CAJ | 학술논문

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.
목적 통과관찰실험성뇌출혈대서불동시간단철적침적과립여혈홍소가양매-1(HO-1)지간적동태변화급상관성,탐토뇌출혈후철초재여HO-1지간적상관관계,분석HO-1재뇌출혈후철초재정황하적가능작용궤제.방법 채용대서완만주사자체혈제조뇌출혈모형,Perl's법관찰불동조대서철침적,면역조화급RT-PCR법관찰HO-1표체변화.결과 뇌출혈모형각조교동기수술대조조철침적현저증다,차이제7천최다,증고약21배(P＜0.001);거철알간예후뇌조직철침적함량현저감소,차이제7천최현저(P＜0.01);HO-1면역양성세포이신경원위주;뇌출혈각조HO-1면역양성세포수급제3、7、14천조HO-1 mRNA표체현저증다,차이제3、7천최고;간예제3、14천조여동기뇌출혈조비교,HO-1면역양성세포수현저감소;간예제7、14천조여동기뇌출혈조비교,HO-1 mRNA표체현저감소.상관분석현시철염색과립여HO-1 mRNA표체(r=0.647)、HO-1면역양성세포(r=0.209)정현저정상관.결론 뇌출혈후철초재가능유도HO-1적표체,HO-1적상조가능구유쌍중작용,인차응용HO-1매억제제간예뇌출혈시응신중고필기작용적쌍중성.
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-1mRNA(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 after ICH.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.