title: Neuroprotective Effect of Simvastatin via Inducing the Autophagy on Spinal Cord Injury in the Rat Model.
abstract: Simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, is invariably used to treat cardiovascular diseases. Simvastatin has been recently demonstrated to have a neuroprotective effect in nervous system diseases. The present study aimed to further verify the neuroprotection and molecular mechanism of simvastatin on rats after spinal cord injury (SCI). The expression of Beclin-1 and LC3-B was evidently enhanced at postoperation days 3 and 5, respectively. However, the reduction of the mTOR protein and ribosomal protein S6 kinase p70 subtype (p70S6K) phosphorylation level occurred at the same time after SCI. Simvastatin significantly increased the expression of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF). Meanwhile, immunofluorescence results indicated that the expression of chondroitin sulfate proteoglycan (CSPG) and caspase-3 protein was obviously reduced by simvastatin. Furthermore, Nissl staining and Basso, Beattie, and Bresnahan (BBB) scores showed that the quantity and function of motor neurons were visibly preserved by simvastatin after SCI. The findings of this study showed that simvastatin induced autophagy by inhibiting the mTOR signaling pathway and contributed to neuroprotection after SCI.
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Liaoning Medical University, Jinzhou 121000, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Gao
authors.affiliation: College of Pharmacy, Liaoning Medical University, Jinzhou 121000, China.
authors.forename: Guannan
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Liaoning Medical University, Jinzhou 121000, China.
authors.forename: Yansong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurobiology and Key Laboratory of Neurodegenerative Diseases of Liaoning Province, Liaoning Medical University, Jinzhou 121000, China.
authors.forename: Donghe
authors.initials: D
authors.lastname: Han
authors.affiliation: Department of Neurobiology and Key Laboratory of Neurodegenerative Diseases of Liaoning Province, Liaoning Medical University, Jinzhou 121000, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Bi
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Liaoning Medical University, Jinzhou 121000, China.
authors.forename: Yajiang
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Liaoning Medical University, Jinzhou 121000, China.
authors.forename: Tianchen
authors.initials: T
authors.lastname: Yao
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Liaoning Medical University, Jinzhou 121000, China.
authors.forename: Zhanghui
authors.initials: Z
authors.lastname: Wan
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Liaoning Medical University, Jinzhou 121000, China.
authors.forename: Haihong
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Liaoning Medical University, Jinzhou 121000, China.
authors.forename: Xifan
authors.initials: X
authors.lastname: Mei
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D001343:Autophagy / Q000187:drug effects; D000071186:Beclin-1; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D002318:Cardiovascular Diseases / Q000188:drug therapy; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000096:biosynthesis; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D051381:Rats; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D019821:Simvastatin / Q000008:administration & dosage*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000096:biosynthesis
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D019208:Brain-Derived Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008869:Microtubule-Associated Proteins; D018696:Neuroprotective Agents; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D019821:Simvastatin; D058570:TOR Serine-Threonine Kinases; C512829:Becn1 protein, rat; C526109:Anxa3 protein, rat; C546845:mTOR protein, rat