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.

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

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.