【摘 要】
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Aim Thromboxane A2 (TXA2) is assumed to contribute to the process of renal dysfunction.The present study was designed to investigate whether terutroban, a specific antagonist of thromboxane/prostaglan
【机 构】
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Department of Urology,Zhongshan Hospital,Fudan University,Shanghai 200032,China
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Aim Thromboxane A2 (TXA2) is assumed to contribute to the process of renal dysfunction.The present study was designed to investigate whether terutroban, a specific antagonist of thromboxane/prostaglandin?(TP) receptor, protects against renal damage in 5/6 nephrectomy.Methods C57/BL6 mice were randomly grouped into shamoperated (2K), 5/6 nephroectomy groups (5/6Koff) and 5/6 nephroectomy treated with terutroban (10 mg · kg1 · d1) groups (Terutroban).Renal artery and kidney were collected for vascular function study, Western blot, immunohistochemistry (IHC) assay and enzymelinked immunosorbent assay (ELISA), respectively.Results Four weeks after the surgery, arterial blood pressure was comparable among the three groups.However mice in terutroban group had higher levels of serum creatinine and lower survival.Compared with 2K groups, 5/6Koff mice had significantly higher levels of renal blood flow as well as a blunted relaxation to acetylcholine.Production of prostacyclin (PGI2) and thromboxane B2 (TXB2), but no prostaglandin E2 (PGE2), were significantly increased in the renal artery of 5/6Koff group.Terutroban restored the renal blood flow, but not the acetylcholineinduced relaxation in the renal artery.It is probably due to the blockade effect of terutroban on the smooth muscle since terutroban treatment significantly reduced U46619induced vasconstriction in renal arteries.Interestingly, terutroban increased the production of TXB2, but not PGI2 or PGE2, in the renal artery.This probably is a compensatory effect on prostaglandins production.In kidney cortex, 5/6Koff group had significantly lower levels of PGE2 and TXB2 when compared with 2 K group.Terutroban markedly increased all three prostaglandins levels.Conclusion Terutroban restores renal artery function, but not renal function in mouse with 5/6 nephrectomy.It suggests that kidney has more complicated regulations than renal artery.High levels of prostanoids in kidneys may contribute to renal damage in terutroban group.Further experiments will focus on examining the underlying mechanisms.
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