双嘧达莫口服治疗可限制人类的缺血再灌注损伤。
Oral therapy with dipyridamole limits ischemia-reperfusion injury in humans.
作者信息
Riksen Niels P, Oyen Wim J G, Ramakers Bart P, Van den Broek Petra H H, Engbersen Richard, Boerman Otto C, Smits Paul, Rongen Gerard A
机构信息
Department of Pharmacology-Toxicology, Radbound University Nijmegen Medical Center, 6500 HB Nijmegen, The Netherlands.
出版信息
Clin Pharmacol Ther. 2005 Jul;78(1):52-9. doi: 10.1016/j.clpt.2005.03.003.
BACKGROUND
Adenosine receptor stimulation induces several effects that could limit ischemia-reperfusion injury. We hypothesize that treatment with the nucleoside uptake inhibitor dipyridamole increases endogenous adenosine and limits ischemia-reperfusion injury in humans.
METHODS
Ischemia-reperfusion injury was studied in forearm skeletal muscle by technetium Tc 99m-labeled annexin A5 scintigraphy. Ischemia-reperfusion injury was induced by unilateral forearm ischemic exercise. Immediately on reperfusion, annexin A5 labeled with technetium Tc 99m was administered intravenously, and ischemia-reperfusion injury was expressed as the percentage difference in radioactivity between the experimental arm and the control arm 1 and 4 hours after reperfusion. Targeting was quantified in the region of the thenar muscle and forearm flexor muscles. This approach was used in 9 healthy male volunteers after a 1-week treatment with dipyridamole (200 mg, slow release, twice daily) and in 23 control subjects.
RESULTS
Dipyridamole treatment significantly reduced annexin A5 targeting in skeletal muscle compared with the control group (thenar region, 13% +/- 7% versus 22% +/- 15% at 1 hour after reperfusion and 9% +/- 6% versus 27% +/- 13% at 4 hours for dipyridamole and control groups, respectively [P = .01]; flexor region, 4% +/- 8% versus 7% +/- 6% at 1 hour after reperfusion and 1% +/- 4% versus 10% +/- 9% at 4 hours for dipyridamole and control groups, respectively [P = .01]).
CONCLUSIONS
One week of oral treatment with the nucleoside uptake inhibitor dipyridamole (200 mg, slow release, twice daily) significantly limits ischemia-reperfusion injury in humans in vivo, as assessed by technetium Tc 99m-labeled annexin A5 scintigraphy of forearm skeletal muscle.
背景
腺苷受体刺激可产生多种效应，这些效应可能限制缺血再灌注损伤。我们假设，使用核苷摄取抑制剂双嘧达莫进行治疗可增加内源性腺苷，并限制人类的缺血再灌注损伤。
方法
通过锝Tc 99m标记的膜联蛋白A5闪烁扫描术，研究前臂骨骼肌的缺血再灌注损伤。通过单侧前臂缺血运动诱导缺血再灌注损伤。再灌注时立即静脉注射锝Tc 99m标记的膜联蛋白A5，缺血再灌注损伤以再灌注后1小时和4小时实验侧与对照侧放射性的百分比差异表示。在大鱼际肌和前臂屈肌区域对靶向进行定量。9名健康男性志愿者在接受为期1周的双嘧达莫（200 mg，缓释，每日2次）治疗后采用此方法，23名对照受试者也采用此方法。
结果
与对照组相比，双嘧达莫治疗显著降低了骨骼肌中膜联蛋白A5的靶向性（大鱼际区域，再灌注后1小时，双嘧达莫组为13%±7%，对照组为22%±15%；4小时时，双嘧达莫组为9%±6%，对照组为27%±13%[P = 0.01]；屈肌区域，再灌注后1小时，双嘧达莫组为4%±8%，对照组为7%±6%；4小时时，双嘧达莫组为1%±4%，对照组为10%±9%[P = 0.01]）。
结论
通过前臂骨骼肌的锝Tc 99m标记的膜联蛋白A5闪烁扫描术评估，为期1周的口服核苷摄取抑制剂双嘧达莫（200 mg，缓释，每日2次）治疗可显著限制人体体内的缺血再灌注损伤。
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