Heme oxygenase in the retina in diabetes
Heme oxygenase in the retina in diabetes
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DOI：
10.1076/ceyr.27.5.301.17227
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发表时间：
2003-11-01
影响因子：
2
通讯作者：
Chakabarti, S
中科院分区：
文献类型：
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作者：
Cukiernik, M;Mukherjee, S;Chakabarti, S
导论.血红素加氧酶（HO）亚型HO-1和HO-2负责血红素分解为铁和一氧化碳（CO）。HO可能响应氧化应激，并可能调节血管活性因子如一氧化氮（NO）的表达。由于糖尿病引起的氧化应激可改变HO，本研究探讨糖尿病是否与HO改变有关，其与NO，内皮素-1（ET-1）的关系及其功能意义。用链脲佐菌素诱导雄性SD大鼠糖尿病6周后进行研究。将控制不佳的糖尿病动物随机分为三个治疗组之一（每组n = 6）：a）未治疗，B）HO-1抑制剂SnPP-IX（50 μ mol/kgIP/天），c）NO供体吗西多明（120 mg/L PO/天），并与年龄和性别匹配的非糖尿病对照动物进行比较，用或不用SnPP-IX治疗。彩色多普勒超声检测视网膜电阻率指数（RI）。竞争性RT-PCR检测HO-1、HO-2、ET-1、eNOS和iNOS的mRNA表达。用免疫细胞化学方法观察HO在视网膜中的分布。糖尿病动物表现出较低的体重、较高的血糖和增加的糖化血红蛋白水平。HO-1和HO-2免疫反应性在视网膜中被鉴定。糖尿病引起的RI增加与ET-1和HO-1 mRNA表达上调有关，但与eNOS和iNOS mRNA表达无关。SnPP-IX和吗西多明治疗均阻止了糖尿病RI的增加，尽管ET-1表达增加，并且与iNOS mRNA增加相关。目前的数据表明，HO系统在短期糖尿病中上调，导致HO和NO相互作用，这可能调节视网膜中的血管功能。
Introduction. Heme oxygenase (HO) isoforms, HO-1, and HO-2, are responsible for heme breakdown to iron and carbon monoxide (CO). HO may respond to oxidative stress and may modulate the expression of vasoactive factors like nitric oxide (NO). Since diabetes induced oxidative stress may change HO, the present study examined whether diabetes is associated with HO alterations, its relationship with NO, endothelin-1(ET-1) and the functional significance.Materials & Methods. Male SD rats with Streptozotocin induced diabetes were investigated after six-weeks. Poorly controlled diabetic animals were randomized to one of three treatment groups (n = 6 each group); a) untreated, b) HO-1 inhibitor SnPP-IX (50 mumol/kgIP/day), c) NO donor molsidomine (120mg/L PO/day) and were compared with age and sex matched non diabetic control animals with or without SnPP-IX treatment. Color Doppler ultrasound analysis was used to determine retinal resistivity index (RI). mRNA for HO-1, HO-2, ET-1, eNOS and iNOS were analyzed with competitive RT-PCR. HO distribution in the retina was investigated by immunocytochemistry.Results. Diabetic animals expressed lower body weight, higher blood glucose and increased glycated hemoglobin levels. HO-I and HO-2 immuno-reactivity were identified in the retina. Diabetes induced increased RI was associated with up-regulation of both ET-1 and HO-I mRNA expression but not eNOS or iNOS mRNA. Both SnPP-IX and molsidomine treatments prevented a diabetes increase of RI, in spite of increased ET-1 expression and were associated with increased iNOS mRNA.Conclusions. The present data suggests that the HO system is up-regulated in short term diabetes leading to HO and NO interactions which may modulate vascular function in the retina.