Combination Benopril And Losartan Therapy Cyclosporine A Chronic Nephrotoxicity

[Background and Objective] Cyclosporine A (CsA),one of common immunosuppressive, is widely used in many diseases relative to immunity. But the incidence of CsA nephrotoxicity has increased in recent years. CsA chronic nephrotoxicity (CsA-CNT) is always the main cause of the ESRD of the CsA receiver , the 15% disease incidence, with the dangerous factors:higher dosage,male receiver,actue renal failure.The syndrom of CsA-CNT is, higher serum creatinine, systemic hypertension, proteinuria, with or without b100d uria . Morphological findings associated with CsA-CNT include focal interstitial fibrosis , tubular atrophy , obliterative vase -ulopathy and focal glomerulosclerosis. Dosage extenuation or withdraw is no available of CsA-CNT. Renin-angiotensin system (RAS) plays an important role in the mechnism of CsA-CNT. It is the most important step in the process that RAS activing , angiotensin II(AngII) up-regulating .So how to hinder RAS efficiently is the main way to prevent the fibrosis development of the renal failure. Angiotensin converting enzyme inhibitor(ACEI) can protect the renal function by inhibiting angiotensin converting enzyme (ACE). Angitensin receptor blocker (ARB) can impede the function of AngII in thelast step by the way of combinating with the angiotensin II type 1 receptor (ATI) receptors.It was reported that AngII has more ways being produced than ACEI can inhibited .ARB doesn' t inhibit Angll to combinate with AT2 receptor. ACEI and ARB can impede RAS by the different way . In theory, comb int ion ACEI and ARB can protect renal function more efficiently. It has become the hot spot in recent years. So it is reasonable for us to propose the following hypothesis: in the treatment of CsA-CNT .better effects may be made by combination benopril and losartan by the way of hindering RAS more efficiently, we establish a rat model of CsA-CNT to explore the hypothesis and the mechnism.[Methods] A rat model of CsA (15mg/(kg. d), i. s.) was established. Benopril , losartan or combination was gived to these rats in a dose of 10 mg/(kg. d). The tubular function and glomerular function and renal morphology were observed at the end of 2 weeks and 4 weeks after gavage of benopril, losartan and combination. Kidneys were harvested after 2 and 4 weeks .Angll was immunoradiometried by kit. MASSON staining was performed , as well as transforming growth factor-betal(TGF-B1), collegan III(ColIII) were immunostained by LSAB kit. [Results]1. 2 weeks after therapy,(1). The Ccr in each therapy group was significantly lower than control groups ( P<0.05 ) .But there were no significant difference between them. P>0. 05) .(2).The concentration of Angll in benopril group was lower than model group significantly (P<0. 05) . The concentration of Angll in losartan group was higher than other groups significantly (P0.05).(3). There were no significant ratio of fibrosis difference between them (P>0.O5) .(4). The ratio of TGF-B1 in each therapy group was significantly higher than control and lower than model group. The ratio of TGF- 3 1 in combination group was significantly lower than benopril and losartan groups (P<0.05) .(5). There were no significant ratio of Col III difference between them (P>0.O5).2. 4 weeks after therapy,(1). The Ccr in each therapy group was significantly lower than control groups (P<0.05) .But there were no significant difference between them(2).The concentration of Angll in benopril group was lower than model group significantly (P<0.05) . The concentration of Angll in losartan group was higher than other groups significantly (P<0.05) . But there were no significant difference between model group and combination (P>0.05) .(3). The ratio of fibrosis in each therapy group was significantly higher than control and lower than model group. The ratio of fibrosis in combination group was significantly lower than benopril and losartan groups(4). The ratio of TGF-B1 in each therapy group was significantl...