Expression And Significance Of ACE2-Ang(1-7)-Mas Axis In Tubulointerstitial Fibrosis Induced By Cyclosporine

Objective: To investigate the expression of ACE2-Ang (1-7)-Mas axis, and assess theeffects of Ang (1-7) on tubulointerstitial fibrosis in chronic tubule interstitial fibrosisinduced by cyclosporine A(CsA).Methods: Sprague-Dawley rats which feed with low-salt diet were randomly divided intothe following groups: model group (cyclosporine+olive oil), treatment group(cyclosporine+olive oil+Ang (1-7)) and control group. Chronic cyclosporinenephropathy rat model was established with cyclosporine25mg/kg/day gavage, andtreated with controlled release of Ang (1-7) at a dose of576ug/kg/day from mini-osmoticpump. The model group rats were sacrificed at5days,10days,15days and28days,while the treatment group rats were killed at28days. The general status, renal function,and histopathological changes of renal tissue were observed. The level of serum Ang (1-7)and Ang II level were detected by ELISA methods. The expressional levels of ACE2,Mas, TGFβ and FSP1in rat renal tissue were detected by immunohistochemistry, ACE2,TGFβ mRNA were observed by Real Time-PCR method.Results: The body weight of rats in model group decreased gradually with the extensionof CsA administrate time, and was lower than that in the treatment group at28days（P＜0.05）. The level of serum creatinine(Scr) and urea in the model group was progressivelyincreased, and Scr level was higher than that in the treatment group at28days（P＜0.05）. The renal tubular injury, inflammatory cells infiltration and interstitial fibrosis inmodel group were gradually aggravated by histologic examination, while these changeswere alleviated in the treatment group. The levels of serum Ang (1-7), and Ang II in themodel group were increased with different degrees. Compared with model group at28days, Ang (1-7) level in the treatment group was significantly increased (P<0.01), whiledecreased AngII level was no statistical significance. The immunostaining score of ACE2,Mas, TGF-β, and FSP1of renal tissue in the model and treatment groups were increased, but TGF-β and FSP1levels in the treatment group were significantly reduced ascompared with in the model group (P <0.05). The expressional levels of ACE2andTGF-β mRNA in the model group were upregulated with the peak levels at15and28days, respectively. No significant difference of ACE2mRNA level was found among thetreatment, model, and control three groups at28days.The TGF-β mRNA expressionallevel in the treatment group was significantly lower than that in the model group at28days (P<0.05).Conclusion: ACE2-Ang (1-7)-Mas axis is involved in process of renal interstitial fibrosisinduced by CsA, this effect may be associated with changes of Ang (1-7)/AngII ratio inthe latter part of the experiment. Exogenous Ang (1-7) can alleviate renal interstitialfibrosis induced by CsA.