Tan Guo-Jun, Zhu Yi-Fei, Cao Cui-Fang, Zhao Xiao-Yun, Ma Chang-Sheng, Yang Tian-Zhu
Department of Neurology, the 2nd Hospital of Hebei Medical University, Shijiazhuang, China.
Sheng Li Xue Bao. 2004 Oct 25;56(5):579-84.
In order to investigate the role of heme oxygenase-1 (HO-1) in the molecular mechanism of experimental allergic encephalomyelitis (EAE), which was induced by guinea pig spinal cord homogenate + complete freund adjuvant on Wistar rats, we observed the gene of HO-1 and its protein expression with reverse transcriptase polymerase chain reaction(RT-PCR) and immunohistochemistry 1, 7, 14, and 21 d after EAE induction in rats. The relationship between HO-1 and the symptoms of EAE was also observed. The results showed that the levels of HO-1 mRNA and its protein expression were very low in the brains of the control group, whereas they were enhanced gradually with pathological course in the brain and onsets of symptoms, signs of EAE. On day 7, the level of HO-1 mRNA reached the peak, but the expression level of HO-1 protein in the brains reached the peak on day 14. The immunoreactive cells of HO-1 were mainly located at the choroid plexuses and subfornical organ (SFO), as well as in regions around the "sleeve-like" lesion foci, all of which were coincident with the locations of lesions of EAE. The levels of HO-1 mRNA and its protein expression were lowered gradually on day 21, which were in parallel with the severities of symptoms and signs of EAE. After a specific inhibitor of HO-1, Snpp-9, was applied, both of the symptoms and pathological lesions of EAE in the rat brains were mitigated markedly. Therefore, these results may suggest that the dynamic changes of HO-1 mRNA and its protein expression are in parallel with the changes of symptoms and pathological lesions of EAE in the brain. In conclusion, the levels of HO-1 mRNA and its protein expression in brains may play an important role in the pathogenesis of EAE, and application of inhibitors of HO-1 may be one of the potential therapeutic ways for the prevention and treatment of EAE.
为了研究血红素加氧酶-1(HO-1)在豚鼠脊髓匀浆加完全弗氏佐剂诱导的Wistar大鼠实验性自身免疫性脑脊髓炎(EAE)分子机制中的作用,我们在大鼠EAE诱导后1、7、14和21天,采用逆转录聚合酶链反应(RT-PCR)和免疫组织化学方法观察HO-1基因及其蛋白表达情况。同时观察HO-1与EAE症状之间的关系。结果显示,对照组大鼠脑内HO-1 mRNA及其蛋白表达水平很低,而在EAE脑内随着病理进程及症状、体征的出现逐渐升高。在第7天,HO-1 mRNA水平达到峰值,而脑内HO-1蛋白表达水平在第14天达到峰值。HO-1免疫反应阳性细胞主要位于脉络丛和穹窿下器官(SFO),以及“袖套样”病变灶周围区域,这些均与EAE病变部位相符。在第21天,HO-1 mRNA及其蛋白表达水平逐渐降低,这与EAE症状和体征的严重程度呈平行关系。应用HO-1特异性抑制剂Snpp-9后,大鼠脑内EAE的症状和病理损伤均明显减轻。因此,这些结果可能提示HO-1 mRNA及其蛋白表达的动态变化与脑内EAE症状和病理损伤的变化呈平行关系。总之,脑内HO-1 mRNA及其蛋白表达水平可能在EAE发病机制中起重要作用,应用HO-1抑制剂可能是预防和治疗EAE的潜在治疗方法之一。