银杏叶提取物对环孢素A慢性肾毒性的拮抗作用

Ginkgo biloba extract relieves cyclosporine A-induced chronic nephrotoxicity

目的探讨银杏叶提取物(EGb)对环孢素A(CsA)所致慢性肾毒性的拮抗作用及其机制。方法将无特定病原体动物(SPF级)的雄性大鼠随机分为对照组、小剂量CsA组(皮下注射CsA25 mg.kg-1.d-1)、大剂量CsA组(皮下注射CsA50 mg.kg-1.d-1)、小剂量CsA+EGb治疗组(皮下注射CsA25 mg.kg-1.d-1,EGb 300 mg.kg-1.d-1灌胃)、大剂量CsA+EGb治疗组(皮下注射CsA50 mg.kg-1.d-1,EGb 300 mg.kg-1.d-1灌胃),给药4周后测定各组大鼠的体重、尿量、24 h尿蛋白定量、肾功能,并行肾脏病理检查,肾组织匀浆测定丙二醛(MDA)、总抗氧化能力(T-AOC)、过氧化氢酶(CAT)、还原型谷胱甘肽(GSH)。结果4个实验组的尿量、24 h尿蛋白定量、肾间质纤维化评分、MDA水平均显著高于对照组(P值均<0.05),内生肌酐清除率(Ccr)、T-AOC、CAT和GSH水平均显著低于对照组(P值均<0.05)。与小剂量CsA组相比,大剂量CsA组的MDA水平显著增高(P<0.05),T-AOC水平显著降低(P<0.05)。与大剂量CsA组相比,大剂量GsA+EGb治疗组的24 h尿蛋白定量、肾间质纤维化评分、MDA水平显著降低(P值均<0.05),Ccr、T-AOC、CAT和GSH水平显著升高(P值均<0.05)。与小剂量CsA组相比,小剂量GsA+EGb治疗组的24 h尿蛋白定量、肾间质纤维化评分显著降低(P值均<0.05),Ccr、T-AOC、CAT和GSH水平显著升高(P值均<0.05)。结论氧化应激是导致CsA肾毒性的主要原因之一,EGb能拮抗氧化应激反应,从而降低CsA肾毒性。

Objective To investigate the protective effects of Ginkgo biloba extract （EGb） on cyclosporine A （CsA）-induced chronic nephrotoxicity and the related mechanism. Methods Male Wistar rats （SPF） were randomly divided into 5 groups= control group, CsA （25 mg/kg） group, CsA （50 mg/kg） group, CsA （25 mg/kg） ＋ EGb （300 mg/kg） group and CsA （50 mg/kg） ＋ EGb （300 mg/kg） group. The rats were subcutaneously injected with CsA or vehicle every day, and were treated with EGb by oral administration. After four weeks, twenty-four hour urines were collected to measure the content of urinary protein and the weights of the animal were measured. Blood samples were collected to measure serum creatinine （SCr） and blood urea nitrogen （BUN）. Kidneys were removed rapidly for biochemical analysis of malonylaldehyde （MDA）, total anti-oxidation capacity（T-AOC） ,catalase （CAT） and glutathione （GSH）. The rest kidney tissues were sectioned for histological analysis. Results Compared with the control group, the urinary volume, 24 h urinary protein, renal tubulointerstitial fibrosis injuries and concentration of MDA were significantly higher in the other 4 groups （ P〈 0.05）; the creatinine clearance rate （Ccr）, T-AOC, GSH and CAT activities were significantly lower in the other 4 groups （P〈0.05）. The concentration of MDA was significantly higher in CsA （50 mg/kg） group than in CsA （25 mg/kg） group, and the T-AOC activities were significantly decreased （P〈 0.05）. Treatment with EGb significantly decreased 24h urinary protein, renal tubulointerstitial fibrosis injuries and concentration of MDA in two CsA model groups （P〈0.05）. Ccr, T-AOC, GSH and CAT activities were significantly increased in two EGb treatment groups （P〈0.05）. Conclusion Oxidative stress is one of the major reasons for CsA-induced nephrotoxicity; EGb can effectively inhibit the oxidative tress, subsequently decrease the CsA-induced nephrotoxicity. （Shanghai Med J, 2009, 32= 226-229）