Combined prostaglandin E1 and lithium exert potent neuroprotection in a rat model of cerebral ischemia
Combined prostaglandin E1 and lithium exert potent neuroprotection in a rat model of cerebral ischemia
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前列腺素 E1 和锂的组合在脑缺血大鼠模型中发挥有效的神经保护作用
DOI：
10.1038/aps.2010.211
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发表时间：
2011-03-01
影响因子：
8.2
通讯作者：
Qin, Zheng-hong
中科院分区：
文献类型：
--
作者：
Sheng, Rui;Zhang, Li-sha;Qin, Zheng-hong
目的：观察前列腺素E1（PGE 1）与锂（Li）混合制剂（PGE 1 +Li）对脑缺血后脑损伤的影响。方法：采用永久性大脑中动脉闭塞（permanent middle cerebral artery occlusion，pMCAO）大鼠模型，制备脑缺血模型。在缺血损伤后立即用PGE 1、锂或PGE 1 +Li混合物单次静脉内给药治疗大鼠。在缺血损伤后24 h分析梗死体积和运动行为缺陷。结果：混合物（PGE122.6nmol/kg+ Li0.5mmol/kg）可减少局灶性脑缺血引起的脑梗死体积和神经功能缺损。此外，与单独的PGE 1或锂相比，混合物对脑缺血具有更大的神经保护作用。即使在缺血后3 h给药，该混合物也有效。PGE 1 +Li还显著上调细胞保护性HSP 70、GRP 78、HSP 60和Bcl-2蛋白水平，同时降低p53表达。结论：这些结果表明，PGE 1 +Li混合物的治疗窗口长达3 h，可用于临床治疗脑缺血。PGE 1 +Li混合物通过诱导HSPs和Bcl-2蛋白在中风后潜在地发挥保护作用。
Aim: To examine the effects of a mixed formulation composed of prostaglandin E1 and lithium (PGE1+Li mixture) on brain damage after cerebral ischemia. The effects of the mixture on protein expression of heat shock proteins (HSPs), p53, and Bcl-2 were also determined.Methods: Brain ischemia was induced with a permanent middle cerebral artery occlusion (pMCAO) in rats. Rats were treated with a single intravenous administration of PGE1, lithium or a PGE1+Li mixture immediately after the ischemic insult. The infarct volume and motor behavior deficits were analyzed 24 h after the ischemic insult. The protein levels of HSP70, glucose-regulated protein 78 (GRP78), HSP60, Bcl-2, and p53 in the striatum of the ipsilateral hemisphere were examined using immunoblotting.Results: The mixture (PGE1 22.6 nmol/kg+Li 0.5 mmol/kg) reduced infarct volume and neurological deficits induced by focal cerebral ischemia. Moreover, the mixture had a greater neuroprotective effect against cerebral ischemia compared with PGE1 or lithium alone. The mixture was effective even if it was administered 3 h after ischemia. PGE1+Li also significantly upregulated cytoprotective HSP70, GRP78, HSP60, and Bcl-2 protein levels, while decreasing p53 expression.Conclusion: These results demonstrated a PGE1+Li mixture with a therapeutic window of up to 3 h for clinical treatment of cerebral ischemia. The PGE1+Li mixture potentially exerts a protective effect after stroke through the induction of HSPs and Bcl-2 proteins.