A(3) adenosine receptor activation during reperfusion reduces infarct size through actions on bone marrow-derived cells.
A(3) adenosine receptor activation during reperfusion reduces infarct size through actions on bone marrow-derived cells.
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DOI：
10.1016/j.yjmcc.2010.01.018
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发表时间：
2010-08
影响因子：
5
通讯作者：
Auchampach JA
中科院分区：
文献类型：
--
作者：
Ge ZD;van der Hoeven D;Maas JE;Wan TC;Auchampach JA
本研究的目的是在体内小鼠心肌梗死模型中，检验A3腺苷受体（A3AR）激动剂Cl - IB - MECA在再灌注时给药（冠状动脉闭塞30分钟及再灌注24小时诱导梗死）是否能预防心肌缺血/再灌注损伤。在再灌注阶段用Cl - IB - MECA治疗B6野生型小鼠（静脉推注100μg/kg + 通过植入Alzet微型渗透泵皮下给药0.3μg/kg/min），可使心肌梗死面积从溶媒处理小鼠的50.1±2.5%减少约37%，降至Cl - IB - MECA处理小鼠的31.6±2.8%，并显著减少浸润到缺血再灌注心肌的白细胞数量。在使用B6同基因A3AR基因“敲除”小鼠或骨髓（BM）来源细胞中缺乏A3AR表达的嵌合小鼠的研究中，Cl - IB - MECA没有减少梗死面积或限制白细胞聚集。后续机制研究表明，在跨孔迁移试验中，Cl - IB - MECA抑制从骨髓分离的小鼠中性粒细胞向趋化物质C5a的迁移，并在巯基乙酸盐诱导的腹膜炎小鼠模型中抑制白细胞迁移到腹腔。我们得出结论，在再灌注时用A3AR激动剂Cl - IB - MECA治疗，通过激活骨髓来源细胞中表达的A3AR，可能通过抑制再灌注期间发生的强烈炎症反应和中性粒细胞介导的组织损伤，为心脏提供有效的缺血/再灌注损伤保护。
The goal of this study was to examine whether the A3 adenosine receptor (A3AR) agonist Cl-IB-MECA protects against myocardial ischemia/reperfusion injury when administered at the time of reperfusion in an in vivo mouse model of infarction induced by 30 min of coronary occlusion and 24 h of reperfusion. Treating B6 wild-type with Cl-IB-MECA during the reperfusion phase (100 μg/kg i.v. bolus + 0.3 μg/kg/min subcutaneously via implantation of Alzet mini-osmotic pumps) reduced myocardial infarct size ~37% from 50.1 ± 2.5% in vehicle-treated mice to 31.6 ± 2.8% in Cl-IB-MECA-treated mice, and significantly reduced the number of leukocytes that infiltrated into the ischemic-reperfused myocardium. Cl-IB-MECA did not reduce infarct size or limit leukocyte accumulation in studies using B6 congenic A3AR gene “knock-out” mice or in chimeric mice lacking the expression of A3ARs in bone marrow (BM)-derived cells. Subsequent mechanistic studies demonstrated that Cl-IB-MECA inhibited migration of mouse neutrophils isolated from BM towards the chemotactic substance c5a in trans-well migration assays, and inhibited leukocyte migration into the peritoneal cavity in a mouse model of thioglycollate-induced peritonitis. We conclude that treating with the A3AR agonist Cl-IB-MECA at the time of reperfusion provides effective protection from ischemia/reperfusion injury in the heart through activation of the A3AR expressed in BM-derived cells, potentially by suppressing the robust inflammatory reaction that occurs during reperfusion and neutrophil-mediated tissue injury.
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DOI：
10.1084/jem.20061097
发表时间：
2006-11-27
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lappas CM;Day YJ;Marshall MA;Engelhard VH;Linden J
通讯作者：
Linden J
影响因子：
20.1
作者：
Black, RG;Guo, YR;Auchampach, JA
通讯作者：
Auchampach, JA
影响因子：
3.6
作者：
van der Hoeven, Dharini;Wan, Tina C.;Auchampach, John A.
通讯作者：
Auchampach, John A.
N6-(3-碘苄基)-腺苷-5′-N-甲基甲酰胺通过糖原合酶激酶 3β 抑制线粒体通透性转换孔开放，从而在再灌注时提供心脏保护作用
DOI：
10.1124/jpet.106.101477
发表时间：
2006-07-01
影响因子：
3.5
作者：
Park, Sung-Sik;Zhao, Hong;Xu, Zhelong
通讯作者：
Xu, Zhelong
影响因子：
10.8
作者：
Tracey, WR;Magee, W;Hill, RJ
通讯作者：
Hill, RJ