Effect And Mechanism Of Yisui Moxibustion On The Regulation Of Insulin Signaling Pathway In Hippocampal Klotho Of D-Galactose Senescent Mice

Objective:To explore the Effect of Yisui moxbustion on Klotho,insulin receptor substrate(IRS),protein kinase(AKT),forkhead box O3(FOXO3a)mRNA and protein exppressions of the hippocampal tissue in mice model with aging and provide experiment evidence for clinic application.Methods: Sixty male KM mice are randomly divided into normal group,model group,Zusanli group,Baihui group and nonacupoint group,while 14 mice in each group.Subcutaneous injection of D-galactosewas conducted in the mice in the model group and each intervention group forestabinsing aging model,and injection normal sodium with the same dosage was donducted in the normal group.At the13 th day of modeling,moxibustion at corresponding acupoints was performed in the three intervention group,seartch with the same degree was performed in the normal group and model group.Behavior test usaing morris water maze was conducted in 5 group before and after modeling.After the treatment finished,the exprresion levels of Klotho,IRS,Akt and FOXO3 a mRNAs and proteins were detected in the hippocampal tissue of the mice.Results:(1)The latent periods of the model group and nonacupoint group were longer than that of the normal group,Zusanli group or Baihui group(P < 0.05).(2)In the model group,the expression levels of Klotho and IRS mRNAs decreased,the expression levels of Akt and FOXO3 a mRNAs increased(P < 0.05)compared to the normal group(P < 0.05).Compared to the model group the expression levels of Klotho and IRS mRNAs increased but the expression levels of Akt and FOXO3 a mRNAs decreased(P < 0.05)in Zusanli group or Baihui group(P < 0.05),and no significant changes were observed in the nonacupoint group(P < 0.05).(3)In the model group,the expression levels of Klotho,p-irs-1,Akt and FOXO3 a protein decreased,the expression levels of IRS-1,p-Akt and FOXO3 a proteins decreased(P < 0.05)in Zusanli group or Baihui group(P <0.05).Conclusion(s): Anti-aging effect of Yisui moxibusition obtains on brainprobaly related to:(1)Yisui moxibusitioncanprobaly upregulate the Klotho and IRS-1 mRNA levels to promote the expression of Klotho protein in hippocampus of mice,and then stimulating the activation of IRS-1 serine inhibition site.(2)It also probably down regulate of its downstream Akt activity and thus downregulate of phosphorylation expression of its substrate FOXO3 a.