Takada S, Takahara S, Nishimura K, Ichimaru N, Hongsi J, Kokado Y, Kitamura M, Matsumiya K, Matsumoto K, Nakamura T, Okuyama A
Department of Urology, Osaka University Medical School, Suita, Japan.
Transpl Int. 1999;12(1):27-32. doi: 10.1007/s001470050181.
Renal toxicity is a serious side effect of therapy with tacrolimus (FK506), an immunosuppressive agent administered to renal transplant recipients. We investigated the effect of hepatocyte growth factor (HGF) on tacrolimus-induced nephrotoxicity in spontaneously hypertensive rats (SHR). After a right nephrectomy, rats received a continuous perfusion of either HGF in a dose of 5 microg/kg daily (tacrolimus + HGF group) or normal saline (tacrolimus group) into the left renal artery at a rate of 1 microl/h for 7 days after surgery. Tacrolimus was injected intramuscularly in a dose of 4 mg/kg daily for 10 days after surgery. HGF significantly inhibited the tacrolimus-induced increase in the serum creatinine (SCr) level (P < 0.05). HGF also prevented the tacrolimus-induced loss in body weight. The bromodeoxyuridine (BrdU) index was significantly higher in kidney specimens from the tacrolimus + HGF group. These findings suggest that HGF induces the regeneration of renal tubular cells and suppresses tacrolimus-induced renal toxicity in SHR.
肾毒性是给予肾移植受者的免疫抑制剂他克莫司（FK506）治疗的严重副作用。我们研究了肝细胞生长因子（HGF）对自发性高血压大鼠（SHR）中他克莫司诱导的肾毒性的影响。右肾切除术后，大鼠在术后7天以1微升/小时的速率向左肾动脉连续灌注每日剂量为5微克/千克的HGF（他克莫司+HGF组）或生理盐水（他克莫司组）。术后10天，每天肌肉注射剂量为4毫克/千克的他克莫司。HGF显著抑制了他克莫司诱导的血清肌酐（SCr）水平升高（P<0.05）。HGF还防止了他克莫司诱导的体重减轻。他克莫司+HGF组肾标本中的溴脱氧尿苷（BrdU）指数显著更高。这些发现表明，HGF可诱导肾小管细胞再生，并抑制SHR中他克莫司诱导的肾毒性。
