松油烯-4-醇通过调控SIRT1/FOXO1信号通路对慢性肾病小鼠肾小管上皮-间质转化的影响OA

Aim:To investigate the effect of terpinen-4-ol on renal tubular epithelial-mesenchymal transition(EMT)in mice with chronic kidney disease(CKD)by regulating the sirtuin 1(SIRT1)/forkhead box O1(FOXO1)signaling pathway.Methods:A total of 24 mice were randomly divided into 4 groups:normal control group,CKD model group,and low and high dose terpinen-4-ol groups,with 6 mice in each group.Except the normal control group,CKD models were established in the other 3 groups.After successful modeling,the normal control group and CKD model group were given equal volumes of olive oil by gavage;low and high dose terpinen-4-ol groups were administered 10 and 20 mg/kg terpinen-4-ol by gavage,respectively,once a day for 6 consecutive weeks.After the experiment,blood samples were collected via retro-orbital puncture and serum BUN and Scr levels were measured;after euthanizing,kidney tissue was taken and observed for pathological changes using HE and Masson staining.Western blot was used to detect the expression levels of E-cadherin,α-SMA,Vimentin,SIRT1,and FOXO1 proteins.Another 36 mice were divided into 6 groups:Lv-NC group,Lv-NC+CKD group,Lv-NC+CKD+terpinen-4-ol group,Lv-Sirt1 RNAi group,Lv-Sirt1 RNAi+CKD group,Lv-Sirt1 RNAi+CKD+terpinen-4-ol group,with 6 mice in each group.The establishment of CKD model and the administration method of terpinen-4-ol(20 mg/kg)were the same as above.Lv-NC group,Lv-NC+CKD group,Lv-NC+CKD+terpinen-4-ol group were administered Lv-NC(5×107 U/mouse)via tail vein injection,while the other3 groups were injected Lv-Sirt1 RNAi(5×107 U/mouse)for2 consecutive weeks.After euth-anizing,kidney tissue was taken and Western blot was used to detect the expression levels of E-cadherin,α-SMA,Vimentin,SIRT1,and FOXO1 proteins.HE and Masson staining were used to observe the pathological changes in kidney tissue.Re-sults:Terpinen-4-ol could improve renal function damage in CKD mice,downregulate the expression levels of α-SMA and Vimentin proteins in renal tissue,and upregulate the expression levels of E-cadherin,SIRT1,and FOXO1 proteins(P<0.05).Knocking down Sirt1 expression can exacerbate kidney damage in CKD mice,further upregulate the expression levels of α-SMA and Vimentin proteins,downregulate the expression levels of E-cadherin,SIRT1,and FOXO1 proteins(P<0.05),while terpinen-4-ol could reverse this phenomenon(P<0.05).Conclusion:Terpinen-4-ol may affect EMT by acti-vating the SIRT1/FOXO1 signaling pathway,thereby improving kidney injury in CKD mice.