Objective To investigate the preventive effects of Ginkgo biloba extract (Egb) on cyclosporine A (CsA) -induced cell apoptosis and expression of p27 in renal tissues 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. CsA or vehicle was subcutaneously injected once a day, and Egb was administrated orally. After 4 weeks the animals were sacrificed. The weights of the animals were measured; 24 h-urine samples were collected to measure the content of urinary protein; the blood samples were collected for SCr, BUN measurement. The kidney tissues were sectioned for histological analysis; cell apoptosis in renal tissues were examined using the terminal deoxynucleotidyl transferase(TdT)-mediated dUTP in situ nick and labeling (TUNEL) method and p27 expression was detected by immunohistochemistry. Results Compared with the control group, the urinary volume, 24 h urinary protein in CsA group were increased and presented renal tubulointerstitial fibrosis; the numbers of apoptotic cells and p27 positive cells were also significantly increased. Treatment with Egb significantly decreased 24h urinary protein, renal tubulointerstitial fibrosis injury; the numbers of apoptotic cells and p27 positive cells were also lower in two Egb treatment groups (P < 0. 05). Conclusion Egb can effectively attenuate renal tubular degenerative necrosis, renal interstitial fibrosis, subsequently decrease the CsA-induced nephrotoxicity.%目的 观察银杏叶提取物(EGb)对环孢素A(CsA)所致肾组织细胞凋亡及p27表达的影响,探讨CsA的肾保护作用机制.方法 雄性Wistar大鼠随机分为对照组、小剂量CsA组每日(皮下注射CsA,25 mg/kg)、大剂量CsA组(皮下注射CsA,50 mg/kg)、小剂量CsA+ EGb治疗组(皮下注射CsA,25 mg/kg,Egb,300 mg/kg灌胃)、大剂量CsA+ EGb治疗组(皮下注射CsA,50 mg/kg,Egb,300 mg/kg灌胃),给药4周后测定各组大鼠体质量、尿量、24h尿蛋白、肾功能.并行肾脏病理检查,免疫组化检测肾脏p27表达水平及肾组织细胞凋亡情况.结果 与对照组相比,所有CsA模型组及EGb治疗组尿量、尿蛋白均增加；肾间质纤维化评分增加,且大剂量组较小剂量组更为严重；免疫组化结果显示细胞凋亡数及p27阳性细胞数明显增加,且大剂量组较小剂量组升高更为显著；EGb治疗组尿蛋白减少、肾间质纤维化评分下降、细胞凋亡、p27阳性细胞数明显减少.结论 CsA使肾小管上皮发生细胞周期阻滞,诱发以肾小管间质细胞为主的肾细胞凋亡可能是CsA慢性肾毒性发病机制之一.EGb可减少细胞凋亡,减轻CsA导致的肾小管变性坏死、肾间质纤维化,发挥肾保护作用.
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