银杏双黄酮对大鼠脑缺血再灌注损伤时局部微血管及神经功能缺损的影响
Effects of ginkgetin on local microvascular and nerve function defects during cerebral ischemia/reperfusion injury in rats
陈超 1程广清 1李长生 1王爱帅 1王安荣 1杨晓妮1
作者信息
- 1. 山东第一医科大学第一附属医院(山东省千佛山医院),山东 济南 250014
- 折叠
摘要
目的:探讨银杏双黄酮对脑缺血/再灌注(ischemia/reperfusion,I/R)所致神经功能损伤和血管新生的影响及潜在机制.方法:60只SD大鼠随机分为假手术组、I/R模型组、银杏双黄酮(40 mg/kg)处理组,每组 20只.采用大脑中动脉闭塞/再灌注(middle cerebral artery occlusion/reperfusion,MCAO/R)大鼠模型模拟脑I/R,且在再灌注后连续注射银杏双黄酮 7 d.TTC染色测定各组大鼠脑梗死体积.通过尼氏染色和神经元特异性核蛋白(neuron-specific nuclear protein,NeuN)免疫组织化学分析各组大鼠缺血半暗带中的神经元密度.CD31标记法与BrdU/血管性血友病因子(von willebrand factor,vWF)双标免疫荧光染色法分析各组大鼠缺血半暗带中微血管密度和血管新生情况.Western blot检测各组大鼠缺血半暗带中热休克蛋白70(heat shock protein 70,HSP70)、血管内皮生长因子(vascular endothelial growth factor,VEGF)和缺氧诱导因子1α(hypoxia inducible factor-1α,HIF-1α)的水平.结果:与I/R模型组比较,银杏双黄酮处理组脑梗死体积显著变小(P<0.01),缺血半暗带中神经元、微血管密度和血管新生以及HIF-1α、VEGF和HSP70表达水平显著增高(P<0.01).结论:银杏双黄酮能促进MCAO大鼠血管新生和神经功能恢复,并上调缺血半暗带中HSP70、VEGF和HIF-1α的表达.
Abstract
AIM:To investigate the effects of ginkgetin on neurological deficit and angiogenesis induced by cerebral ischemia/reperfusion(I/R)and its underlying mechanism.METHODS:Sixty SD rats were randomly allocated into three groups:sham group,I/R model group,and ginkgetin(40 mg/kg)treatment(I/R+ginkgetin)group,with twenty rats in each group.The middle cerebral artery occlusion/reperfusion(MCAO/R)rat model was employed to simulate cere-bral I/R,and ginkgetin was administered continuously for 7 days following reperfusion.The cerebral infarction volume was quantified using TTC staining.Neuronal density in the ischemic penumbra was assessed through Nissl staining and immu-nohistochemistry for neuron-specific nuclear protein(NeuN).Microvessel density and angiogenesis in the ischemic pen-umbra of each group were analyzed using CD31 labeling and BrdU/von willebrand factor(vWF)double labeling immuno-fluorescence staining.Western blot analysis was performed to determine the levels of heat shock protein 70(HSP70),vas-cular endothelial growth factor(VEGF),and hypoxia inducible factor-1α(HIF-1α)in the ischemic penumbra.RE-SULTS:Compared with the I/R model group,the cerebral infarction volume was significantly reduced in ginkgetin treat-ment group(P<0.01),the number of neurons,the microvessel density,angiogenesis and the expression levels of HIF-1α,VEGF,and HSP70 in the ischemic penumbra were significantly increased(P<0.01).CONCLUSION:Ginkgetin exhibits the potential to augment angiogenesis and facilitate neurological function recovery in MCAO rats,while concur-rently upregulating the expression of HSP70,VEGF,and HIF-1α within the ischemic penumbra.
关键词
银杏双黄酮/缺血性脑卒中/缺血/再灌注/神经保护/血管新生Key words
Ginkgetin/Ischemic stroke/Ischemia/reperfusion/Neuroprotection/Angiogenesis引用本文复制引用
基金项目
山东省自然科学基金面上项目(ZR2021MH386)
山东省自然科学基金联合基金项目(ZR2021LZY028)
山东省千佛山医院国家自然科学基金培育基金(QYPY2020NSFC0619)
出版年
2024
国家科技期刊平台
NSTL
万方数据