Hemopexin alleviates cognitive dysfunction after focal cerebral ischemia-reperfusion injury in rats
Hemopexin alleviates cognitive dysfunction after focal cerebral ischemia-reperfusion injury in rats
复制标题
血红素结合蛋白减轻大鼠局灶性脑缺血再灌注损伤后的认知功能障碍
DOI：
10.1186/s12871-019-0681-2
复制
发表时间：
2019-01-15
影响因子：
2.2
通讯作者：
Yu, Yonghao
中科院分区：
文献类型：
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作者：
Dong, Beibei;Yang, Yongyan;Yu, Yonghao
脑缺血再灌注（I/R）是脑缺血导致认知功能障碍的重要病理生理基础。血红素加氧酶-1 （HO-1）是通过与血红素（HPX）结合消除过量游离血红素的限速酶，HPX是一种有助于消除缺血卒中时过量游离血红素的血浆蛋白。本研究旨在阐明HPX是否能减轻脑I/R大鼠的认知功能障碍。方法将大鼠随机分为5组：sham组、MCAO组、Vehicle组、HPX组和HPX +原卟啉IX （ZnPPIX）组。MCAO诱导脑I/R。再灌注后即刻脑室内注射生理盐水、载药、HPX及HPX + ZnPPIX。Morris水迷宫（Morris water maze， MWM）测试大鼠的学习和认知功能。Western blot检测缺血半暗区HO-1的表达。采用CD31/vWF双标记免疫荧光法检测海马半暗区新生血管的形成。通过Evans Blue通透性（EB）、脑组织含水量、Ang1/Ang2及VE-cadherin表达检测血脑屏障（BBB）的结构和功能。结果我们的研究证实了HPX提高了学习和记忆能力。Hemopexin上调HO-1蛋白表达、海马半暗区平均血管密度和VE- cadherin表达，降低EB通透性、脑组织含水量和Ang1/Ang2比值。这种作用被HO-1抑制剂ZnPPIX逆转。结论hpx可通过HO-1通路维持脑I/R后血脑屏障的完整性，减轻脑I/R后认知功能障碍。
BackgroundIschemia-reperfusion (I/R) is a critical pathophysiological basis of cognitive dysfunction caused by ischemia stroke. Heme-oxygenase-1 (HO-1) is the rate-limiting enzyme for the elimination of excessive free heme by combining with hemopexin (HPX), a plasma protein that contributes to eliminating excessive free heme during ischemia stroke. This study aimed to elucidate whether HPX could alleviate cognitive dysfunction in rats subjected to cerebral I/R.MethodsRats were randomly divided into five groups: sham, MCAO, Vehicle, HPX and HPX + protoporphyrin IX (ZnPPIX). Cerebral I/R was induced by MCAO. Saline, vehicle, HPX and HPX + ZnPPIX were injected intracerebroventricularly at the moment after reperfusion. Morris water maze (MWM) test was used to detect the learning and cognitive function. Western blot was used to detect the expression of HO-1 in ischemic penumbra. CD31/vWF double labeling immunofluorescence was used to detect the neovascularization in the penumbra hippocampus. The structure and function of blood-brain barrier (BBB) was detected by the permeability of Evans Blue (EB), water content of the brain tissue, the Ang1/Ang2 and VE-cadherin expression.ResultsOur study verified that HPX improved the learning and memory capacity. Hemopexin up-regulated HO-1 protein expression, the average vessel density in the penumbra hippocampus and the VE- cadherin expression but decreased the permeability of EB, the water content of brain tissue and the ratio of Ang1/Ang2. The effects were reversed by ZnPPIX, an inhibitor of HO-1.ConclusionHPX can maintain the integrity of the blood-brain barrier and alleviate cognitive dysfunction after cerebral I/R through the HO-1 pathway.