Resistance of retinal inflammatory mediators to suppress after reinstitution of good glycemic control: novel mechanism for metabolic memory.
Resistance of retinal inflammatory mediators to suppress after reinstitution of good glycemic control: novel mechanism for metabolic memory.
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DOI：
10.1016/j.jdiacomp.2008.10.002
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发表时间：
2010-01
影响因子：
3
通讯作者：
Kowluru RA
中科院分区：
文献类型：
--
作者：
Chan PS;Kanwar M;Kowluru RA
糖尿病性视网膜病变在血糖控制不良的一段时间后重新建立良好的血糖控制后，其进展会受到抑制。本研究旨在阐明炎症反应在高血糖终止后视网膜病变阻止中的作用。将链脲佐菌素糖尿病大鼠维持在血糖控制不良（PC，糖化血红蛋白，GHb>11%）或血糖控制良好（GC，GHb<7%）12个月，或允许在PC中6个月，随后在GC中另外6个月。在12个月时，分析视网膜的促炎介质。与正常大鼠视网膜相比，12个月的PC使视网膜白细胞介素-1 β（IL-1β）mRNA增加2倍，其蛋白表达增加25%。肿瘤坏死因子-α（TNF-α）升高约3倍（mRNA和蛋白质），IL-1β和TNF-α受体均增加40%。细胞间粘附分子-1（ICAM-1）和血管细胞粘附分子-1（VCAM-1）的浓度分别升高了40%和150%，iNOS转录物升高了6倍。6个月的GC和6个月的PC未能逆转IL-1β、TNFR 1和ICAM-1的升高;对TNF-α、iNOS和VCAM-1有一些有益的影响，但这些介质仍然显著升高。然而，GC组与正常大鼠相比，视网膜促炎介质没有显着变化。未能逆转视网膜炎性介质支持其在高血糖停止后视网膜病变停止抵抗中的重要作用。
Diabetic retinopathy resists arrest of its progression after reestablishment of good glycemic control that has followed a profound period of poor glycemic control. This study is to elucidate the role of inflammation in the resistance of retinopathy to arrest after termination of hyperglycemia. Streptozotocin-diabetic rats were maintained either in poor glycemic control (PC, glycated hemoglobin, GHb>11%) or in good glycemic control (GC, GHb<7%) for 12 months, or allowed to be in PC for six months followed by GC for six additional months. At 12 months, retina was analyzed for pro-inflammatory mediators. Twelve months of PC increased retinal interleukin-1β (IL-1β) mRNA by 2-fold and its protein expressions by 25% compared to the values obtained from normal rat retina. Tumor necrosis factor-α (TNF-α) was elevated approximately 3 fold (both mRNA and protein), and the receptors for IL-1β and TNF-α were increased by 40% each. The concentrations of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were elevated by 40% and 150% respectively, and iNOS transcripts by six fold. Six months of GC that followed six months of PC failed to reverse the elevations in IL-1β, TNFR1 and ICAM-1; and had some beneficial effects on TNF-α, iNOS and VCAM-I, but these mediators remained significantly elevated. However, GC group showed no significant changes in the retinal pro-inflammatory mediators compared to the normal rats. Failure to reverse retinal inflammatory mediators supports their important role in the resistance of retinopathy to arrest after cessation of hyperglycemia.
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影响因子：
--
作者：
Kern, Timothy S.
通讯作者：
Kern, Timothy S.
影响因子：
4.4
作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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