Effects Of Akkermansia Muciniphila On Renal Function In Rats With Chronic Kidney Disease And Its Mechanism

Objective:To study the improvement effect of Akkermansia muciniphia(A.muciniphila)on renal function and renal pathology in rats with chronic kidney disease(CKD),and to determine the effect of A.muciniphila on inflammatory factors in the kidney tissue of rats with chronic kidney disease.To explore the effect of A.muciniphila on the improvement of renal function in rats with chronic kidney disease and its possible immune regulation mechanism.Thus providing a new direction for the treatment of CKD.Methods:A.muciniphila strains was cultured and CKD rat model was established.33 male SD male rats were randomly divided into four groups and gavaged respectively with0.9%Na Cl(control group,n=7),adenine(model group,n=7),adenine and A.muciniphila simultaneously(prevention group,n=10)or adenine fallowed by A.muciniphila(treatment group,n=9).the blood urea nitrogen(BUN)and serum creatinine(Scr)values of each group were measured by automatic biochemical analyzer,and the renal function was evaluated;the changes of tubular basement membrane thickness and the renal interstitial fibrosis were observed using Glycogen(PAS)staining and Masson’s trichrome staining(MTS);The expression of anti-inflammatory factor IL-10 and pro-inflammatory factor IL-1β,TNF-α in kidney tissue were determined with immunohistochemistry and western blotting;statistical analysis was performedResults:A CKD animal model was successfully established.Compared with the control group rats,the BUN and Scr values of rats in the CKD model group were significantly increased(F=86.2710,F=80.2800,all P<0.01).After A.muciniphila intervention,compared with the CKD model group rats,the prevention group and treatment group the BUN and Scr values of rats in the group were significantly decreased(F=86.2710,F=80.2800,all P<0.01).Compared with the control group rats,rats in the CKD model group had obvious renal pathological tissue damage:the tubular basement membrane was significantly thickened,and the renal interstitium was significantly fibrotic(F=15.9040,F=6.5330,all P<0.05).After A.muciniphila intervention,compared with the CKD model group rats,the renal pathological tissue of rats in the prevention group and the treatment group was significantly improved:the tubular basement membrane thickened and the renal interstitial fibrosis was significantly alleviated,among which the prevention group was more pronounced(F=15.9040,F=6.5330,all P<0.05).Compared with the control group rats,the expression of anti-inflammatory factor IL-10 in kidney tissue of rats in CKD model group was significantly decreased,and the expression of pro-inflammatory factor IL-1β and TNF-α was significantly increased(F=14.8060,F=5.6350,F=5.7420,all P<0.05).After the intervention of A.muciniphila,compared with the CKD model group rats,the expression of anti-inflammatory factor IL-10 in the kidney tissue of rats in the prevention and treatment groups was significantly increased,and that of the pro-inflammatory factor IL-1β and TNF-α was significantly decreased(F=14.8060,F=5.6350,F=5.7420,all P<0.05).Conclusion:A.muciniphila may improve renal function in rats with chronic kidney disease by inhibiting chronic systemic microinflammation.