Protective Effects Of Clerodendranthus.S And Ursolic Acid In Mice Aristolochic Acid Nephropathy

Objective To investigate the renal pathological changes,and to observe the effectsthe cytokine Transforming growth factor-β1(TGF-β1), and Connective tissuegrowth factor(CTGF)expression by Ursolic acid intervertion on mice Aristolochicacid nephropathy models(AAN). The aim is to provide a new experimental basis forthe clinical treatment of AAN and seek new drugs for the treatment of AAN.Methods Fifty ICR male mice of23-25g, were randomly divided into normalcontrol group, model group, model+high doses Ursolic acid intervention group(200mg/kg), model+low dose Ursolic acid intervention group (100mg/kg)， CSextracts intervention group (10g/kg).The AAN model was established by igaristolochic acid-Ⅰ8mg/kg once. Intervention group received high dose Ursolicacid，low dose Ursolic acid and CS extract ig，respectively, normal control groupand model group with equal-volume normal saline once a day for4weeks，andmeasured body weight, qod. Urine collected24days after ig was used to detect Urineprotein. After4weeks，we collected blood sample from the infraorbital vessels tomeasured SCr，BUN，and kidneys were collected with HE staining and evaluate therenal pathological changes and microstructure observation computer image analysiswas carried out to evaluate immunohistochemical expression of TGF-β1、CTGF inthe kidney.Results1.Body weight and condition in mice: Normal control group body weightincreases; the model group were apathetic and thin body，and even death. Thereduction of body weight in drug intervention group mice is less.2.content of Urinary protein：Compared with the normal control group,contents of urine protein of model group were increased (P <0.05).compared withmodel group, the high dose Ursolic acid group were significant reduced (P<0.05).3. SCr measure：Model group, compared with the normal control group, Cr in serum of model group were increased (P<0.05), compared with model group, the highdose, low dose ursolic acid group and CS extracts were significant reduced(P<0.05).BUN measure: compared with model group, the high dose ursolic acidgroup also reduced (P<0.05).4. HE staining: Renal tissues were not significant changes in normal control groupmice. The renal tubulointerstitial lesions of model group mice were obvious, withinfiltrating of inflammatory cells in tissues, swelling of tubular epithelial cells, tubulardilation atrophy obviously the tubulointerstitial lesions developed the fibrosis, Part ofthe tubular lumen tube appears. High dose Ursolic acid group and CS extractsintervention group the tubulointerstitial lesions were relatively relieved.5. The semi-quantitative analysis of immunohistochemical staining:①Comparedwith normal control group, the expression of TGF-β1and CTGF in thetubulointerstium were all significant increased in model group (P<0.05).②Comparedwith model group, The expression of TGF-β1and CTGF in high dose Ursolic acidgroup and CS extracts intervention group were significant reduced (P <0.05).③Compared with model group，the expression of TGF-β1and CTGF in CS extractsgroup also showed significant reduced(P<0.05).Conclusion①Aristolochic acid-Ⅰ can stimulate TGF-β1and CTGFexpression increased in mice renal tubules，and make the model group and the drugintervention group had renal interstitial fibrosis；②In renal injury process of AANmodels, TGF-β1and CTGF expression were decreased by Ursolic acid and CSextracts group intervention，Between Ursolic acid and CS extracts group nosignificant difference in the inhibition of renal tubular intertitial fibrosis.