Effects And Mechanisms Of Metformin On Inflammation After Spinal Cord Injury Via Wnt/β-catenin Signaling Pathway

Objective: To verify the regulation mechanism of metformin on inflammatory response and nerve function after spinal cord injury(SCI)through Wnt/β-catenin signaling pathway.Background: Spinal cord injury(SCI)is a clinically common and severely disabling traumatic disease of the central nervous system.The incidence is about 10.5 per 100,000.There are more than 200,000 new cases worldwide each year,and there is an upward trend.Because SCI often leads to severe dysfunction of the limbs below the injured segment,so in addition to affecting the quality of life and physical and mental health of patients,it will also cause a very large financial burden to the family and society,but the current clinical treatment effect is not satisfactory.Studies have shown that the Wnt/β-catenin signaling pathway plays an important role in SCI,and metformin has been reported to play a neuroprotective effect in the central nervous system.But whether metformin improves spinal cord injury through Wnt/β-catenin signaling is unclear.Therefore,this study intends to verify whether metformin can improve spinal cord injury through the Wnt/β-catenin signaling pathway through the following content.Methods: Rats were divided into the sham group,SCI group,SCI +metformin group,metformin + XAV939 group(XAV939 is an effective inhibitor of the Wnt/β-catenin signaling pathway),and methylprednisolone group.BBB scores were used to detect motor function recovery at different time points(0,1,3,7,14,21,and 28 days)in SCI rats.Western blot was used to detect the expression changes ofβ-catenin,NF-κB,TNF-α,Caspase-3,and BDNF in different groups of SCI.The expression changes of β-catenin and NF-κB in spinal cord tissues of each group were detected by immunofluorescence.The apoptosis of spinal cord neurons was detected by TUNEL staining.The pathological characteristics of spinal cord tissue and the number of spinal cord neurons were observed by HE and Nissl staining.Results: Metformin(50 mg/kg)promoted motor functional recovery in rats after SCI,increased the expressions of β-catenin and brain derived neurotrophic factor(BDNF),inhibited neuron apoptosis and inflammatory response,and improved the recovery of pathological morphology at the injury site by activating the Wnt/β-catenin signaling pathway.Conclusion: We found a possible mechanism that metformin could reduce inflammation and apoptosis,and promote functional recovery of SCI rats through activating Wnt/β-catenin signaling pathway.