Effects Of Short-Term High Salt Diet On Renal Fibrosis In C57BL/6J Mice Of Different Ages And Genders

Objective:To explore the effect of short-term high salt diet on renal fibrosis in C57BL/6 J mice of different ages and genders and its possible mechanism.Methods:80 clean grade healthy C57BL/6J mice were divided into two groups:the young group(6-8 weeks old)and the adult group(16-18 weeks old),40 mice of each age group,half male and half female,were raised in cages and fed adaptively for one week.Then the mice of each age group were randomly divided into the male normal salt group(containing 0.5%NaCl feed,NS),the male high salt group(containing 8%NaCl feed,HS)the female normal salt group,the female high salt group,10 mice in each group.The blood pressure of tail artery was measured once a week for 3 weeks.The 24-hour urine of each group of mice was collected in the metabolic cage;the serum creatinine,blood urea nitrogen,24-hour urine microalbumin(mALB),24-hour urine sodium and potassium content were measured in 3 weeks,and the 24-hour urine sodium/potassium ratio was calculated;the renal morphology and fibrosis were observed by HE,PAS and Masson staining.Detection of serum estrogen and renal angiotensin(1-7)in mice by ELISA.Col?,Col ?,Kim-1,?-SMA,vimentin,E-cadherin,ACE2,MasR,ACE,Ang ? and AT1R were detected by immunohistochemistry;Western blotting was used to detect Col ?,Col?,Kim-1,?-SMA,vimentin,E-cadherin,TGF-?1,p-smad3,ACE2,MasR,Ang ? and AT1R.Results:I.In C57BL/6J mice of the young group(6-8W):there was no significant difference in the tail artery systolic pressure between the groups in the third week(P>0.05).Compared with the same sex NS group,24-hour mALB,24-hour sodium,24-hour potassium and 24-hour sodium/potassium ratio in HS group were all increased(P<0.05).The glomerulosclerosis index,glomerular fibrosis index and renal interstitial fibrosis index of HS group were higher than those of NS group(P<0.05),while The glomerulosclerosis index,glomerular fibrosis index and renal interstitial fibrosis index of female mice in HS group were lower than those of male mice(P<0.05).The content of estrogen in serum of female rats was higher than that of male rats in the same group.Compared with the same sex NS group,the Ang(1-7)content of HS group decreased,while the expression of Col ?,Col ?,Kim-1,?-SMA,vimentin,TGF-?1,p-smad3,ACE,Ang ? and AT1R protein increased(P<0.05),The expression of E-cadherin,ACE2 and MasR protein decreased(P<0.05);compared with male HS group,the expression of Ang(1-7)increased(P<0.05),Col ?,Kim-1,ACE,Ang ? and AT1R protein decreased(P<0.05),and the expression of ACE2 and MasR protein increased(P<0.05).?.In C57BL/6J mice of the adult group(16-18w):at the third week of the experiment,the systolic blood pressure of the tail artery in male HS group was higher than that in male NS group(P<0.05).Compared with the same sex NS group,the blood urea nitrogen,24-hour mALB,24-hour sodium,24-hour potassium and 24-hour sodium/potassium in HS group were all increased(P<0.05).The glomerulosclerosis index,glomerular fibrosis index and renal interstitial fibrosis index of HS group were higher than those of the same sex NS group(P<0.05),The glomerulosclerosis index,glomerular fibrosis index and renal interstitial fibrosis index of female mice in HS group were lower than those of male HS mice(P<0.05).The content of estrogen in serum of female rats was higher than that of male rats in the same group.Compared with the same sex NS group,the Ang(1-7)content of HS group decreased,while the expression of Col ?,Col ?,Kim-1,?-SMA,vimentin,TGF-?1,p-smad3,ACE,Ang ? and AT1R protein increased(P<0.05),The expression of E-cadherin,ACE2 and MasR protein decreased(P<0.05);compared with the male HS group,the expression of Ang(1-7)increased(P<0.05),Col ?,Col ?,Kim-1,?-SMA,vimentin,TGF-?1 p-smad3,ACE,Ang ? and AT1R protein decreased(P<0.05),and the expression of ACE2 and MasR protein increased(P<0.05).Conclusion:I.Short term high salt diet can induce renal fibrosis in C57BL/6J mice through blood pressure dependent pathway or non blood pressure dependent pathway;?.tubuloepithelial mesenchymal transformation is involved in the pathological process of short-term high salt induced renal fibrosis in C57BL/6J mice;?.TGF-?1/Smads pathway and activation of local Renin-angiotension system are involved in the mechanism of short-term high salt induced renal fibrosis in C57BL/6J mice;?.Short term high salt induced renal fibrosis in mice is closely related to age and gender,The mechanism may be related to the activation of ACE2 ang(1-7)-MAS receptor axis and inhibition of ACE-Ang ?-ATiR classical axis in female rats.