Effect Of Artemisinin On Trimethyltin Chloride-induced Hippocampal Damage In Mic

Research objectives: The aim of this study was to investigate whether ARS could alleviate TMT-induced neurotoxicity and whether PK2/PKRs-related signaling pathways play a role in it.Research methods: Sixty male Balb/c mice were divided into Con group,TMT group,TMT+ARS group and ARS group.Mice in the TMT group received a one-time injection of TMT,while those in the drug group received intraperitoneal injection of ARS for 4 weeks.The expression of PK2-related proteins in mouse hippocampus were evaluated by immunohistochemistry.Prediction of the potential mechanism of ARS in the treatment of TMT induced nerve injury by network pharmacology.Behavioral scores were used to evaluate the neural behavior of mice.HE,Nissl and electron microscopy were used to evaluate the pathological injury of hippocampus.The expressions of PSD95,SYN1,Synaptophysin,NF-κB p65,TNF-α,PK2,PKR1 and PKR2 were detected by Western Blotting.Research results: Immunohistochemical results showed that PK2 and PKR2 protein expression were elevated in the hippocampal CA2 and CA3 regions of mice in the TMT group compared with the Con group,and PKR1 protein was not significantly altered.Network pharmacology results indicated that PK2 could interact with ARS,central nerve injury and the intersectional targets of TMT.Behavioral scores showed that seizure scores and intoxication symptoms were significantly higher in mice in the TMT group compared with the Con group,while the behavioral scores were significantly lower after ARS administration.HE and Nissl staining results showed eosinophilic cytoplasm,deep staining of nuclei and nuclear lysis in the neurons of CA3 and DG regions of the hippocampus in the TMT group compared to the Con group,and the extent of hippocampal neuronal damage was reduced in the TMT+ARS group compared to the TMT group.The electron microscopic results showed that the mitochondria of hippocampal neurons in the TMT group showed swollen vacuoles and degranulation of the rough endoplasmic reticulum compared with those in the Con group,and these phenomena were significantly reversed after administration of ARS.Western Blotting results showed that PSD95,SYN1 and Synaptophysin protein expression was significantly lower,TNF-α,NF-κB p65,PK2 and PKR2 protein expression was significantly higher in the TMT group compared to the Con group,while PKR1 protein expression was not significantly altered,compared with the TMT group,the protein expressions of PSD95,SYN1 and Synaptophysin in the TMT+ARS group were significantly increased,and the protein expressions of TNF-α,NF-κB p65,PK2 and PKR2 were significantly decreased,while the protein of PKR1 was not significantly changed.Research conclusions: TMT increased the expression of PK2 and PKR2 proteins in CA2 and CA3 regions of the hippocampus.ARS improved the ultrastructural abnormalities of hippocampus induced by TMT and alleviated the damage of hippocampal neurons.ARS alleviated nerve damage caused by TMT by regulating NF-κB-PK2 / Pk Rs-related inflammatory pathways.