摘要
目的通过观察实验性脑出血大鼠不同时间段铁的沉积颗粒与血红素加氧酶-1(HO-1)之间的动态变化及相关性,探讨脑出血后铁超载与HO-1之间的相关关系,分析HO-1在脑出血后铁超载情况下的可能作用机制。方法采用大鼠缓慢注射自体血制造脑出血模型,Perl's法观察不同组大鼠铁沉积,免疫组化及RT—PCR法观察HO-1表达变化。结果脑出血模型各组较同期手术对照组铁沉积显著增多,且以第7天最多,增高约21倍(P〈0.001);去铁胺干预后脑组织铁沉积含量显著减少,且以第7天最显著(P〈0.01);HO-1免疫阳性细胞以神经元为主;脑出血各组HO-1免疫阳性细胞数及第3、7、14天组HO-1 mRNA表达显著增多,且以第3、7天最高;干预第3、14天组与同期脑出血组比较,HO-1免疫阳性细胞数显著减少;干预第7、14天组与同期脑出血组比较,HO-1 mRNA表达显著减少。相关分析显示铁染色颗粒与HO-1 mRNA表达(r=0.647)、HO-1免疫阳性细胞(r=0.209)呈显著正相关。结论脑出血后铁超载可能诱导HO-1的表达,HO-1的上调可能具有双重作用,因此应用HO-1酶抑制剂干预脑出血时应慎重考虑其作用的双重性。
Objective To investigate whether iron mass induces HO-1 overexpression and explore the role of HO-1 in rat intracerebral hemorrhage (ICH). Methods In this study, 144 hydrated chloride aldehyde-anesthetized Sprague- Dawley rats were used, autologous blood were injected into the right caudate nucleus to establish the ICH model. Saline injection and health were served as controls. Deferoxamine(DFO) with an intraperitoneal injection served as intervention group. Enhanced Perl's reaction was used for iron staining and brain iron deposits were determined. Brain HO-1 level were examined by immunohistochemical analysis and reverse transcription polymerase chain reaction (RT-PCR). Results There was a 21-fold increase in iron deposits around the hematoma 7 days after the infusion of 100 μl of autologous blood. Markedly increased levels of perihematomal HO-1 immunoreactivity and HO-1 mRNA in all ICH rats were detected at 3-14 days. The addition of DFO significantly reduced iron deposits in the ipsilateral basal ganglia at 7-14 days after ICH. DFO also inhibited HO-1 overexpression at day 7, 14. Correlations test showed that there were positive correlations of iron sediments with HO-1 mRNA (r = 0. 647) and HO-1 immunopositive cells ( r = 0. 209). Conclusions ICH causes iron accumulation in the brain. Iron overloading may induce HO-1 upregulation afterICH. Ratherly, the HO-1 moderate increasing possibly fits with the events, whereas HO-1 overexpression may result in its dysfunction. It may be prudent to intervene ICH with HO-1 inhibitor.
出处
《中华老年医学杂志》
CAS
CSCD
北大核心
2008年第5期380-384,共5页
Chinese Journal of Geriatrics