广西医科大学学报2025,Vol.42Issue(2):202-209,8.DOI:10.16190/j.cnki.45-1211/r.2025.02.006
Col003对大鼠脑缺血再灌注损伤后血脑屏障的保护作用
Protective effect of Col003 on the blood-brain barrier after cerebral ischemia-reperfusion in-jury in rats
摘要
Abstract
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 oc-clusion method to simulate cerebral ischemia-reperfusion injury.After removing the suture,the rats in the bu-tylphthalide 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 iso-lated.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 endothelial-mesenchymal transformation(EndMT)induced by cerebral ischemia-reperfusion in rats were evaluated by detect-ing 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 mecha-nism 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 signifi-cantly improved,the cerebral infarction area was significantly reduced(P<0.0001),and the Evans blue perme-ability 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 mesen-chymal 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.关键词
热休克蛋白47/Col003/缺血性卒中/缺血再灌注损伤/血脑屏障/内皮—间质转化Key words
heat shock protein 47/Col003/ischemic stroke/ischemia-reperfusion injury/blood-brain barrier/endothelial-mesenchymal transition分类
医药卫生引用本文复制引用
谢育良,周克剑,邓梦雨,谢晓云,梁婷婷,李浩英,刘竞丽..Col003对大鼠脑缺血再灌注损伤后血脑屏障的保护作用[J].广西医科大学学报,2025,42(2):202-209,8.基金项目
国家自然科学基金资助项目(No.82160236) (No.82160236)
广西自然科学基金资助项目(No.2023GXNSFDA026017) (No.2023GXNSFDA026017)