| ObjectiveInvestigating the effects of acute exposure to different concentrations of sodium arsenite(NaAs02)on the heart of C57BL/6 mice and the protective effect of sodium tanshinone IIA sulfonate on subchronic cardiotoxicity of sodium arsenite.MethodsC57BL/6 mice were used in vivo experiments.The experiments were divided into two parts:acute experiment and sub-chronic experiment.The mice were divided into four groups for acute experiment:the control group,the low-dose group,the middle-dose group and the high-dose group exposed to different concentration of sodium arsenite.The mice in each group were administered by intragastric administration,and the mice in control group were given normal saline.The mice in experimental group were given different dose of sodium arsenite according to the body weight of mice,the doses were 2.5?5 and 10 mg/kg,respectively.After 24 hours of exposure,the mice were weighed.Three mice were randomly selected for perfusion and tissue fixation.The other mice were sacrificed by cervical vertebra disociation and dissected.The heart was removed and the heart weight was weighed.Second-generation sequencing was used to detect differentially expressed miRNAs and mRNAs in the control and middle-dose groups,and bioinformatics analysis was performed on the sequencing results.The pathological changes of the fixed heart tissues were detected by hematoxylin-eosin staining(HE staining),and the mRNA expression levels of TNF-?,CD11b,IL1R2 and TIMP2 were detected by real-time fluorescent quantitative PCR.The second part is a sub-chronic experiment.The experiment is divided into 4 groups:control group,sodium arsenite group,sodium tanshinone ?A sulfonate group,sodium arsenite and tanshinone ?A sulfonate group,12 rats in each group.Sodium arsenite was administered by free drinking water at a concentration of 50 mg/L,and sodium tanshinone ?A sulfonate was administered at a dose of 5 mg/kg.After sodium arsenate was applied for 16 days,the drug was administered until the end of the experiment;after the end of the drug,75 days in total,the body weight of the mice was weighed and electrocardiogram was detected.Three mice were randomly selected for perfusion and tissue fixation.The remaining mice were sacrificed by cervical vertebra disociation and dissected.The heart was removed,the weight of the heart was weighed,and the whole blood reduced glutathione activity was measured.HE staining for myocardial histopathology.ResultsThe first part of the acute experiment shows that there was no significant difference in the mental state and hair color of the rats.The results of the study showed that there was no significant difference in body weight,heart weight and cardiac organ coefficient between the groups(P>0.05).The second-generation sequencing results of sodium arsenite medium dose group and control group revealed that there were 33 differentially expressed miRNAs such as miR-148a-3p?miR-451a and miR-206-3p and 4744 differentially expressed mRNAs,among which genes the 2644 mRNA expressions were raised,1830 genes were down-regulated.The GO analysis results of bioinformatics show that there are 20 GO term in the biological,molecular function and cellular components of the candidate target gene enrichment.The KEGG analysis of bioinformatics found that target genes were enriched in 144 biosignal pathways(pathway term)such as chronic myeloid leukemia,MAPK signaling pathway and chronic myeloid leukemia.The results of HE staining showed that the cardiomyocytes in the control group were closely arranged,the cytoplasm was rich,there was no inflammatory cell infiltration,and there was no necrosis.There was no significant change in the low-dose group compared with the control group,and the myocardial cells were arranged closely.Compared with the control group,the middle-dose group had less dense myocardial fibers and irregular arrangement,showing scattered inflammatory cell infiltration.Compared with the control group,some of the nucleus disappeared,the eosinophilicity of the cytoplasm increased,the cell membrane was incomplete,and the inflammatory cells infiltrated by neutrophils were partially infiltrated.Real-time PCR results showed that the TNF-a content in the low dose group was higher than that in the control group,The content of TNF-a in the middle dose group was higher than that in the control group,and the difference was statistically significant(P<0.05).There was no significant difference in the content of TNF-? between high dose and control group(P>0.05).The content of high-dose CD11b was higher than that of the control group,and the difference was statistically significant(P<0.05).There was no significant difference in the IL1R2 between the groups(P>0.05),There was no significant difference in TIMP2 between the groups(P>0.05).The second part of the sub-chronic experiment showed that through the observation of the mice,the mice in the sodium arsenite group were inferior to other mice,and the hair color of the mice was worse than that of the other groups.The weight of the mice in sodium arsenite group was lower than that of the normal group,and the difference was statistically significant(P<0.05).However,there was no significant difference in heart weight and organ coefficient(P>0.05).The data showed that sodium arsenite and sodium tanshinone ?A sulfonate group had a slight increase in body weight of arsenate,but the difference was not statistically significant(P>0.05);Sodium arsenite and tanshinone ?A sulfonate group had a slight increase in cardiac organ coefficient,but the difference was not statistically significant(P>0.05).The results of electrocardiogram showed that the data of arsenite group and normal group were compared:heart rate decreased,but the difference was not statistically significant(P>0.05),there was no significant difference in T wave amplitude(P>0.05),QT interval prolonged.The difference was statistically significant(P<0.05);sodium arsenite and tanshinone ?A sulfonate group compared with sodium arsenite group heart rate increased but the difference was not statistically significant(P>0.05),T wave amplitude difference was not Statistical significance(P>0.05),QT interval shortened,the difference was statistically significant(P<0.05)The content of GSH in the sodium arsenite group was lower than that in the normal group,the difference was statistically significant(P<0.05).The reduced GSH content of the sodium arsenite group was lower than that of the normal group,and the difference was statistically significant(P<0.05).Compared with the mice in sodium arsenite group,the mice in sodium arsenite plus sodium tanshinone ?A sulfonate group had increased GSH content,the difference was statistically significant(P<0.05);The HE results of the subchronic experiment showed that the myocardial cells in the control group had normal morphology,long spindle shape,complete cell membrane and nuclear structure,moderate ventricular size,normal wall thickness,uniform tissue staining,and neatly arranged;There was no abnormality in the cardiomyocytes of the sodium tanshinone IIA sulfonate group.The morphology of the myocardial cells was almost normal,and the cell nucleus and cell membrane structure were almost intact,and the tissue staining was uniform;Inflammatory cell infiltration and myocardial fiber breakage were observed in the sodium arsenite group;A single sporadic inflammatory cell infiltration was observed in the sodium arsenite and tanshinone ?A sulfonate group,but significantly less than the sodium arsenite group,and no myocardial fiber rupture was observed.ConclusionsSodium arsenite can induce oxidative stress and inflammation in the heart,lead to differential expression of miRNA and mRNA in cardiac tissue,caused the QT interval of the electrocardiogram in mice to prolong,it shows that sodium arsenite causes heart damage in mice to some extent.Sodium tanshinone ?A sulfonate has protective effects on oxidative stress,Inflammatory reaction and electrocardiogram changes induced by sodium arsenite,and reduce the extension of the heart QT interval in mice. |
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