ABSTRACT
Objective To compare the expression of renal transforming growth factor-?_1(TGF-?_1),its receptors type Ⅰ and Ⅱ(T?RⅠ and T?R Ⅱ) in two rat models of chronic nephropathy induced by CsA and FK506 respectively.Methods Rat models of chronic CsA-/FK506-induced nephropathy were established by administering sandimun Neoral and Prograf separately.Then their kidneys were dissected and the protein expression of TGF-?_1,T?RⅠand T?RⅡ,the mRNA levels of T?RⅠ and T?RⅡ was detected by using immunohistochemistry(IHC) and in situ hybridization(ISH) respectively.Results The IHC revealed that the integrated optical densities(IODs) of renal TGF-?_1,T?RⅠ and T?RⅡ were(605.24)?(140.24),(876.28)?(208.73) and(981.59)?(258.65) respectively in CsA-treated rats,(488.37)?(101.76),(586.63)?(131.21) and(543.34)?(105.26) respectively in FK506-treated ones.The ISH indicated that the IODs of renal T?RⅠ and T?RⅡ mRNA were(905.08)?(158.75) and(1090.92)?(242.73) respectively in CsA-treated rats,(661.37)?(205.65) and(716.27)?(195.55) respectively in FK506-treated ones.The difference of the above-mentioned five factors between the two groups was significant(P
ABSTRACT
Objective To explore the mechanisms of cyclosporin induced chronic nephrotoxicity. Methods Radioimmunoassay was used to study the changes of plasma renin activity (PRA), plasma angiotensin Ⅱ (AngⅡ), and Aldosterone after rats were given low salt diet and 30 mg?kg -1 ?d -1 of CsA for 28 days. The protective effects of Radix Salviae Miltiorrhizae or benazepril on these changes were also studied. Results In CsA treated rats, PRA and AngⅡlevels were significantly elevated as compared with control groups. The elevation was not influenced by injection of Radix Salviae Miltiorrhizae, but could be blocked markedly by benazepril. There was significant difference in Aldosterone levels among the groups except benazepril treated group showing a decreased Aldosterone level.Conclusion Chronic cyclosporone nephropathy may be related to activation of renin angiotensin system, especially to the elevation of AngⅡlevels. The different effects of Radix Salviae Miltiorrhizae or benazepril on RAS suggest the different preventive mechanisms of the two drugs to chronic cyclosporine nephropathy. The plasma Aldosterone levels were not elevated in CsA treated rats, suggesting that CsA may induce relative adrenal resistance to AngⅡ.