中国组织工程研究2024，Vol.28Issue(31)：5036-5041,6.DOI:10.12307/2024.709
颅内移植人骨髓间充质干细胞减轻大鼠脑缺血再灌注损伤
Intracranial transplantation of human bone marrow mesenchymal stem cells alleviates rat brain ischemia-reperfusion injury
摘要
Abstract
BACKGROUND:Studies have found that activation of nuclear factor-erythroid 2-related factor 2/heme oxidase-1(Nrf2/HO-1)pathway can alleviate oxidative stress caused by cerebral ischemia-reperfusion injury,but whether human bone marrow mesenchymal stem cells(hBMSC)can activate Nrf2/HO-1 pathway to alleviate cerebral ischemia-reperfusion injury is still lacking relevant studies. OBJECTIVE:To investigate whether intracranial transplantation of hBMSC alleviates oxidative stress injury in cerebral ischemia-reperfusion animal models by activating Nrf2/HO-1 pathway. METHODS:Totally 40 male SPF SD rats were randomly divided into sham operation group,model group,hBMSC transplantation group,hBMSC+solvent group and hBMSC+Nrf2 inhibitor group.Each group consisted of eight animals.In the model group and the hBMSC transplantation group,middle cerebral artery occlusion model was prepared by thread embolization method.The thread embolization was removed 1 hour later,and 30 μL PBS or hBMSC cultured to at least passage 5 was injected into the right cortex and striatum of rats.In the hBMSC+Nrf2 inhibitor group and hBMSC+solvent group,the left ventricle was injected with Nrf2 inhibitor Brusatol and its solvent dimethyl sulfoxide respectively 24 hours before model establishment,then the middle cerebral artery occlusion model was prepared,and hBMSC was injected.Relevant indexes were detected 3 days after transplantation. RESULTS AND CONCLUSION:(1)CT and TTC staining showed the same area and volume of cerebral infarction:model group>hBMSC+Nrf2 inhibitor group>hBMSC+solvent group>hBMSC transplantation group>sham operation group.(2)Hematoxylin-eosin staining and Nissl's staining showed that the ischemic brain tissue was intact and the neurons were normal in the sham operation group.Compared with the model group,the pathological morphology and neuronal injury of the hBMSC transplantation group and the hBMSC+solvent group were significantly improved.Compared with the hBMSC+solvent group,the hBMSC+Nrf2 inhibitor group had more serious pathological morphology and neuronal damage.(3)Western blot assay and oxidative stress index detection results showed that compared with the sham operation group,Nrf2 and HO-1 proteins were decreased(all P<0.05),malondialdehyde was increased and superoxide dismutase was decreased(all P<0.05)in the model group.Compared with the model group,the expression levels of Nrf2 and HO-1 proteins were increased(all P<0.05),malondialdehyde was decreased and superoxide dismutase was increased(all P<0.05)in the hBMSC transplantation group and the hBMSC+solvent group.Compared with the hBMSC+solvent group,the expression levels of Nrf2 and HO-1 proteins were simultaneously decreased(all P<0.05),and malondialdehyde was increased and superoxide dismutase was decreased(all P<0.05)in the hBMSC+Nrf2 inhibitor group.(4)These results indicate that hBMSC can alleviate cerebral ischemia-reperfusion injury possibly by activating Nrf2/HO-1 pathway.关键词
人骨髓间充质干细胞/脑缺血再灌注损伤/氧化应激/核因子E2相关因子2/血红素加氧化酶1Key words
human bone marrow mesenchymal stem cell/cerebral ischemia-reperfusion injury/oxidative stress/nuclear factor-erythroid 2-related factor 2/heme oxidase-1分类
医药卫生引用本文复制引用
宋文学,徐卡娅,廖益东,明江,何龙才,陈光唐,陈晨,王梓力,熊明松,崔君拴..颅内移植人骨髓间充质干细胞减轻大鼠脑缺血再灌注损伤[J].中国组织工程研究,2024,28(31):5036-5041,6.基金项目
国家自然科学基金项目(81901173,82060231),项目负责人:徐卡娅 （81901173,82060231）
贵州医科大学附属医院博士科研启动基金项目(gyfybsky-2021-6),项目负责人:徐卡娅 （gyfybsky-2021-6）
2022年国家自然科学基金培育项目计划(gyfynsfc-2022-08),项目负责人:徐卡娅 （gyfynsfc-2022-08）
贵州省科技计划项目(ZK[2023]重点039),项目负责人:徐卡娅National Natural Science Foundation of China,Nos.81901173 and 82060231(to XKY) （ZK[2023]重点039）
Doctoral Research Start-up Fund Project of Affiliated Hospital of Guizhou Medical University,No.gyfybsky-2021-6(to XKY) （to XKY）
Cultivation Project Plan of National Natural Science Foundation of China in 2022,No.gyfynsfc-2022-08(to XKY) （to XKY）
Science and Technology Plan Project of Guizhou Province,No.ZK[2023]Key 039(to XKY) （to XKY）
