摘要
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、24 h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。
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（25mg/kg） group,CsA（50mg/kg） group,CsA（25mg/kg） ＋ EGb（300mg/kg） group and CsA（50mg/kg） ＋ EGb（300mg/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,24h 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（P0.05）.Conclusion EGb can effectively attenuate renal tubular degenerative necrosis,renal interstitial fibrosis,subsequently decrease the CsA-induced nephrotoxicity.
出处
《同济大学学报（医学版）》
CAS
2012年第6期52-57,共6页
Journal of Tongji University(Medical Science)
