Metabolic memory in diabetes - from in vitro oddity to in vivo problem: role of apoptosis.
Metabolic memory in diabetes - from in vitro oddity to in vivo problem: role of apoptosis.
复制标题
糖尿病的代谢记忆 - 从体外奇怪到体内问题：凋亡的作用。
DOI：
10.1016/j.brainresbull.2009.05.006
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发表时间：
2010-02-15
影响因子：
3.8
通讯作者：
Chan, Pooi-See
中科院分区：
文献类型：
--
作者：
Kowluru, Renu A.;Chan, Pooi-See
视网膜毛细血管细胞凋亡是视网膜病变发生前的一个重要病理过程，凋亡毛细血管细胞的出现可以预测视网膜病变的发展。本研究旨在探讨高血糖逆转对视网膜毛细血管细胞凋亡的影响，并鉴定凋亡相关基因。将链脲佐菌素糖尿病大鼠维持在较差的血糖控制（PC，糖化血红蛋白，GHb >11%）或良好的血糖控制（GC，GHb <6%）下12个月，或允许在PC下6个月，随后在GC下另外6个月（PC-GC）。用TUNEL法检测胰蛋白酶消化的视网膜微血管中毛细血管细胞凋亡，用Oligo GEArray大鼠凋亡基因芯片检测113个基因的表达。6个月血糖控制良好，随后6个月血糖控制不佳，未能减少视网膜微血管中TUNEL阳性毛细血管细胞的数量。23个视网膜基因，主要来自TNF配体和受体，半胱天冬酶，Bcl-2和死亡结构域亚家族，在PC大鼠中上调至少两倍，在高血糖逆转后仍然上调。因此，细胞凋亡的持续激活在恢复良好的血糖控制后视网膜病变停止的抵抗中起主要作用，并且调节细胞凋亡机制可以帮助延缓糖尿病视网膜病变的进展。
Retinal capillary cells undergo apoptosis before pathology characteristic of retinopathy can be observed, and the appearance of apoptotic capillary cell can predict the development of pathology. The purpose of this study is to investigate the effect of reversal of hyperglycemia on retinal capillary cell apoptosis, and identify the apoptosis encoding genes. Streptozotocin-diabetic rats were maintained either in poor glycemic control (PC, glycated hemoglobin, GHb >11%) or in good glycemic control (GC, GHb <6%) for 12 months, or allowed to be in PC for 6 months followed by GC for 6 additional months (PC–GC). Capillary cell apoptosis was determined in the trypsin-digested retinal microvasculature by TUNEL staining, and the genes encoding apoptosis were identified by Oligo GEArray rat apoptosis microarray that profiles 113 genes. Six months of good glycemic control that followed 6 months of poor control failed to attenuate the number of TUNEL-positive capillary cells in the retinal microvasculature. Twenty-three retinal genes, mainly from TNF ligand and receptor, caspase, Bcl-2 and death domain subfamilies that were upregulated by least a two-fold in PC rats remain upregulated after reversal of hyperglycemia. Thus, the continued activation of apoptosis plays a major role in the resistance of retinopathy to halt after re-institution of good glycemic control, and the regulation apoptosis machinery could help retard the progression of diabetic retinopathy.
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影响因子：
--
作者：
Kern, Timothy S.
通讯作者：
Kern, Timothy S.
影响因子：
15.9
作者：
Mizutani, M;Kern, TS;Lorenzi, M
通讯作者：
Lorenzi, M
影响因子：
15.9
作者：
Barber, AJ;Lieth, E;Gardner, TW
通讯作者：
Gardner, TW
影响因子：
3.8
作者：
Kowluru, RA;Chakrabarti, S;Chen, S
通讯作者：
Chen, S
影响因子：
7.7
作者：
Kowluru, RA
通讯作者：
Kowluru, RA