Cyclosporin A Tripterygium Monomer T <sub> 4 </ Sub> On The The Human Mesangial Cell Proliferation And Secretory Function

Cyclosporine A has been used in the treatment of idiopathic nephritic syndrome with a great success. The nephrotoxicity limits its wider use in human diseases The mechanisms of CsA-induced nephrotoxicity remains unclear.It has been reported that decreased production of PGE₂,PGI₂, NO and increasd synthesis of collagen by renal cells in culture may involved in the pathogenesis of the nephrotoxicity.Both the immunosuppression and side effcts of CsA is dose dependent and it is speculated that a lower dose of CsA combined with other immune inhibitors might keep a greater degree of immunosuppression but with less nephrotoxicity.Tripcholork'de (T₄), an active abstract from a Chinese herbal medicine Tripterygium wilfordii Hook-F (TW),has stronge anti-inflammatory and immunosupressive activities.In this study, human mesangial cells were cultured with CsA and/or T₄ at different concentrations. HMC proliferation, IL-6 , collagen,TGF β mRNA expression and protein production were mesured and the mechanisms of actions of CsA and T₄ were elucidated further. On the basis of comparison between the actions of a lower dose of CsA combined with T₄ and a large dose of CsA, the speculation was evaluated that a lower dose of CsA combined with T4 could reach a greater degree of immunosuppression but with less nephrotoxicity.1 .The effects of CsA combined with T₄ on cultured HMCs proliferation.HMC were cultured in the media containing different concentrations of CsA , T₄ or both for a total 72 hours and [³H]-TdR incorporations in the last 24 hours were mesured . Both CsA and T₄ inhibited HMC proliferation in a dose dependent manner. Combination of the two drugs produced an additional suppression. [³H]-TdR incorporations was lower in group treated with CsA , 0.1μg/ml with T₄, 0.625 ng/ml than that with CsA, 1.0 μg/ml . p < 0.05. The effects of CsA and T₄ was almost completly...