15d-Prostaglandin J2 protects brain from ischemia-reperfusion injury
15d-Prostaglandin J2 protects brain from ischemia-reperfusion injury
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DOI：
10.1161/01.atv.0000201933.53964.5b
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发表时间：
2006-03-01
影响因子：
8.7
通讯作者：
Wu, KK
中科院分区：
文献类型：
--
作者：
Lin, TN;Cheung, WM;Wu, KK
目的：脑中表达丰富的Lipocalin型前列腺素D-2(PGD(2))合成酶，但PGD2及其代谢产物15-脱氧-Delta(12.14)-PGJ(2)(15d-PGJ(2))在脑保护中的作用尚不清楚。本研究的目的是评价15d-PGJ2的神经保护作用。方法和结果：利用环氧合酶-1的腺病毒转移技术，在大鼠局灶性脑梗塞模型中扩增缺血皮质中15d-PGJ2的产物。ADV-COX-1治疗组大鼠大脑皮质15d-PGJ2水平较对照组增加3倍，与脑梗塞体积缩小、caspase3激活、过氧化体增殖物激活受体-γ(PPAR-γ)和血红素氧合酶-1(HO-1)升高有关。脑室注射15d-PGJ2可使脑梗塞体积缩小，但这种作用可被PPAR-γ抑制剂消除。罗格列酮滴注也有类似的效果。15D-PGJ2和低浓度罗格列酮可抑制H_2O_2诱导的大鼠或人脑组织神经细胞的凋亡和坏死，并诱导PPAR-γ和HO-1的表达。结论-15d-PGJ(2)以PPARγ依赖的方式抑制缺血性脑梗塞和神经细胞的凋亡和坏死。15D-PGJ(2)可能对脑缺血再灌流所致的急性脑损伤有一定的控制作用。
Objective-Brain expresses abundant lipocalin-type prostaglandin (PG) D-2 (PGD(2)) synthase but the role of PGD2 and its metabolite, 15-deoxy-Delta(12.14) PGJ(2) (15d- PGJ(2)) in brain protection is unclear. The aim of this study is to assess the effect of 15d- PGJ2 on neuroprotection.Methods and Results-Adenoviral transfer of cyclooxygenase-1 (Adv-COX-1) was used to amplify the production of 15d- PGJ2 in ischemic cortex in a rat focal infarction model. Cortical 15d- PGJ2 in Adv-COX-1-treated rats was increased by 3-fold over control, which was correlated with reduced infarct volume and activated caspase 3, and increased peroxisome proliferator activated receptor-gamma (PPAR gamma) and heme oxygenase-1 (HO-1). Intraventricular infusion of 15d- PGJ2 resulted in reduction of infarct volume, which was abrogated by a PPAR gamma inhibitor. Rosiglitazone infusion had a similar effect. 15d- PGJ2 and rosiglitazone at low concentrations suppressed H2O2-induced rat or human neuronal apoptosis and necrosis and induced PPAR gamma and HO-1 expression. The anti-apoptotic effect was abrogated by PPAR gamma inhibition.Conclusion-15d-PGJ(2) suppressed ischemic brain infarction and neuronal apoptosis and necrosis in a PPAR gamma dependent manner. 15d-PGJ(2) may play a role in controlling acute brain damage induced by ischemia-reperfusion.