FK506肾毒性的机理探讨及其防治研究

Nephrotoxicity of FK506 and its prevention

为研究ＦＫ５０６的肾毒性机理及防治，大鼠皮肤移植模型分组口服ＦＫ５０６、ＣｓＡ及钙离子拮抗剂异搏定。结果：组织形态学提示ＦＫ５０６与ＣｓＡ一样可引起肾小球系膜细胞增生，肾小管上皮细胞浊肿样变，同时使ＢＵＮ和ＳＣｒ增高，肾组织匀浆Ｐ４５０含量增加，表明其与ＣｓＡ一样损害肾功能。另外ＦＫ５０６使肾组织匀浆中内皮素（ＥＴ）、血栓素Ｂ_２（ＴＸＢ_２）和ＡⅠ、ＡⅡ增高，而ＰＧＩ_２下降，提示上述血管活性物质与肾毒性有关。应用异搏定（１０ｍｇ·ｋｇ_（－１）·ｄ_（－１））后，血ＢＵＮ、ＳＣｒ，及肾匀浆Ｐ４５０含量下降，同时肾小球系膜增生减轻，肾小管上皮细胞浊肿消失，提示异搏定对ＦＫ５０６的肾毒性有防治作用。

The nephrotoxicity of FK506 and CsA was studied in experimental animals with homologous skin graft.The histopathological changes were similar in both groups,These were glomerular mensangium hyper plasia and cloudy swelling of the renal tubule cells.Furthermore,there was a rise of serum BUN and SC,a rise of P450 in the renal tissue,an elevation of ET,TXB_2,AⅠand AⅡ and a decrease of PGI_2 in the renal tissue.All the above findings correlated with nephrotoxicity.Verapamil in a dose of 10mg·kg￣(-1)·d￣(-1) could decrease the serum level of BUN and SCr and abolish the cloudy swelling of renal tubules and therfore would able to prevent and treat the nephrotoxicity.