Exaggerated neutrophil-mediated reperfusion injury after ischemic stroke in a rodent model of type 2 diabetes.
Exaggerated neutrophil-mediated reperfusion injury after ischemic stroke in a rodent model of type 2 diabetes.
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DOI：
10.1111/j.1549-8719.2011.00115.x
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发表时间：
2011-10
期刊：
影响因子：
--
通讯作者：
Funk JL
中科院分区：
文献类型：
--
作者：
Ritter L;Davidson L;Henry M;Davis-Gorman G;Morrison H;Frye JB;Cohen Z;Chandler S;McDonagh P;Funk JL
在T2 DM的实验模型中，我们验证了慢性和急性炎症过程都会导致更严重的再灌注损伤和卒中结局的假设。12~13周龄雄性Zucker糖尿病肥胖大鼠(ZDF)和Zucker Lean对照组(ZLC)大鼠在基线和大脑中动脉阻塞(I-R)和再灌注(I-R)后进行测试。检测中性粒细胞与脑微循环的黏附、中性粒细胞CD11b的表达、脑梗塞面积、脑水肿、神经功能、sICAM和脑组织中性粒细胞-内皮细胞炎症基因的表达。在基线状态下，ZDF组与ZLC组相比CD11b和sICAM显著升高(p<；0.05)。缺血再灌注后，ZDF组中性粒细胞黏附和细胞聚集明显多于ZLC组(p<；0.05)；脑梗塞面积、水肿和神经功能明显低于ZLC组(p<；0.05)。再灌流2.5h后，ZDF组CD11b和sICAM-1表达显著增加(P<0.05)，IL-1β、GRO/KC、E-选择素和sICAM表达显著增加，而ZLC组未见明显变化(P>0.05)。在T2 DM的实验模型中，中性粒细胞-内皮细胞界面的两侧似乎在I-R之前被激活，并在I-R期间保持显著更高的活性。因此，再灌注损伤似乎在T2 DM患者不良的卒中结局中起着重要作用。
We tested the hypothesis that both chronic and acute inflammatory processes contribute to worse reperfusion injury and stroke outcome in an experimental model of T2DM. Twelve- to thirteen-week-old male Zucker Diabetic Fatty (ZDF) rats vs. Zucker Lean Controls (ZLC) rats were tested at baseline and after middle cerebral artery occlusion (ischemia) and reperfusion (I–R). Neutrophil adhesion to the cerebral microcirculation, neutrophil expression of CD11b, infarction size, edema, neurologic function, sICAM, and cerebral expression of neutrophil–endothelial inflammatory genes were measured. At baseline, CD11b and sICAM were significantly increased in ZDF vs. ZLC animals (p < 0.05). After I–R, significantly more neutrophil adhesion and cell aggregates were observed in ZDF vs. ZLC (p < 0.05); infarction size, edema, and neurologic function were significantly worse in ZDF vs. ZLC (p < 0.05). CD11b and sICAM-1 remained significantly increased in ZDFs (p < 0.05), and cerebral expression of IL-1β, GRO/KC, E-selectin, and sICAM were significantly induced in ZDF, but not ZLC groups (p < 0.05) after 2.5 hours of reperfusion. Both sides of the neutrophil–endothelial interface appear to be primed prior to I–R, and remain significantly more activated during I–R in an experimental model of T2DM. Consequently, reperfusion injury appears to play a significant role in poor stroke outcome in T2DM.
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影响因子：
4
作者：
Ergul, Adviye;Li, Weiguo;Elgebaly, Mostafa M.;Bruno, Askiel;Fagan, Susan C.
通讯作者：
Fagan, Susan C.
影响因子：
7.5
作者：
Cohen, Z;Gonzales, RF;McDonagh, PF
通讯作者：
McDonagh, PF
影响因子：
5.3
作者：
McColl, Barry W.;Rothwell, Nancy J.;Allan, Stuart M.
通讯作者：
Allan, Stuart M.
影响因子：
--
作者：
Almdal, T;Scharling, H;Vestergaard, H
通讯作者：
Vestergaard, H
影响因子：
6.3
作者：
MATSUO, Y;KIHARA, T;KOGURE, K
通讯作者：
KOGURE, K