title: Salvianolic acid A ameliorates the integrity of blood-spinal cord barrier via miR-101/Cul3/Nrf2/HO-1 signaling pathway.
abstract: Salvianolic acid A (Sal A), a bioactive compound isolated from the Chinese medicinal herb Danshen, is used for the prevention and treatment of cardiovascular diseases. However, the protective function of Sal A on preserving the role of blood-spinal cord barrier (BSCB) after spinal cord injury (SCI) is unclear. The present study investigated the effects and mechanisms of Sal A (2.5, 5, 10mg/kg, i.p.) on BSCB permeability at different time-points after compressive SCI in rats. Compared to the SCI group, treatment with Sal A decreased the content of the Evans blue in the spinal cord tissue at 24h post-SCI. The expression levels of tight junction proteins and HO-1 were remarkably increased, and that of p-caveolin-1 protein was greatly decreased after SCI Sal A. The effect of Sal A on the expression level of ZO-1, occluding, and p-caveolin-1 after SCI was blocked by the HO-1 inhibitor, zinc protoporphyrin IX (ZnPP). Also, Sal A inhibited the level of apoptosis-related proteins and improved the motor function until 21days after SCI. In addition, Sal A significantly increased the expression of microRNA-101 (miR-101) in the RBMECs under hypoxia. AntagomiR-101 markedly increased the RBMECs permeability and the expression of the Cul3 protein by targeting with 3'-UTR of its mRNA. The expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and HO-1 was significantly increased after agomiR-101 treatment. Therefore, Sal A could improve the recovery of neurological function after SCI, which could be correlated with the repair of BSCB integrity by the miR-101/Cul3/Nrf2/HO-1 signaling pathway.
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital, Jinzhou Medical University, People Street No. 2-5, GuTa District, Jinzhou 121001, Liaoning Province, PR China.
authors.forename: De-Shui
authors.initials: DS
authors.lastname: Yu
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital, Jinzhou Medical University, People Street No. 2-5, GuTa District, Jinzhou 121001, Liaoning Province, PR China.
authors.forename: Yan-Song
authors.initials: YS
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital, Jinzhou Medical University, People Street No. 2-5, GuTa District, Jinzhou 121001, Liaoning Province, PR China.
authors.forename: Yun-Long
authors.initials: YL
authors.lastname: Bi
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital, Jinzhou Medical University, People Street No. 2-5, GuTa District, Jinzhou 121001, Liaoning Province, PR China.
authors.forename: Zhan-Peng
authors.initials: ZP
authors.lastname: Guo
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital, Jinzhou Medical University, People Street No. 2-5, GuTa District, Jinzhou 121001, Liaoning Province, PR China.
authors.forename: Ya-Jiang
authors.initials: YJ
authors.lastname: Yuan
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital, Jinzhou Medical University, People Street No. 2-5, GuTa District, Jinzhou 121001, Liaoning Province, PR China.
authors.forename: Song-Ming
authors.initials: SM
authors.lastname: Tong
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital, Jinzhou Medical University, People Street No. 2-5, GuTa District, Jinzhou 121001, Liaoning Province, PR China.
authors.forename: Rui-Chao
authors.initials: RC
authors.lastname: Su
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital, Jinzhou Medical University, People Street No. 2-5, GuTa District, Jinzhou 121001, Liaoning Province, PR China.
authors.forename: Li-Hao
authors.initials: LH
authors.lastname: Ge
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital, Jinzhou Medical University, People Street No. 2-5, GuTa District, Jinzhou 121001, Liaoning Province, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Physiology, Life Science and Biopharmaceutical Institution, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning Province, PR China.
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Pan
authors.affiliation: Department of Physiology, Life Science and Biopharmaceutical Institution, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning Province, PR China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Guan
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital, Jinzhou Medical University, People Street No. 2-5, GuTa District, Jinzhou 121001, Liaoning Province, PR China. Electronic address: Cyang_2016@126.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
mesh_terms: D000818:Animals; D002109:Caffeic Acids / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects* / Q000502:physiology; D002317:Cardiovascular Agents / Q000494:pharmacology*; D051242:Caveolin 1 / Q000378:metabolism; D044842:Cullin Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D000860:Hypoxia / Q000188:drug therapy / Q000378:metabolism; D007773:Lactates / Q000494:pharmacology*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D002109:Caffeic Acids; D002317:Cardiovascular Agents; C495537:Cav1 protein, rat; D051242:Caveolin 1; C561111:Cul3 protein, rat; D044842:Cullin Proteins; D007773:Lactates; C579142:MIRN101 microRNA, rat; D035683:MicroRNAs; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; C495637:Nfe2l2 protein, rat; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; C066201:salvianolic acid A; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat
keywords: Blood-spinal cord barrier; Heme oxygenase-1; Salvianolic acid A; Spinal cord injury; Tight junction