Selective A2A adenosine receptor activation reduces skin pressure ulcer formation and inflammation
Selective A2A adenosine receptor activation reduces skin pressure ulcer formation and inflammation
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DOI：
10.1152/ajpheart.2001.281.1.h67
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发表时间：
2001-07-01
影响因子：
4.8
通讯作者：
Linden, J
中科院分区：
文献类型：
--
作者：
Peirce, SM;Skalak, TC;Linden, J
ATL-146 e（以前称为DWH-146 e）激活A（2A）腺苷受体（A（2A）-AR）可防止炎性细胞活化和粘附。皮肤的反复缺血-再灌注（I/R）导致压疮形成，这是一个主要的临床问题。在一种新的可重复大鼠压疮模型中评价ATL-146 e。使用手术植入的金属板和覆盖的磁体在50 mmHg下循环压缩大鼠背部皮肤的9 cm（2）区域，以产生可再现的组织坏死。将渗透微型泵植入24只大鼠中，分成4个相等的组，以输注载体（对照）、ATL-146 e（0.004 μ g. kg（-1）。min（-1））、ATL-146 e加等摩尔浓度的A（2A）拮抗剂、ZM-241385或单独的ZM-241385。每组接受10个I/R周期。在非I/R处理的皮肤中，ATL-146 e对血流没有影响。与溶剂组相比，ATL-146 e组的I/R处理皮肤坏死面积减少65%，平均皮肤血流抑制减少31%，外渗白细胞减少（每500 mum 23 +/- 3 vs. 49 +/- 6（2））。这些数据表明ATL-146 e通过A（2A）-AR起作用，减少白细胞浸润，并且是皮肤中I/R损伤的有效预防剂。
Activation of A(2A) adenosine receptors (A(2A)-AR) by ATL-146e (formerly DWH-146e) prevents inflammatory cell activation and adhesion. Recurrent ischemia-reperfusion (I/R) of the skin results in pressure ulcer formation, a major clinical problem. ATL-146e was evaluated in a novel reproducible rat model of pressure ulcer. A 9-cm(2) region of dorsal rat skin was cyclically compressed at 50 mmHg using a surgically implanted metal plate and an overlying magnet to generate reproducible tissue necrosis. Osmotic minipumps were implanted into 24 rats divided into four equal groups to infuse vehicle (control), ATL-146e (0.004 mug . kg(-1) . min(-1)), ATL-146e plus an equimolar concentration of A(2A) antagonist, ZM-241385, or ZM-241385 alone. Each group received 10 I/R cycles. In non-I/R-treated skin, ATL-146e has no effect on blood flow. I/R-treated skin of the ATL-146e group compared with the vehicle group had 65% less necrotic area, 31% less inhibition of average skin blood flow, and fewer extravasated leukocytes (23 +/- 3 vs. 49 +/- 6 per 500 mum(2)). These data suggest that ATL-146e, acting via an A(2A)-AR, reduces leukocyte infiltration and is a potent prophylactic for I/R injury in skin.