长期运动基于TGF-β1/Smad3信号通路对脑卒中大鼠脑中血管新生的影响  

The effect of long-term exercise on angiogenesis in the brain of stroke rats based on TGF-β1/Smad3 signal pathway

作　　者：再努热·阿不拉汗[1] 阿依努尔·艾尼[1] 韩晶[1] ZAINUR Abraham;AINUR Aini;HAN Jing(Rehabilitation Department,People′s Hospital of Xinjiang Uygur Autonomous Region,Urumqi 833001,China)

机构地区：[1]新疆维吾尔自治区人民医院康复科,新疆乌鲁木齐833001

出　　处：《解剖科学进展》2023年第6期592-596,共5页Progress of Anatomical Sciences

基　　金：新疆维吾尔自治区自然科学基金(2020D01C17)。

摘　　要：目的 探讨长期运动对脑卒中大鼠血管新生与神经功能的影响。方法 48只大鼠随机分为对照组、脑卒中组、运动+脑卒中组、运动+抑制剂+脑卒中组,采用中动脉阻塞后再灌注操作构建脑卒中大鼠模型。分别于再灌注结束后1 d、3 d与7 d检测大鼠神经功能,随后取脑检测脑梗死体积,免疫荧光检测大鼠BrdU与CD31表达,Western blot检测TGF-β1,Smad与VEGF表达。结果 脑缺血再灌注模型造成各组大鼠出现不同程度的神经功能损伤,随着时间的进展,脑卒中与运动+脑卒中组大鼠神经功能逐渐改善。与脑卒中组相比,运动+脑卒中组大鼠脑梗死体积显著减少(P<0.05),神经功能评分显著降低(P<0.05)。长期运动显著提高了BrdU阳性细胞数,增加了CD31阳性表达(P<0.05),与此同时,上调了TGF-β1、p-Smad3与VEGF表达水平(P<0.05)。此外,与运动+脑卒中组相比,TGF-β1抑制剂的干预显著逆转了长期运动介导的BrdU与CD31表达增加(P<0.05),降低TGF-β1、p-Smad3与VEGF表达水平(P<0.05),最终导致神经元与神经血管内皮细胞增殖抑制(P<0.05),造成大鼠神经功能评分升高(P<0.05)。结论 长期运动通过TGF-β1/Smad3信号通路上调神经元与神经血管内皮细胞新生,减少缺血区脑梗死体积,对脑卒中大鼠发挥神经保护作用。Objective To investigate the effects of long-term exercise on angiogenesis and neurological function in stroke rats.Methods 48 rats were randomly divided into control group,stroke group,exercise+stroke group,exercise+inhibitor+stroke group.The middle artery occlusion and reperfusion operation was used for stroke model.The neurological function of rats was evaluated at 1d,3d and 7d after the end of reperfusion,and then the brain was taken to measure the cerebral infarct volume.Immunofluorescence was used to detect the expressions of BrdU and CD31 in rats,and Western blot was used to detect the expressions of TGF-β1,Smad and VEGF.Results The cerebral ischemia/reperfusion caused neurological damage in rats in different degree.As time progressed,the neurological function of the rats in the stroke and exercise+stroke groups gradually improved.Compared with the stroke group,the cerebral infarction volume of rats in the exercise+stroke group was significantly reduced(P<0.05),and the neurological score significantly down-regulated(P<0.05).Long-term exercise significantly increased the number of BrdU-positive cells and increased the positive expression of CD31(P<0.05).At the same time,it increased the expression levels of TGF-β1,p-Smad3 and VEGF(P<0.05).In addition,compared with the exercise+stroke group,the intervention of TGF-β1 inhibitors significantly reversed the long-term exercise-mediated increase in BrdU and CD31 expression(P<0.05),and reduced the expression levels of TGF-β1,p-Smad3 and VEGF(P<0.05),which eventually leads to the inhibition of neuron and neurovascular endothelial cell proliferation(P<0.05),resulting in an increase in the neurological scores of rats(P<0.05).Conclusion Long-term exercise can up-regulate neuron and neurovascular endothelial cell regeneration through the TGF-β1/Smad3 signaling pathway,reduce the volume of cerebral infarction in the ischemic area,and exert a significant neuroprotective effect on stroke rats.

关 键 词：神经血管新生 神经元增殖 脑卒中 大鼠 长期运动 

分 类 号：R743.3[医药卫生—神经病学与精神病学]