MiRNA-135b-5p Regulates GSK3β-TLR3 Signal Pathway to Inhibit Inflammatory Response with Cerebral Ischemia-Reperfusion Injury in Mice

Abstract

Objective: The mechanism of cerebral ischemia-reperfusion injury is closely related to inflammation, and miRNA-135b-5p may play a key role in the inflammation of cerebral ischemia injury. In this study we investigate the effect of miRNA-135b-5p through GSK3 β-TLR3 signal axis on inflammatory response in mice with cerebral ischemia-reperfusion injury. Methods: 48 mice were randomly divided into sham operation group (n = 12), model group (n = 12), negative control group (n = 12) and overexpression group (n = 12). After neurobehavioral score, the left brain of mice was killed and the water content of brain tissue was measured, the expression levels of TNF- α and IL-6 in brain tissue and serum were detected by ELISA method, the expression levels of TLR3, GSK3β and ERK protein in brain tissue were detected by Western Blot, and the mRNA expression levels of TLR3, GSK3 β and ERK in each group were detected by RT-PCR. Results: The neurobehavioral scores in the model group, negative control group and overexpression group were significantly higher than those in the sham operation group (P < 0.05), and the neurobehavioral scores in the overexpression group were significantly lower than those in the negative control group and model group (P < 0.05). The expression level of miRNA-135b-5p in brain tissue of mice in model group and negative control group was significantly lower than that in sham operation group, while the expression level of miRNA-135b-5p in overexpression group was significantly higher than that in other three groups. The expression levels of TNF- α and IL-6 in brain tissue and serum of mice in model group and negative control group were significantly higher than those in sham operation group, while the expression levels of TNF- α and IL-6 in overexpression group were significantly lower than those in model group and negative control group. The mRNA expression levels of TLR3, GSK3 β and ERK in the model group and negative control group were significantly higher than those in the sham operation group, while the mRNA expression levels of TLR3, GSK3 β and ERK in the overexpression group were significantly lower than those in the model group and negative control group. Conclusion: Overexpression of miRNA-135b-5p could inhibit the expression of GSK3β-TLR3 signal axis related genes and reduce the inflammatory response during cerebral ischemia-reperfusion injury, which may be a new strategy for the treatment of cerebral ischemia-reperfusion injury.