Impact of Lotensin and Salviae on the Changes of TGF-Beta1 and Its Receptors in a Rat Model of Chronic Cyclosporine-Induced Nephropathy

ObjectivesTransforming growth factor-beta1 (TGF-β1) and its receptors, type 1 (TR-1) and type 2 (TR-2) play important roles in chronic cyclosporine (CsA)-induced nephropathy. Lotensin is known as an angiotensin-converting enzyme inhibitor and may reduce chronic CsA-induced nephropathy. Recently it is reported that Salviae (a Chinese medicine), which can improve microcirculation and decrease the expression of TGF-β1 has the same effect as that of lotensin. Therefore, in this study we assessed the effects of Lotensin or Salviae on the chronic CsA-induced upregulation of TGF-β1, TR-1, and TR-2 in a rat model.Materials and methodsSodium-depleted rats were administered CsA by gastric gavage and a new rat model of chronic CsA-induced nephropathy was established. Rats with chronic CsA-induced nephropathy were treated by lotensin or Salviae. The proteins of TGF-β1, TR-1, and TR-2, and the mRNA of TR-1 and TR-2 in the kidneys of CsA-treated rats, were measured by immunohistochemistry (IHC) and in situ hybridization (ISH). The results were investigated semiquantitatively by image analysis.ResultsLotensin or Salviae individually attenuated CsA-induced nephropathy in the rat models, and downregulated the protein expressions of TGF-β1, TR-1, and TR-2, and the mRNA transcripts of TR-1 and TR-2 in the rat model.ConclusionOur studies show that treatment with lotensin or Salviae is useful in preventing chronic CsA-induced nephropothy.