl^- cotransporter,NKCC)抑制剂处理(布美他尼)组、p38-丝裂原活化蛋白激酶(Mitogen activated protein kinase,MAPK)抑制剂处理(MAPK)组和AQP4特异性抑制剂处理(AQP4抑制剂)组,每组各42只; 根据造模后不同时间点将每组大鼠进一步分为染毒3、6、12、24、48、72 h和7 d后共7个亚组,每亚组各6只; 取大鼠脑前额叶皮质组织,计算脑皮质含水量,采用HE法观察脑皮质形态; 采用免疫组化链霉菌抗生物素蛋白-过氧化物酶(Streptavidin-perosidase,SP)染色法测定大鼠脑皮质AQP4,p38 MAPK,NKCC1、胶质纤维酸性蛋白(Glial fibrillary acidic protein,GFAP)和S100钙结合蛋白B(S100 calcium binding protein B,S100B)蛋白表达水平。结果 与BC组比较,CO组大鼠在染毒3、6、12、24、48、72 h后尾静脉COHB水平和脑皮质含水量显著升高,脑皮质AQP4,p38 MAPK,NKCC1,GFAP和S100B蛋白表达水平显著升高,染毒7 d后恢复正常(P<0.05); 与CO组比较,布美他尼组、MAPK组和AQP4抑制剂组大鼠脑皮质含水量显著降低,脑皮质AQP4,p38 MAPK,NKCC1,GFAP和S100B蛋白表达水平显著降低,且AQP4抑制剂组变化更明显(P<0.05)。结论 p38-MAPK/NKCC信号通路可能参与调控CO中毒DEACMP大鼠脑皮质AQP4表达,抑制AQP4表达可有效减轻大鼠脑水肿并改善预后,有望成为预防和治疗DEACMP的新靶点。     

黄体酮减轻大鼠蛛网膜下腔出血后早期脑损伤

目的 探讨黄体酮对蛛网膜下腔出血(SAH)后早期脑损伤(EBI)中细胞凋亡、血脑屏障(BBB)稳定性、脑水肿和死亡率方面的保护作用.方法 66只大鼠被随机分为假手术组、SAH+溶剂组、SAH+黄体酮组.于SAH模型制成后1h、6h和12h分别给予黄体酮(16毫克/千克体重)或等体积的溶剂.在SAH后24h分析不同组间大鼠在死亡率、神经功能评分、脑水肿、细胞凋亡、caspase-3及基质金属蛋白酶-9(MMP-9)表达水平的差异.结果 与SAH+溶剂组比较,黄体酮治疗显著降低了大鼠的死亡率、细胞凋亡程度以及caspase-3水平与MMP-9的表达水平,减轻了脑水肿和伊文思蓝的渗出,提高了神经功能评分.结论 黄体酮可通过抑制细胞凋亡和稳定BBB减轻SAH后EBI.     

蛛网膜下腔出血后早期海马ADAMTS-1的表达与血脑屏障通透性的相关性研究

目的研究大鼠蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后早期海马组织中ADAMTS-l(a disintegrin-like and metalloproteinase with thrombospondin type l motifs)表达情况及其与血脑屏障通透性的关系,初步探讨ADAMTS-l在实验性大鼠SAH后早期脑损伤(early brain injury,EBI)中的作用。方法成年雄性SD大鼠108只,分假手术组和SAH组。采用大鼠视交叉前池注血模型,于SAH后6、12、24、48、72 h时间点,应用Western-Blotting和RT-PCR法检测大鼠海马ADAMTS-1蛋白及mRNA表达变化,同时应用甲酰胺浸泡法检测大鼠脑内伊文氏蓝(Evans blue,EB)含量。结果大鼠SAH后6 h、12 h组海马ADAMTS-1mRNA及蛋白表达与sham组相比无统计学意义,于出血后24 h表达明显升高,48 h达到高峰,72 h后仍维持在较高水平。脑内伊文氏蓝含量亦于出血后24 h明显升高,48 h达到高峰并于72 h仍维持在较高水平。ADAMTS-1蛋白表达与脑内EB含量成正相关(r=0.936,P=0.014)。结论大鼠SAH后早期脑损伤过程中ADAMTS-l的表达与血脑屏障损伤成正相关,提示ADAMTS-l可能参与SAH后早期脑损伤的病理过程。     

虾青素对小鼠蛛网膜下腔出血早期脑损伤的保护机制的研究

目的 研究虾青素对小鼠蛛网膜下腔出血（SAH）早期脑损伤的保护机制。方法 ICR雄性小鼠采用随机数字法随机分为四组：蛛网膜下腔出血组、假手术组、蛛网膜下腔出血+溶剂组（DMSO）、蛛网膜下腔出血+虾青素组。通过建立小鼠视交叉注血方法建立蛛网膜下腔出血模型，于手术后24 h记录神经功能评分，并应用末端脱氧核苷酸转移酶介导的生物素脱氧尿嘧啶核苷酸缺口末端标记法（TUNEL）、western blot法检测脑组织中的NOX2蛋白含量、ELISA法检测TNF-a/IL-1β水平，干湿法检测脑组织中含水量。结果 与对照组相比，SAH后小鼠神经功能损伤评分加重，脑水肿加重，脑组织中的NOX2蛋白及脑组织中凋亡阳性细胞数也显著增多，TNF-a/IL-1β值明显升高；应用虾青素干预以后，小鼠神经功能改善，脑组织凋亡阳性细胞明显减少。同时，虾青素能够降低SAH后小鼠脑组织中NOX2蛋白，TNF-a/IL-1β水平值也明显降低。结论 虾青素对sAH后早期脑损伤（EBI）具有保护作用，其作用机制可能与其抗氧化性有关。     

C3G通过PKA/CREB信号通路减轻成年小鼠SAH后早期脑损伤

目的 探讨矢车菊素-3-O-葡萄糖苷(C3G)对小鼠蛛网膜下腔出血(SAH)后早期脑损伤(EBI)的影响及作用机制。方法 取72只雄性C57小鼠随机分成6组:假手术组、SAH组、溶剂组、低剂量C3G组(10 mg/kg)、中剂量C3G组((20 mg/kg)、高剂量C3G组(30 mg/kg);每组12只。应用颈动脉穿刺法制作小鼠SAH模型,术后24 h进行Garcia评分和平衡木评分评估神经功能;每组小鼠随机取6只取外周血检测活性氧(ROS)和丙二醛(MDA)含量,然后取出完整脑组织进行SAH出血评分、脑水含量检测;每组剩余6只小鼠取外周血检测GSH/GSSG水平,然后取脑组织应用免疫印迹法检测PKA、p-PKA、CREB、p-CREB和GCLC表达水平。结果 与假手术组相比,SAH组小鼠神经功能评分明显下降(P<0.05),脑水含量、SAH出血评分、外周血ROS和MDA含量均显著增加(P<0.05),外周血GSH/GSSG比值明显下降(P<0.05),脑组织p-PKA、p-CREB和GCLC表达明显上调(P<0.05)。C3G明显增加小鼠神经功评分(P<...     

Neuritin attenuates early brain injury in rats after experimental subarachnoid hemorrhage

Objectives: Early brain injury (EBI) is central to the pathological progress of subarachnoid hemorrhage (SAH). In this study, we determined if neuritin protects the brain against EBI in rats and discussed the role of apoptosis pathway mediated by endoplasmic reticulum stress in this neuroprotective route. Methods: A total of 96 male Sprague Dawley rats were divided into control, sham, SAH and SAH + neuritin groups. The rat SAH model was induced by injection 0.3 mL of nonheparinized arterial blood into the prechiasmatic cistern. Mortality assay, neurological scores, brain water content measurement, Evans blue dye assay, TUNEL stain assay and Western blot analysis were performed. Results: Neuritin significantly improved the neurological scores, brain water content, blood-brain barrier (BBB) and apoptosis compared with the control and sham groups within 24 h after SAH. TUNEL staining assay results demonstrated that apoptosis was ameliorated, MMP-9 expression was reduced, whereas GRP78, CHOP, caspase-12 and ASK1 levels were markedly preserved after neuritin application. Conclusions: Our study demonstrated that neuritin plays a neuroprotective role on EBI after SAH by attenuating BBB disruption, brain edema and apoptosis.     

Role of P38 mitogen-activated protein kinase on Cx43 phosphorylation in cerebral vasospasm after subarachnoid hemorrhage

Objectives: Cx43 phosphorylation is involved in the pathogenesis of cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH). However, the exact phosphorylation mechanism of Cx43 in CVS is not fully elucidated. Thus, we examined the role of P38MAPK in CVS and Cx43 phosphorylation, using a double hemorrhage rat model.

Methods: Sprague–Dawley rats weighing 300–350?g were grouped into sham, SAH, vehicle, and SAH?+?SB203580. SAH was induced by double injecting blood into the prechiasmatic cisterns. Neurological score was measured with the Garcia scoring system, and the diameters of basilar arteries and the expression of pCx43, pP38MAPK, and P38MAPK proteins were measured through pressure myograph measurement and Western blot analysis, respectively.

Results: The neurological scores remarkably decreased after SAH but remarkably improved after SB203580 was used. The results of pressure myograph analysis on the SAH and vehicle groups showed the considerable narrowing of the basilar arteries in comparison with that of the sham group. By contrast, the arterial diameters in the SAH?+?SB203580 group were much larger than those observed in the SAH and vehicle groups. Moreover, the P38MAPK expression in the sham group had no substantial change in contrast to the SAH and vehicle groups, and pCx43 and pP38MAPK increased in the SAH and vehicle groups. Meanwhile, the SAH?+?SB203580 group showed marked decrease in Cx43 and P38MAPK phosphorylation levels relative to the SAH and vehicle groups.

Conclusions: P38MAPK pathway facilitates the development of CVS through the upregulation of Cx43 phosphorylation.     

黄体酮对蛛网膜下腔出血后皮层TLR4/NF-κB传导通路的影响

目的 探讨黄体酮对蛛网膜下腔出血(SAH)所致的早期脑损伤(EBI)后大脑皮层Toll 样受体4(TLR4)/核因子-κB(NF-κB)传导通路的调控作用.方法 雄性SD 大鼠32 只,随机分为对照组、蛛血组、安慰剂组及黄体酮组,取大鼠尾动脉非肝素化动脉血注入视交叉前池致蛛网膜下腔出血模型,黄体酮注射剂量为16 mg/...     

Fluoxetine is Neuroprotective in Early Brain Injury via its Antiinflammatory and Anti-apoptotic Effects in a Rat Experimental Subarachnoid Hemorrhage Model

Fluoxetine, an anti-depressant drug, has recently been shown to provide neuroprotection in central nervous system injury, but its roles in subarachnoid hemorrhage(SAH) remain unclear. In this study, we aimed to evaluate whether fluoxetine attenuates early brain injury(EBI) after SAH. We demonstrated that intraperitoneal injection of fluoxetine(10 mg/kg per day) significantly attenuated brain edema and blood-brain barrier(BBB) disruption, microglial activation, and neuronal apoptosis in EBI after experimental SAH, as evidenced by the reduction of brain water content and Evans blue dye extravasation, prevention of disruption of the tight junction proteins zonula occludens-1, claudin-5, and occludin, a decrease of cells staining positive for Iba-1, ED-1, and TUNEL and a decline in IL-1 b, IL-6, TNF-a, MDA, 3-nitrotyrosine, and 8-OHDG levels. Moreover, fluoxetine significantly improved the neurological deficits of EBI and long-term sensorimotor behavioral deficits following SAH in a rat model. These results indicated that fluoxetine has a neuroprotective effect after experimental SAH.     

Propofol Reduces Inflammatory Brain Injury after Subarachnoid Hemorrhage: Involvement of PI3K/Akt Pathway

Background: Our previous study showed that propofol, one of the widely used anesthetic agents, can attenuate subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) via inhibiting inflammatory and oxidative reaction. However, it is perplexing whether propofol attenuates inflammatory and oxidative reaction through modulating PI3K/Akt pathway. The present study investigated whether PI3K/Akt pathway is involved in propofol's anti-inflammation, antioxidation, and neuroprotection against SAH-induced EBI. Materials and methods: Adult Sprague-Dawley rats underwent SAH and received treatment with propofol or vehicle after 2 and 12 hours of SAH. LY294002 was injected intracerebroventricularly to selectively inhibit PI3K/Akt signaling. Mortality, SAH grading, neurological scores, brain water content, evans blue extravasation, myeloperoxidase, malondialdehyde, superoxide dismutase, and glutathione peroxidase were measured 24 hours after SAH. Immunoreactivity of p-Akt, t-Akt, nuclear factor- kappa B (NF-κB) p65, nuclear factor erythroid-related factor 2 (Nrf2), NAD(P)H:quinone oxidoreductase (NQO1), and cyclooxygenase-2 (COX-2) in rat brain was determined by western blot. Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in rat brain were examined by ELISA. Results: Propofol significantly reduces neurological dysfunction, BBB permeability, brain edema, inflammation, and oxidative stress, all of which were reversed by LY294002. Propofol significantly upregulates the immunoreactivity of p-Akt, Nrf2, and NQO1, all of which were abolished by LY294002. Propofol significantly downregulates the overexpression of NF-κB p65, COX-2, TNF-α, and IL-1β, all of which were inhibited by LY294002. Conclusion: These results suggest that propofol attenuates SAH-induced EBI by inhibiting inflammatory reaction and oxidative stress, which might be associated with the activation of PI3K/Akt signaling pathway.     

Fluoxetine is Neuroprotective in Early Brain Injury <Emphasis Type="Italic">via</Emphasis> its Anti-inflammatory and Anti-apoptotic Effects in a Rat Experimental Subarachnoid Hemorrhage Model

Fluoxetine, an anti-depressant drug, has recently been shown to provide neuroprotection in central nervous system injury, but its roles in subarachnoid hemorrhage (SAH) remain unclear. In this study, we aimed to evaluate whether fluoxetine attenuates early brain injury (EBI) after SAH. We demonstrated that intraperitoneal injection of fluoxetine (10 mg/kg per day) significantly attenuated brain edema and blood-brain barrier (BBB) disruption, microglial activation, and neuronal apoptosis in EBI after experimental SAH, as evidenced by the reduction of brain water content and Evans blue dye extravasation, prevention of disruption of the tight junction proteins zonula occludens-1, claudin-5, and occludin, a decrease of cells staining positive for Iba-1, ED-1, and TUNEL and a decline in IL-1β, IL-6, TNF-α, MDA, 3-nitrotyrosine, and 8-OHDG levels. Moreover, fluoxetine significantly improved the neurological deficits of EBI and long-term sensorimotor behavioral deficits following SAH in a rat model. These results indicated that fluoxetine has a neuroprotective effect after experimental SAH.     

白蛋白减轻大鼠液压颅脑损伤伤后脑水肿和神经功能障碍的剂量效应

目的 探讨白蛋白在治疗大鼠液压颅脑损伤后神经功能恢复和脑组织含水量的剂量效应。方法 将96只SD大鼠随机分为4组,液压打击致伤。伤后30min经尾静脉注射2g/kg(n=24,Ⅰ组)、1.2g/kg(n=24,Ⅱ组)、0.8g/kg(n=24,Ⅲ组)、0.4g/kg(n=24,Ⅳ组)20％人血白蛋白。每组取12只伤前、伤后当日、伤后连续7d进行行走、平衡和记忆实验,记录神经功能恢复情况。另每组12只伤后48h取双侧大脑半球测湿重、干重,计算脑组织含水量。结果 实验Ⅰ组动物的行走实验、平衡实验、记忆均优于其他组(P<0.01)。实验Ⅰ组的脑组织含水量为78.09±0.42％,Ⅱ组为79.01～0.66％,Ⅲ组为78.89±0.45％,Ⅳ组为79.03±0.35％,Ⅰ组脑水肿程度明显低于其它组(P<0.01)。结论 伤后早期使用大剂量白蛋白对大鼠液压颅脑损伤有明显促进神经功能恢复和减轻脑水肿的作用。