title: An Antagomir to MicroRNA-106b-5p Ameliorates Cerebral Ischemia and Reperfusion Injury in Rats Via Inhibiting Apoptosis and Oxidative Stress.
abstract: We previously observed that microRNA miR-106b-5p significantly increased in serum of patients with acute ischemic stroke. The present study was to determine whether miR-106b-5p antagomir can protect against cerebral ischemia/reperfusion (I/R) injury and elucidate its underlying mechanisms. Middle cerebral artery occlusion (MCAO) was operated on male Sprague Dawley rats. MiR-106b-5p antagomir significantly decreased neurological deficit scores, infarct volumes, and neuronal injury. Furthermore, miR-106b-5p antagomir markedly reduced malondialdehyde (MDA) content, restored superoxide dismutase (SOD) activity, increased the expression of myeloid cell leukemia-1 (Mcl-1) and B cell lymphoma-2 (Bcl-2), and decreased the expression of Bax in the ischemic cortex. In PC12 cells, miR-106b-5p inhibitor increased the Mcl-1 and Bcl-2 expression, which provided protection against glutamate-induced apoptosis and oxidative damage, as evidenced by decreased lactate dehydrogenase (LDH) release, and enhanced SOD activity. Notably, luciferase reported assay proved Mcl-1 was the target gene of miR-106b-5p. In conclusion, our data indicates that the neuroprotective effects of miR-106b-5p antagomir on cerebral I/R injury are associated with its inhibition of apoptosis and oxidative stress, suggesting a potential therapeutic target for ischemic stroke.
authors.affiliation: Department of Clinical Laboratory, Jiangsu Province Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, Jiangsu, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Li
authors.affiliation: The Second Clinical College, Nanjing University of Chinese Medicine, Nanjing, 210046, Jiangsu, China.
authors.forename: Meihong
authors.initials: M
authors.lastname: Shen
authors.affiliation: Department of Clinical Laboratory, Jiangsu Province Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, Jiangsu, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: Basic Medical Sciences, Nanjing University of Chinese Medicine, Nanjing, 210046, Jiangsu, China.
authors.forename: Jinping
authors.initials: J
authors.lastname: Wu
authors.affiliation: Basic Medical Sciences, Nanjing University of Chinese Medicine, Nanjing, 210046, Jiangsu, China.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, Jiangsu Province Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, Jiangsu, China.
authors.forename: Fengmeng
authors.initials: F
authors.lastname: Teng
authors.affiliation: Department of Clinical Laboratory, Jiangsu Province Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, Jiangsu, China. zzzzcb99@163.com.|Basic Medical Sciences, Nanjing University of Chinese Medicine, Nanjing, 210046, Jiangsu, China. zzzzcb99@163.com.
authors.forename: Chunbing
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000070416:Antagomirs / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001483:Base Sequence; D002545:Brain Ischemia / Q000150:complications* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D018698:Glutamic Acid / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000235:genetics / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000070416:Antagomirs; D000975:Antioxidants; C579093:Mcl1 protein, rat; C000621081:MicroRNA-106b-5p, rat; D035683:MicroRNAs; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D051028:bcl-2-Associated X Protein; D018698:Glutamic Acid; D008315:Malondialdehyde; D013482:Superoxide Dismutase
keywords: Apoptosis; Ischemic stroke; MiR-106b-5p; Middle cerebral artery occlusion; Oxidative stress