Dexmedetomidine Attenuates Cisplatin-induced Impaired Cognitive Function Through Mmu-miR-429-3p In Rats

Background:Chemotherapy-induced cognitive impairment(CICI)is commonly reported following the administration of chemotherapeutic agents and comprises a wide variety of neurological problems.No effective treatments for CICI are currently available.Dexmedetomidine,as a recognized sedative,has antioxidant,antiinflammatory and anti-apoptosis effects.The mechanism of dexmedetomidine on cisplatin-induced CICI and mitochondrial dysfunction is still unclear.Objective:This study aimed to evaluate the protective effect of dexmedetomidine on cisplatin-induced CICI.Mi RNA sequencing was used to screen the differentially expressed mi RNAs in rats treated with dexmedetomidine.To explore the mechanism of dexmedetomidine mediating mmu-mir-429-3p in alleviating cisplatin induced hippocampal neuron injury.Methods:Eighteen male Sprague–Dawley rats(200-250 g)were randomly divided into three groups: health control group,model group of rats that were injected with 5mg/kg cisplatin;before 30 min,treatment group of rats that were injected with 30?g/kg dexmedetomidine,then injected with equal cisplatin,once a week,total four weeks.The learning memory ability,survival and ultrastructure of hippocampal neurons in rats were detected by morris water maze test,Nissl staining and TEM analysis.Mi RNA sequencing was conducted to screen differentially expressed mi RNAs in this three groups of hippocampal tissues.Then we selected 5 candidate mi RNAs verified by q RT-PCR.The effects of dexmedetomidine and mmu-mir-429-3p on mt DNA damage induced by cisplatin and hippocampal neuron apoptosis were respectively detected by q RT-PCR and immunofluorescence assay.Results:The morris water maze test showed that dexmedetomidine had protective effect on injury of the learning memory ability induced by cisplatin.Nissl staining and TEM assays revealed that dexmedetomidine significantly prevented the decrease of hippocampal neurons and the injury of mitochondria induced by cisplatin.Mi RNA sequencing results showed differential expression of 39 mi RNAs after dexmedeto-midine treatment,then q RT-PCR results showed significant differential expression of mmu-mir-429-3p in five candidate mi RNAs.Finally,q RT-PCR and immunofluor-escence assay showed that dexmedetomidine and mmu-mir-429-3p attenuates mt DNA damage and hippocampal neuron apoptosis induced by cisplatin.Conclusion:Dexmedetomidine alleviates cisplatin-induced cognitive impairment and mitochondrial dysfunction in rats through mmu-mir-429-3p.