脑血管内皮细胞miR-15a/16-1基因敲除对缺血性脑卒中后脑血流量变化的作用  

The impact of miR-15a/16-1 gene knockout in cerebral vascular endothelial cells on dynamic changes of cerebral blood flow after ischemic stroke

作　　者：熊天庆 朱虹 王兴仪 王英歌 XIONG Tianqing;ZHU Hong;WANG Xingyi;WANG Yingge(College of Medicine(Institute of Translational Medicine),Yangzhou University,Yangzhou 225009,China;Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases,Yangzhou 225009,China;Department of Neurology,Affiliated Hospital of Yangzhou University,Yangzhou 225009,China)

机构地区：[1]扬州大学医学院(转化医学研究院),江苏扬州225009 [2]江苏省中西医结合老年病防治重点实验室,江苏扬州225009 [3]扬州大学附属医院神经内科,江苏扬州225009

出　　处：《扬州大学学报(农业与生命科学版)》2024年第6期36-44,共9页Journal of Yangzhou University:Agricultural and Life Science Edition

基　　金：中国博士后科学基金资助项目(2022M712689);江苏省高等学校自然科学研究面上项目(22KJB180029);扬州市社会发展项目(YZ2023067);扬州大学医学创新转化专项基金“临床转化研究项目”(AHYZUZHXM202102);中华国际医学交流基金“脑血管病青年创新基金”项目(Z-2016-20-2101)。

摘　　要：为探讨miR-15a/16-1对脑血管内皮细胞功能的调控作用,及其对缺血性脑卒中后脑血流量和神经功能的影响,构建脑血管内皮细胞特异性miR-15a/16-1基因敲除小鼠,并建立小鼠大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)模型。采用TTC(2,3,5-triphenyte-trazoliumchloride)染色检测MCAO造模后小鼠脑梗死体积;利用激光散斑成像系统监测MCAO围手术期(术前、线栓插入后15 min和拆线后15 min)和术后长期脑血流量(cerebral blood flow,CBF)的变化情况;通过行为学试验评估MCAO造模后小鼠感觉功能障碍、运动功能障碍和学习记忆能力的缺损情况。结果表明:与野生型小鼠相比,miR-15a/16-1基因敲除小鼠在MCAO造模后24 h的脑梗死体积明显减小;虽然二者在MCAO造模围手术期的脑血流量无显著差异,但miR-15a/16-1基因敲除可提高术后14和21 d的脑血流量;相应地,miR-15a/16-1基因敲除小鼠在MCAO造模后的感觉功能障碍、运动功能障碍和神经功能缺损症状更轻。综上,脑血管内皮细胞miR-15a/16-1基因敲除能够减小脑梗死体积,部分促进缺血性脑卒中后脑血流量的恢复,并改善缺血性脑卒中后的神经功能缺损。The aim of this study was to investigate the regulatory effect of miR-15a/16-1 on the function of cerebral vascular endothelial cells and its effect on cerebral blood flow and neurological function after ischemic stroke.We constructed a mouse with a specific miR-15a/16-1 gene knockout in cerebral vascular endothelial cells,and established a model of middle cerebral artery occlusion(MCAO)in mice.TTC(2,3,5-triphenyte-trazoliumchloride)staining was used to detect the infarct volume after MCAO operation,cerebral blood flow changes in perioperative(preoperatively,15 minutes after plug insertion and 15 minutes after suture removal)and long-term postoperative periods were monitored by the laser speckle imaging system,and behavioral experiments were conducted to evaluate the sensory dysfunction,motor dysfunction and learning and memory deficits of mice post-MCAO.The results showed that compared with wild-type mice,the infarct volume in mice with miR-15a/16-1 gene deficiency was significantly reduced 24 h after MCAO modeling.Although there was no significant difference in cerebral blood flow between the two groups in the perioperative period,miR-15a/16-1 gene defect increased cerebral blood flow at 14 and 21 days after surgery.Correspondingly,miR-15a/16-1 gene deficient mice had milder sensory dysfunction,motor dysfunction and neurological deficit symptoms after MCAO modeling.In conclusion,miR-15a/16-1 gene defect in cerebral vascular endothelial cells can reduce the infarct volume,partially promote the recovery of cerebral blood flow after ischemic stroke,and improve neurological deficits after ischemic stroke.

关 键 词：脑血管内皮细胞 miR-15a/16-1 缺血性脑卒中 脑血流量 神经功能 

分 类 号：R743.3[医药卫生—神经病学与精神病学]