Preliminary Study Of Immune Pathological Mechanism Underlying A Mouse Model Of Aristolochic Acid Nephropathy

Objective To investigate the changes of lymphocyte subsets in the mouse blood and spleen underlying aristolochic acid nephropathy(AAN),observe the pathological changes in the kidney and discover immune pathological mechanism underlying a mouse model of AAN,which provides a new therapeutic way for the treatment of immune intervention of AAN.Methods AAN mouse model was made with AAâ… and samples of blood,spleen and kidney were collected for detecting renal function,lymphocyte subsets,histologic changes.Results Renal function showed the levels of BUN,creatinine,uric acid increased significantly after the 3,10 days of intraperitoneal injection of aristolochic acidâ… (AAâ… ), and gradually declined after the 21 days, increased again after the 35 days.FCM showed CD3+,CD4+,CD8+,4-1BB+lymphocytes subsets in the mouse blood and spleen were significantly higher than that in the control group after the 3,10 days of intraperitoneal injection of AAâ… ,and gradually decreased after the 10,21 days,rised again after 35 days, which corresponded well to the changes of renal function.Histologic changes showed there were swelling,degeneration,necrosis in the tubular epithelial cells and no significant changes in the renal interstitial area at the early stage.At the later stage shrink,collapse of the tubular epithelial cells and renal tubule interstitial fibrosis were found.A large number of lymphocytes infiltrated around renal interstitial and vascular.Immunohistochemistry showed that there were infiltration of CD3+T lymphocyte in the tubule interstitial area and the over expression of CD40 in the tubule cells.Conclusion 1.We built a mouse model of aristolochic acid nephropathy with large doses of AAâ… ,which presented acute kidney injury at the early stage and entered the chronic tubule interstitial fibrosis at the later stage. 2.There were immune dysfunction in AAN,which showed CD3+,CD4+,CD8+,4-1BB+ unbalance and the infiltration of CD3+ in the tubule interstitial area and the over expression of CD40 in the tubule cells.3.Up-regulation of 4-1BB in single nucleus cells of the blood and spleen and the over expression CD40 in the tubule interstitial cell might provide specific target molecules for the treatment of immune intervention of AAN.