目的观察血管紧张素转换酶2(ACE2)在腺嘌呤致肾间质纤维化大鼠肾脏组织中的表达水平及银杏叶提取物(EGb761)对其表达水平的影响。方法 24只腺嘌呤致肾间质纤维化模型大鼠,随机分成模型对照组、EGb761组和氯沙坦治疗组。EGb761治疗组大鼠予银杏叶提取物片[100 mg/(kg.d)]混悬液灌胃;氯沙坦治疗组大鼠予氯沙坦[10 mg/(kg.d)]混悬液灌胃;模型组予等量蒸溜水灌胃;另设正常对照组,8只予等量蒸溜水灌胃,治疗周期为30 d。在实验结束时,留取血、尿、肾组织标本,进行血清肌酐(Scr)、尿素氮(BUN)、24 h尿蛋白量(24 h MTP)等检测,及肾组织病理形态学观察。采用免疫组化和定量荧光定量PCR(Real Time PCR)测定肾组织ACE2蛋白及mRNA表达水平。结果 EGB761组和氯沙坦组大鼠血清肌酐(Scr)、尿素氮(BUN)24 h尿蛋白定量明显下降,与模型组比较具有显著统计学差异(P〈0.01)。免疫组化和RealTime PCR结果显示,模型组ACE2蛋白及mRNA表达水平较正常组显著减少(P〈0.01),银杏叶提取片、氯沙坦均可增加ACE2蛋白及mRNA的表达水平,与模型组比较具有显著统计学差异(P〈0.01)。结论银杏叶提取物片能降低肾间质纤维化大鼠的血清肌酐、尿素氮,减少24 h MTP,具有肾功能保护作用,其机制可能与上调ACE2蛋白和mRNA表达水平而发挥抗肾间质纤维化的作用相关。
AIM To observe angiotensin-converting enzyme 2(ACE2) level in rats with renal interstitial fibrosis induced by adenine,and effects of extract Ginkgo biloba 761(EGb761) on ACE2 expression level.METHODS Twenty-four rats with renal fibrosis were randomly divided into EGb761 group,losartan group and control group(eight rats each group),eighteen rats as normal group.EGb761 group received EGb761 suspension 100 mg/(kg·d),losartan group received losartan suspension 10 mg/(kg·d),and the normal group and control group received the distilled water by gavage.The rats were sacrificed after 30 days’ medication,blood,urine and kidneys samples were collected for kidney function,albuminuria and pathomorphology analysis.Immunohistochemistry and Real Time PCR were used to detect the amount of ACE2 protein and mRNA expression.RESULTS Serum creatinine(Scr),blood urea nitrogen(BUN),24-hour urine protein(24hMTP) in the control group were significantly higher than that in the normal group(P〈0.01).Compared with the control group,Scr,24hBUN and MTP of EGb761 and losartan group decreased significantly(P〈0.01).Immunohistochemistry and Real Time PCR results showed that renal tissue ACE2 protein of the control group decreased as compared with normal group;while renal tissue ACE2 protein in EGb761 and losartan group was significantly increased compared with control group(P〈0.01).CONCLUSION EGb761 could lower the serum urea nitrogen and creatinine,and 24 h urinary protein,and increase ACE2 protein and mRNA expression in rat with renal interstitial fibrosis induced by adenine.