Dexmedetomidine‐up‐regulated microRNA‐381 exerts anti‐inflammatory effects in rats with cerebral ischaemic injury via the transcriptional factor IRF4
| Autor: | Jian-Yong Yan, Hua Fang, Jian-Ping Zhang, Hua-Feng Li, Miao Yang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine neuron cell apoptosis Hippocampus Apoptosis Inflammation Pharmacology Brain Ischemia 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation IRF4 In vivo medicine Animals microRNA‐381 Neurons TUNEL assay cerebral ischaemic injury business.industry Gene Expression Profiling Pyramidal Cells Interleukin-9 dexmedetomidine Interleukin Original Articles Cell Biology IL‐9 Rats Oxygen Disease Models Animal MicroRNAs Glucose 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation nervous system 030220 oncology & carcinogenesis Interferon Regulatory Factors Molecular Medicine Original Article RNA Interference Neuron medicine.symptom business Signal Transduction |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 1582-1838 |
| DOI: | 10.1111/jcmm.16153 |
| Popis: | Dexmedetomidine (Dex) possesses analgesic and anaesthetic values and reported being used in cerebral ischaemic injury therapeutics. Accumulating studies have determined the effect of microRNAs (miRNAs) on the cerebral ischaemic injury. Thus, the present study aimed to unravel the molecular mechanism of miR‐381 and Dex in cerebral ischaemic injury. For this purpose, the cerebral ischaemic injury rat model was established by induction of middle cerebral artery occlusion (MCAO) and expression of miR‐381 and IRF4 was determined. Thereafter, MCAO rats were treated with Dex, miR‐381 mimic, miR‐381 inhibitor and oe‐IRF4 respectively, followed by evaluation of neurological function. Furthermore, neuron cells were isolated from the hippocampus of rats and subjected to oxygen‐glucose deprivation (OGD). Then, OGD‐treated neuron cells and primary neuron cells were examined by gain‐ and loss‐of‐function assay. Neuron cell apoptosis was detected using TUNEL staining and flow cytometry. The correlation between interferon regulatory factor 4 (IRF4) and interleukin (IL)‐9 was detected. Our results showed down‐regulated miR‐38 and up‐regulated IRF4 in MCAO rats. Besides, IRF4 was targeted by miR‐381 in neuron cells. Dex and overexpressed miR‐381, or silenced IRF4 improved the neurological function and inhibited neuron cell apoptosis in MCAO rats. Additionally, in MCAO rats, Dex was found to increase the miR‐381 expression and reduced IRF4 expression to decrease the IL‐9 expression, which suppressed the inflammatory response and cell apoptosis both in vivo and in vitro. Importantly, our study demonstrated that Dex elevated the expression of miR‐381, which ultimately results in the inhibition of inflammation response in rats with cerebral ischaemic injury. |
| Databáze: | OpenAIRE |
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