The Effects Of Bone Marrow Mesenchymal Stem Cells On Folic Acid Induced Acute Kidney Injury In Immature Mice

Objective:Acute kidney injury?AKI?is a worldwide spread kidney disease,presenting sudden loss of renal function with high mortality.With unhealthy living habits,environmental pollution and drug abuse,More and more kidney injury occurs year by year,especially in infants and young children,in which the incidence of AKI increasing,but the molecular mechanism remains unknown.In this study,we want to know whether the renal impairment is associated with age and underlying mechanism.At present,there is rare better treatment of AKI especially in infants and young children clinically.Stem cell therapy is the hotspot in the treatment of acute kidney injury.Therefore,We explored the effects of mouse bone marrow mesenchymal stem cells?MSCs?on the immature mice with FA-induced AKI mice and further discover new factors.All these will aid us to understand the new pathogenesis of AKI in infants and simultaneously uncover new molecular mechanisms for MSCs to treat AKI.Methods:Part 1:FA-induced AKI mouse model was established to compare AKI between 4 weeks old young mice and 8 weeks old mice.At 1^st And 2^ndday,the kidney damage of FA-AKI mice were evaluated by detecting renal injury index?plasma Cr and BUN levels,kidney/body weight ratio,renal tubular lesionson HE staining?and further explore the mechanisms:inflammatory factors?IL17?;renal vascular endothelial growth factor?Ang-1,Ang-2?,renal tubular protective factor?SIRT1?and renal tubular epithelial cell autophagic factor?Beclin1,LC3?.Part 2:On the basis of the first part,the therapeutic effect of MSCs on 4 weeks old FA-AKI immature mices was studied.After injection of MSC,the therapeutic effect was observed by detecting the renal injury index?plasma Cr and BUN level,kidney/body weight ratio,HE staining to observe renal tubular lesions?.And the related molecular mechanism was researched:inflammatory factor?IL17?,renal vascular growth factor?Ang-1,Ang-2?,renal tubular protective factor?SIRT1?,autophagic factor of renal tubular epithelial cells?LC3,Beclin1?.Results:Part 1:After FA induced AKI,compared with 8 weeks of mice,BUN and Cr levels are higher in 4 weeks old mice,as well as Kidney/body weight ratio;the relative area of renal tubular vacuoles increased,the level of IL17 increased.But the level of LC3and Beclin1 in 4 weeks old mice were significantly lower than 8 weeks mice,and the expression level of Ang-1 was significantly lower than that of 8 weeks mice.Ang-2 level was higher than that of 8 Weeks mice,also SIRT1 was significantly less than 8 weeks in mice.Results:Part 2:One or two days after MSCs treatment,compared with the control group,the levels of BUN and Cr in the treatment group were lower,the ratio of renal and body weight,the relative area of renal tubular vacuoles and the level of inflammatory factor IL17 decreased.Histochemical results showed that the autophagy factor LC3,the expression level of Ang-1 was significantly higher than that of the control group,but the level of Ang-2 was significantly lower.Importantly,compared with the control group,the renal protective factor SIRT1 was significantly higher.Conclusion:1.The degree of acute renal injury induced by FA is related to age:the youngermice,more the kidney injury was presented.This may be associated with renal vascular growth factor Ang-1/Ang-2 imbalance,inflammatory factor IL17 increased,autophagic factor LC3,Beclin-1 and renal tubular protective factor SIRT1 decreased,which will explain newly why younger child was predisposed to suffer AKI.2.MSCs ameliorated folic acid induced AKI through the vascular protection,inhibition of inflammation and increasing autophagy and SIRT1 level.These results will bring new theoretical basis for applying MSCs in clinical AKI.