Inhibition of 20-HETE attenuates diabetes-induced decreases in retinal hemodynamics.
Inhibition of 20-HETE attenuates diabetes-induced decreases in retinal hemodynamics.
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DOI：
10.1016/j.exer.2011.05.011
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发表时间：
2011-07
影响因子：
3.4
通讯作者：
Harris, Norman R.
中科院分区：
文献类型：
--
作者：
Wang, Zhongli;Yadav, Amit Singh;Leskova, Wendy;Harris, Norman R.
早期糖尿病引起的视网膜血流量减少的机制尚未完全确定。本研究的目的是探讨 20-羟基二十碳四烯酸 (20-HETE) 在糖尿病小鼠视网膜血流动力学早期下降中发挥作用的假设。 20-HETE 以前曾被认为与糖尿病增强的肠系膜和肾血管血管收缩有关；然而，其在糖尿病视网膜微循环中的作用尚未得到研究。通过多次低剂量注射链脲佐菌素（STZ；50 mg/kg，连续 5 天）诱导糖尿病，然后约 2 周后，在接下来的 2 周内，每天对小鼠进行腹腔注射，加或不加 20-HETE 抑制剂 HET0016（2.5 mg/kg/天）。年龄匹配的非糖尿病小鼠作为对照。使用活体显微镜测量视网膜血管直径和进出视盘的供给小动脉和引流小静脉的红细胞（RBC）速度。根据这些值，计算壁剪切率和血流率。糖尿病导致红细胞速度、壁剪切率和血流率降低约 30-40%。在给予 HET0016 的小鼠中，这些下降幅度减弱至 5-10%。总之，20-HETE抑制剂HET0016能够减弱糖尿病引起的视网膜血流动力学变化。
The mechanisms of early diabetes-induced decreases in retinal blood flow have yet to be fully determined. The aim of this study was to explore the hypothesis that 20-hydroxyeicosatetraenoic acid (20-HETE) plays a role in the early decrease of retinal hemodynamics in diabetic mice. 20-HETE has been implicated previously in the diabetes-enhanced vasoconstriction of mesenteric and renal vessels; however, its role in the diabetic retinal microcirculation has not been investigated. Diabetes was induced by multiple low-dose injections of streptozotocin (STZ; 50 mg/kg for 5 consecutive days), then ~2 weeks later the mice were administered daily intraperitoneal injections with or without the 20-HETE inhibitor HET0016 (2.5 mg/kg/day) for the following 2 weeks. Non-diabetic age-matched mice were included as controls. Intravital microscopy was used to obtain measurements of retinal vascular diameters and red blood cell (RBC) velocities for the feed arterioles and draining venules extending out of and into the optic disk. From these values, wall shear rates and blood flow rates were calculated. Diabetes induced approximate 30–40% decreases in RBC velocity, wall shear rate, and blood flow rate. These decreases were attenuated to 5–10% in the mice given HET0016. In summary, the 20-HETE inhibitor HET0016 is able to attenuate the retinal hemodynamic changes induced by diabetes.
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DOI：
10.1124/dmd.108.023150
发表时间：
2008-11
期刊：
Drug metabolism and disposition: the biological fate of chemicals
影响因子：
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3.4
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