Protective effect of Col003 on the blood-brain barrier after cerebral ischemia-reperfusion injury in rats

Objective To investigate the protective effect of Col003, an inhibitor of heat shock protein 47 (HSP47) on the blood-brain barrier (BBB) after cerebral ischemia-reperfusion injury in rats and its possible mechanism. Methods The rats were randomly divided into sham group, model group, butylphthalide...

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Main Authors: XIE Yuliang, ZHOU Kejian, DENG Mengyu, XIE Xiaoyun, LIANG Tingting, LI Haoying, LIU Jingli
Format: Article
Language:zho
Published: Editorial Office of Journal of Guangxi Medical University 2025-04-01
Series:Guangxi Yike Daxue xuebao
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Online Access:https://journal.gxmu.edu.cn/article/doi/10.16190/j.cnki.45-1211/r.2025.02.006
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author XIE Yuliang
ZHOU Kejian
DENG Mengyu
XIE Xiaoyun
LIANG Tingting
LI Haoying
LIU Jingli
author_facet XIE Yuliang
ZHOU Kejian
DENG Mengyu
XIE Xiaoyun
LIANG Tingting
LI Haoying
LIU Jingli
author_sort XIE Yuliang
collection DOAJ
description Objective To investigate the protective effect of Col003, an inhibitor of heat shock protein 47 (HSP47) on the blood-brain barrier (BBB) after cerebral ischemia-reperfusion injury in rats and its possible mechanism. Methods The rats were randomly divided into sham group, model group, butylphthalide group, and Col003 group. The middle cerebral artery occlusion (MCAO) model in rats was constructed using the suture occlusion method to simulate cerebral ischemia-reperfusion injury. After removing the suture, the rats in the butylphthalide group were intraperitoneally injected with butylphthalide (5 mg/kg). The rats in the Col003 group were injected with Col003 (50 μmol/L) through the tail vein, and the frequency and duration of administration of both drugs were once a day for 3 consecutive days. In the sham group, only the common carotid artery was isolated. Western blotting was used to detect the expression level of HSP47 in the brain tissues of rats after cerebral ischemia-reperfusion injury. The degree of brain dysfunction and BBB damage was assessed using TTC staining, neurological motor function scores, and Evans blue permeability assays. The effects of Col003 on endothelialmesenchymal transformation (EndMT) induced by cerebral ischemia-reperfusion in rats were evaluated by detecting the expression of tight junction proteins (ZO-1, Occludin, Claudin5) and mesenchymal marker proteins (α-SMA, Collagen I) in rat brain tissues by using western blotting, so as to further explore the possible mechanism of Col003 affecting BBB injury after cerebral ischemia-reperfusion in rats. Results At 24 h and 72 h after cerebral ischemia-reperfusion, the expression level of HSP47 in the brain tissue of rats was significantly higher than that in the sham group (P < 0.0001). Compared with the model group, the neurological function scores (P < 0.05) and motor function scores (P < 0.01) of MCAO rats in butylphthalide group and Col003 group were significantly improved, the cerebral infarction area was significantly reduced (P < 0.0001), and the Evans blue permeability was significantly decreased (P < 0.0001). Compared with the model group, the expression of tight junction protein in the brain tissue of Col003 group was significantly increased (P < 0.01), and the expression of mesenchymal marker protein was significantly decreased (all P < 0.01). Conclusion Col003 can improve BBB injury after cerebral ischemia-reperfusion, and has a protective effect on BBB. Its protective effect on BBB may be achieved by inhibiting EndMT.
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spelling doaj-art-7a9e6dc430d94265ba209ec8e7a7f3e02025-08-20T02:15:20ZzhoEditorial Office of Journal of Guangxi Medical UniversityGuangxi Yike Daxue xuebao1005-930X2025-04-0142220220910.16190/j.cnki.45-1211/r.2025.02.006gxykdxxb-42-2-202Protective effect of Col003 on the blood-brain barrier after cerebral ischemia-reperfusion injury in ratsXIE Yuliang0ZHOU Kejian1DENG Mengyu2XIE Xiaoyun3LIANG Tingting4LI Haoying5LIU Jingli6Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, ChinaDepartment of Neurology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, ChinaDepartment of Neurology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, ChinaDepartment of Neurology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, ChinaDepartment of Neurology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, ChinaDepartment of Neurology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, ChinaDepartment of Neurology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, ChinaObjective To investigate the protective effect of Col003, an inhibitor of heat shock protein 47 (HSP47) on the blood-brain barrier (BBB) after cerebral ischemia-reperfusion injury in rats and its possible mechanism. Methods The rats were randomly divided into sham group, model group, butylphthalide group, and Col003 group. The middle cerebral artery occlusion (MCAO) model in rats was constructed using the suture occlusion method to simulate cerebral ischemia-reperfusion injury. After removing the suture, the rats in the butylphthalide group were intraperitoneally injected with butylphthalide (5 mg/kg). The rats in the Col003 group were injected with Col003 (50 μmol/L) through the tail vein, and the frequency and duration of administration of both drugs were once a day for 3 consecutive days. In the sham group, only the common carotid artery was isolated. Western blotting was used to detect the expression level of HSP47 in the brain tissues of rats after cerebral ischemia-reperfusion injury. The degree of brain dysfunction and BBB damage was assessed using TTC staining, neurological motor function scores, and Evans blue permeability assays. The effects of Col003 on endothelialmesenchymal transformation (EndMT) induced by cerebral ischemia-reperfusion in rats were evaluated by detecting the expression of tight junction proteins (ZO-1, Occludin, Claudin5) and mesenchymal marker proteins (α-SMA, Collagen I) in rat brain tissues by using western blotting, so as to further explore the possible mechanism of Col003 affecting BBB injury after cerebral ischemia-reperfusion in rats. Results At 24 h and 72 h after cerebral ischemia-reperfusion, the expression level of HSP47 in the brain tissue of rats was significantly higher than that in the sham group (P < 0.0001). Compared with the model group, the neurological function scores (P < 0.05) and motor function scores (P < 0.01) of MCAO rats in butylphthalide group and Col003 group were significantly improved, the cerebral infarction area was significantly reduced (P < 0.0001), and the Evans blue permeability was significantly decreased (P < 0.0001). Compared with the model group, the expression of tight junction protein in the brain tissue of Col003 group was significantly increased (P < 0.01), and the expression of mesenchymal marker protein was significantly decreased (all P < 0.01). Conclusion Col003 can improve BBB injury after cerebral ischemia-reperfusion, and has a protective effect on BBB. Its protective effect on BBB may be achieved by inhibiting EndMT.https://journal.gxmu.edu.cn/article/doi/10.16190/j.cnki.45-1211/r.2025.02.006heat shock protein 47col003ischemic strokeischemia-reperfusion injuryblood-brain barrierendothelial-mesenchymal transition
spellingShingle XIE Yuliang
ZHOU Kejian
DENG Mengyu
XIE Xiaoyun
LIANG Tingting
LI Haoying
LIU Jingli
Protective effect of Col003 on the blood-brain barrier after cerebral ischemia-reperfusion injury in rats
Guangxi Yike Daxue xuebao
heat shock protein 47
col003
ischemic stroke
ischemia-reperfusion injury
blood-brain barrier
endothelial-mesenchymal transition
title Protective effect of Col003 on the blood-brain barrier after cerebral ischemia-reperfusion injury in rats
title_full Protective effect of Col003 on the blood-brain barrier after cerebral ischemia-reperfusion injury in rats
title_fullStr Protective effect of Col003 on the blood-brain barrier after cerebral ischemia-reperfusion injury in rats
title_full_unstemmed Protective effect of Col003 on the blood-brain barrier after cerebral ischemia-reperfusion injury in rats
title_short Protective effect of Col003 on the blood-brain barrier after cerebral ischemia-reperfusion injury in rats
title_sort protective effect of col003 on the blood brain barrier after cerebral ischemia reperfusion injury in rats
topic heat shock protein 47
col003
ischemic stroke
ischemia-reperfusion injury
blood-brain barrier
endothelial-mesenchymal transition
url https://journal.gxmu.edu.cn/article/doi/10.16190/j.cnki.45-1211/r.2025.02.006
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