miR-16-5p通过调控Hippo/YAP通路对脑出血大鼠神经元凋亡的影响  

Influences of miR-16-5 p on neuronal apoptosis in rats with intracerebral hemorrhage by regulating Hippo/YAP pathway

作　　者：赵胜 杨华[1,3] 吴钊 蒋鸫 ZHAO Sheng;YANG Hua;WU Zhao;JIANG Dong(Clinical College of Guizhou Medical University,Guiyang 550001,China;Guizhou Medical University Affiliated Jinyang Hospital,Guiyang 550001,China;Neurosurgery Department of Guizhou Medical University Affiliated Hospital,Guiyang 550001,China)

机构地区：[1]贵州医科大学临床学院,贵阳550001 [2]贵州医科大学附属医院金阳医院,贵阳550001 [3]贵州医科大学附属医院神经外科,贵阳550001

出　　处：《中国免疫学杂志》2025年第2期336-341,350,共7页Chinese Journal of Immunology

摘　　要：目的:探讨miR-16-5p通过调控Hippo/Yes相关蛋白(YAP)通路对脑出血(ICH)大鼠神经元凋亡的影响。方法:大鼠随机分为正常对照(NC)组、ICH模型(Model)组、antagomir阴性对照(antagomir NC)组、miR-16-5p antagomir组、miR-16-5p antagomir+葫芦素B(Hippo通路激活剂)组、miR-16-5p antagomir+维替泊芬(YAP抑制剂)组,每组18只。除NC组外,其他组大鼠均向右侧纹状体中注入胶原酶Ⅶ构建ICH模型,处理结束后检测神经功能评分;qRT-PCR检测miR-16-5p表达,干-湿重法检测脑组织含水量,HE染色检测血肿周围脑组织病理变化,试剂盒检测氧化应激指标超氧化物歧化酶(SOD)、丙二醛(MDA)及炎症因子IL-6、TNF-α水平,TUNEL法检测神经细胞凋亡,Western blot检测Bim、Bcl2相关X蛋白(Bax)、YAP1、磷酸化c-Jun氨基末端激酶(p-JNK)蛋白表达。结果:与NC组比较,Model组大鼠血肿周围脑组织病理损伤严重,神经功能评分、miR-16-5p表达、脑组织含水量、MDA、IL-6、TNF-α水平、神经细胞凋亡率、Bim、Bax、p-JNK蛋白表达升高,SOD水平、YAP1蛋白表达降低;miR-16-5p antagomir对ICH大鼠以上变化均有显著改善作用;葫芦素B和维替泊芬均能减弱miR-16-5p antagomir对ICH大鼠的脑保护作用。结论:下调miR-16-5p减轻ICH大鼠脑损伤的保护作用可能与抑制Hippo通路、激活YAP有关。Objective:To investigate influences of miR-16-5p on neuronal apoptosis in rats with intracerebral hemorrhage(ICH)by regulating Hippo/Yes-associated protein(YAP)pathway.Methods:Rats were randomly separated into normal control(NC)group,ICH model(Model)group,antogamir negative control(antogamir NC)group,miR-16-5p antagomir group,miR-16-5p antagomir+cucurbitacin B(Hippo pathway activator)group,miR-16-5p antagomir+verteporfin(YAP inhibitor)group,with 18 per group.Except for NC group,rats in other groups were injected with collagenaseⅦinto right caudate nucleus to construct ICH model,and neurological function scores were detected after treatment;qRT-PCR was performed to detect miR-16-5p expression;dry-wet weight method was performed to measure water content of brain tissue;HE staining was used to detect pathological changes of brain tissue around hematoma;kits was used to measure levels of oxidative stress indicators superoxide dismutase(SOD),malondialdehyde(MDA),inflammatory factors IL-6 and TNF-α;TUNEL method was performed to measure nerve cell apoptosis;Western blot was performed to measure Bim,Bcl2-associated X protein(Bax),YAP1,phosphorylated c-Jun amino-terminal kinase(p-JNK)protein expressions.Results:Compared with NC group,Model group exhibited severe brain tissue damage around hematoma,increased neurological function score,miR-16-5p expression,brain tissue water content,MDA,IL-6 and TNF-αlevels,neuronal apoptosis rate,protein expressions of Bim,Bax and p-JNK were increased,SOD level and YAP1 protein expression were decreased.miR-16-5p antagomir had significant improvement effects on above changes in ICH rats.Both cucurbitacin B and verteporfin weakened brain protective effect of miR-16-5p antagomir on ICH rats.Conclusion:Protective effect of down-regulation of miR-16-5p in ICH rats may be related to inhibition of Hippo pathway and YAP activation.

关 键 词：脑出血 miR-16-5p Hippo/Yes相关蛋白通路 神经元 凋亡 

分 类 号：R743.34[医药卫生—神经病学与精神病学]