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。
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 cerebral 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 immunohistochemistry for neuron-specific nuclear protein(NeuN).Microvessel density and angiogenesis in the ischemic penumbra of each group were analyzed using CD31 labeling and BrdU/von willebrand factor(vWF)double labeling immunofluorescence staining.Western blot analysis was performed to determine the levels of heat shock protein 70(HSP70),vascular 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 treatment 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 concurrently upregulating the expression of HSP70,VEGF,and HIF-1αwithin the ischemic penumbra.
作者
陈超
程广清
李长生
王爱帅
王安荣
杨晓妮
CHEN Chao;CHENG Guangqing;LI Changsheng;WANG Aishuai;WANG Anrong;YANG Xiaoni(The First Affiliated Hospital of Shandong First Medical University(Shandong Provincial Qianfoshan Hospital),Jinan 250014,China)
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2024年第7期1261-1267,共7页
Chinese Journal of Pathophysiology
基金
山东省自然科学基金面上项目(No.ZR2021MH386)
山东省自然科学基金联合基金项目(No.ZR2021LZY028)
山东省千佛山医院国家自然科学基金培育基金(No.QYPY2020NSFC0619)。
