去铁敏对大鼠脑室出血后慢性脑积水与脑组织Wnt1、Wnt3a表达的影响

目的 观察去铁敏对大鼠脑室出血(IVH)后脑积水的干预效果及脑组织Wnt1、Wnt3a的表达影响.方法 雄性SD大鼠130只随机分为正常组、假性IVH组、IVH组及IVH加去铁敏组.采用脑室出血后慢性脑积水大鼠模型,于术后1 d、7 d及28 d处死大鼠,观察脑积水的发生率和脑组织中Wnt基因及蛋白表达情况.结果 正常组、假性IVH组未见脑积水发生,IVH组28 d脑积水发生率80%(12/15),显著高于IVH加去铁敏组28 d脑积水发生率20%(3/15).IVH后Wnt1、Wnt3amRNA及蛋白表达在7 d及28 d均显著高于假性IVH组,而去铁敏治疗组Wnt1、Wnt3a mRNA及蛋白表达在28 d较IVH组均显著降低.结论 去铁敏治疗可降低大鼠IVH后慢性脑积水发生率,Wnt信号通路参与了IVH后脑积水发生及去铁敏干预机制.

Abstract：

Objective To observe the effect of deferoxamine on chronic hydrocephalus after intraventricular hemorrhage (IVH) and the role of Wnt (Wnt1 and Wnt3a). Methods A total of 130Sprague Dawley male rats were randomly assigned into 4 groups: normal control group, sham - IVH group,IVH group and deferoxamine - treated group. The rats of subgroups except normal control group received an injection of autologous blood or saline into right lateral cerebral ventricles. Deferoxamine or vehicle was administered 3 hours after IVH and then every 12 hours up to 7 days in IVH group and deferoxaminetreated group. Rats were euthanized at 1, 7, 28 days for measurement, and the transverse diameter of the lateral ventricles were observed for evaluation of hydrocephalus. The expression of Wnt1 and Wnt3a were measured by RT -PCR and Western Blot. Results At 28 days, there was no hydrocephalus in the normal control group and sham - IVH group. 80 %(12/15) of the rats in IVH group developed hydrocephalus. The rate was only 20 % ( 3/15 ) in deferoxamine - treated group, which was much lower than that in IVH group. The expression of Wnt1 mRNA was normal in normal control group and shame - IVH group, and upregulated in IVH group. The peak expression was detected at 28 days. The expression was significantly higher than that in shame - IVH group at 7 days and 28 days, after deferoxamine treatment, downregulation of Wnt1 mRNA were observed and were significantly lower than that in IVH group. The Wnt3a mRNA had similar trends, while the expressed level was normal in normal control group and shame - IVH group, and upregulated following IVH. The peak expression was detected at 28 days, and was significantly higher than that in shame - IVH group at 7 days and 28 days. After deferoxamine treatment, the downregulation of Wnt3a mRNA was observed and was significantly lower than that in IVH group. Accordingly, Wnt1 protein expression was normal in normal control group and shame - IVH group, and increased after IVH. At 7 days and 28 days, the Wnt1 protein expression of IVH group was markedly higher than shame - IVH group. After deferoxamine treatment, the expression of Wnt1 protein was reduced and significantly lower than that of IVH group. The expression of Wnt3a protein was also normal in normal control group and shame - IVH group. The up-regulation of the protein expression was observed following IVH at 28 days, while down - regulation was observed after deferoxamine treatment at 28 days. Conclusions Deferoxamine could reduce hydrocephalus after IVH, and Wnt pathway may play an important role in the development of IVH and therapeutic effect of deferoxamine.     

去铁敏对大鼠脑室出血后慢性脑积水与脑组织Wnt1、Wnt3a表达的影响

目的 观察去铁敏对大鼠脑室出血(IVH)后脑积水的干预效果及脑组织Wnt1、Wnt3a的表达影响.方法 雄性SD大鼠130只随机分为正常组、假性IVH组、IVH组及IVH加去铁敏组.采用脑室出血后慢性脑积水大鼠模型,于术后1 d、7 d及28 d处死大鼠,观察脑积水的发生率和脑组织中Wnt基因及蛋白表达情况.结果 正常组、假性IVH组未见脑积水发生,IVH组28 d脑积水发生率80%(12/15),显著高于IVH加去铁敏组28 d脑积水发生率20%(3/15).IVH后Wnt1、Wnt3amRNA及蛋白表达在7 d及28 d均显著高于假性IVH组,而去铁敏治疗组Wnt1、Wnt3a mRNA及蛋白表达在28 d较IVH组均显著降低.结论 去铁敏治疗可降低大鼠IVH后慢性脑积水发生率,Wnt信号通路参与了IVH后脑积水发生及去铁敏干预机制.     

Influence of deferoxamine on hydrocephalus after intraventricular hemorrhage and expressions of Wnt1 and Wnt3a in rat

<正>Objective To observe the effect of deferoxamine on chronic hydrocephalus after intraventricular hemorrhage (IVH) and the role of Wnt (Wnt1 and Wnt3a) . Methods A total of 130 Sprague Dawley male rats were randomly assigned into 4 groups: normal control group, sham IVH group,IVH group and deferoxamine-treated group.     

去铁敏对大鼠脑室出血后慢性脑积水与脑组织Wnt1、Wnt3a表达的影响

目的 观察去铁敏对大鼠脑室出血(IVH)后脑积水的干预效果及脑组织Wnt1、Wnt3a的表达影响.方法 雄性SD大鼠130只随机分为正常组、假性IVH组、IVH组及IVH加去铁敏组.采用脑室出血后慢性脑积水大鼠模型,于术后1 d、7 d及28 d处死大鼠,观察脑积水的发生率和脑组织中Wnt基因及蛋白表达情况.结果 正常组、假性IVH组未见脑积水发生,IVH组28 d脑积水发生率80%(12/15),显著高于IVH加去铁敏组28 d脑积水发生率20%(3/15).IVH后Wnt1、Wnt3amRNA及蛋白表达在7 d及28 d均显著高于假性IVH组,而去铁敏治疗组Wnt1、Wnt3a mRNA及蛋白表达在28 d较IVH组均显著降低.结论 去铁敏治疗可降低大鼠IVH后慢性脑积水发生率,Wnt信号通路参与了IVH后脑积水发生及去铁敏干预机制.     

大鼠脑室出血后脑铁代谢与脑积水发生关系的研究

目的 观察脑室出血后铁离子和铁蛋白的动态变化,及去铁敏治疗前后慢性脑积水的发生率.方法 SD雄性大鼠170只,随机分为5组:正常对照组、假性脑室出血组、脑室出血组、侧脑室注铁离子组及脑室出血加去铁敏组.以前肉后0.4 mm冠状面的侧脑室宽度评价脑积水的发生率,以亚铁嗪法测量大鼠脑脊液铁离子含量,以ELISA试剂盒测量脑组织铁蛋白含量.结果 正常对照组、假性脑室出血组无脑积水发生,脑室出血组、侧脑室注铁离子组、脑室出血加去铁敏组28 d时脑积水发生率分别为80％、73％、20％,脑室出血加去铁敏组脑积水发生率显著低于脑室出血组和侧脑室注铁离子组(P＜0.01).脑脊液中铁离子含量和脑组织中铁蛋白在脑室出血组和侧脑室注铁离子组中各个时相点均显著高于假性脑室出血组(P＜0.01);脑室出血加去铁敏组铁离子含量在各个时相点,及铁蛋白在7、28d时均显著低于脑室出血组(P＜0.01).结论 大鼠脑室出血后脑脊液和脑组织铁含量明显升高,去铁敏可降低脑脊液中铁离子和脑组织中铁蛋白含量,降低脑积水的发生率.     

Wnt信号通路与纤维化

Wnt信号通路分为正规通路和非正规通路,是重要的细胞信号转导途径,该通路参与了从胚胎到成体的一系列控制胚胎早期发育,决定细胞分化、增殖及生长的调控,异常表达或激活该信号途径会导致多种疾病甚至肿瘤发生。最近研究表明Wnt信号通路与全身多种器官的组织细胞活化及组织纤维化发生相关。深入研究Wnt信号通路在组织纤维化尤其是蛛网膜纤维化发生中的作用,将有助于进一步揭示蛛网膜纤维化的发生机制,为蛛网膜纤维化及出血后慢性脑积水的防治提供新的可能途径及干预靶点。     

模拟急进高原环境下小型猪创伤性脑出血模型的建立

目的建立模拟急进高原环境下的实验用小型猪创伤性脑出血的动物模型。方法按随机数字表法将29只小型猪分为高原注血组(n=11)、高原假手术组(n=4)、平原注血组(n=11)和平原假手术组(n=3)。用动物低压氧舱模拟高原环境,采用二次法缓慢注射3 ml自体动脉血于右侧基底节区建立脑出血模型,立即行头颅CT扫描,分别于注血后各时相点(2、24、72、168 h)连续监测动脉血血气、动物行为学,168 h后行脑组织大体切片并计算血肿体积,行HE、Nissl染色,了解模型建立的稳定性及可重复性。结果 CT扫描、脑组织大体切片均显示脑内血肿形成,168 h后血肿体积明显减小(P<0.01),但高、平原两组血肿体积差异无统计学意义(P>0.05)。致伤后,在各时相点,高原注血组神经功能得分均大于平原注血组(P<0.01),且平、高原两注血组的主要血气参数值差异也均有统计学意义(P<0.01)。高原组的神经元细胞核、尼氏体的损伤及缺血改变重于平原组。结论本实验制备的高原创伤性脑出血模型能产生稳定的的血肿体积、明显的神经功能缺损,可操作性强、可重复性好。