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Inhibitory effect of miRNA-126 on inflammatory response in mice with cerebral ischemia-reperfusion injury / 医学研究生学报
Journal of Medical Postgraduates ; (12): 377-383, 2020.
Article in Chinese | WPRIM | ID: wpr-821858
ABSTRACT
ObjectiveThe mechanism of cerebral ischemia-reperfusion injury is highly associated with the inflammatory response. MiRNA-126 plays a key role in vascular inflammation. This study aims to investigate the effect of miRNA-126 on the inflammatory response in mice accompanying cerebral ischemia-reperfusion injury through the NLRP3/NF-κB signal axis, and to explore the mechanisms involved.Methods A total of forty-eight male mice were randomly divided into four groups the sham-operated group, cerebral ischemia-reperfusion model group, miRNA negative control group (miRNA-126 agomir NC group) and miRNA-126 overexpression group (miRNA-126 agomir group), and each group included twelve mice. The neurobehavioral score was recorded. The left-brain of the mice was sacrificed after anesthesia, and the water content of the brain tissue was measured. HE staining and light microscopy were used to identify the histopathological changes of the cerebral of the mice. The expression levels of inflammatory cytokines IL-1β and IL-6 in brain tissue and serum of mice were detected by ELISA. Western Blot method was used to determine the protein expression levels of NLRP3, ASC, caspase-1, NF-κB p65, NF-κB P50, p-NF-κB 65 and p-NF-κB 50 in brain tissues of mice in each group. RT-PCR was used to test the expression levels of miRNA126, NLRP3, ASC, caspase-1, NF-κB p65 and NF-κB P50 in brain tissue and serum of mice.ResultsIn the sham-operated group, the morphology, and structure of cerebral cortex were normal as healthy mice, being with the dense and orderly arrangement of nerve fibers, with no occurrence of impaired nerve function, and the neurobehavioral score was zero. In both of model group and the miRNA-126 agomir NC group, the ruptured cerebral cortex could be observed visually being with necrotic and disordered cells. The blurred pyknosis and interstitial edema occurred with increased water content of brain tissue. The nerve damage was observed with a significantly increased neurobehavioral score (P<0.05). Compared to the model group, the pathological morphology of the cerebral cortex in the miRNA-126 agomir group was significantly improved, and the number of necrotic cells was decreased, the arrangement of which was denser and more orderly. Reduced interstitial edema and the neurobehavioral score were identified. The significantly improved nerve injury and the decreased water content of brain tissue were observed as well (P<0.05). Compared to the sham-operated group A, the expression level of miRNA-126 mRNA in the model group and the miRNA-126 agomir NC group decreased significantly. The expression level of IL-1β and IL-6 increased, while the expression levels of NLRP3, ASC, caspase-1, NF-κB p65, NF-κB p50, p-NF-κB p65, p-NF-κB p50, and NLRP3, ASC, caspase-1, NF-κB p65, NF-κB p50 mRNA increased generally (P<0.05). Compared to the model group and the miRNA-126 agomir NC group, the expression level of miRNA-126 mRNA in the miRNA-126 agomir group increased. However, the expression level of IL-1β and IL-6 decreased, and the expression level of NLRP3/NF-κB signal axis related gene protein and mRNA decreased (P<0.05).ConclusionOverexpression of miRNA-126 can inhibit the expression of NLRP3/NF-κB signal axis related genes and the level of inflammation in brain tissue, and improve the neurological injury of cerebral ischemia-reperfusion in mice.

Full text: Available Index: WPRIM (Western Pacific) Type of study: Prognostic study Language: Chinese Journal: Journal of Medical Postgraduates Year: 2020 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Type of study: Prognostic study Language: Chinese Journal: Journal of Medical Postgraduates Year: 2020 Type: Article