Impact of Lotensin and Salviae on the changes of TGF-beta1 and its receptors in a rat model of chronic cyclosporine-induced nephropathy.
OBJECTIVE
Transforming growth factor-beta(1) (TGF-beta(1)) 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-beta(1) 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-beta(1), TR-1, and TR-2 in a rat model.


METHODS
Sodium-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-beta(1), 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.


RESULTS
Lotensin or Salviae individually attenuated CsA-induced nephropathy in the rat models, and downregulated the protein expressions of TGF-beta(1), TR-1, and TR-2, and the mRNA transcripts of TR-1 and TR-2 in the rat model.


CONCLUSIONS
Our studies show that treatment with lotensin or Salviae is useful in preventing chronic CsA-induced nephropothy.
Peng
B
B
Department of General Surgery, West China Hospital, West China Medical School, Sichuan University, Guoxuexiang 37, Chengdu 610041, P.R. China. Pengbing84@hotmail.com
Li
M
M
Niu
T
T
He
S
S
D030201:Activin Receptors, Type I / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D016572:Cyclosporine / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D023421:Models, Animal; D017346:Protein Serine-Threonine Kinases; D051381:Rats; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D027544:Salvia; D014020:Tissue Extracts / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D018125:Receptors, Transforming Growth Factor beta; D014020:Tissue Extracts; D016212:Transforming Growth Factor beta; D016572:Cyclosporine; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625843:Tgfbr1 protein, rat; C044946:benazepril