作　　者： ; ;

机构地区： 安徽医科大学

出　　处： 《中国临床药理学与治疗学》 2020年第6期610-617,共8页

摘　　要： 目的:研究阿霉素肾病大鼠模型的建立及地塞米松植入剂通过肾囊植入的保护作用及其可能的作用机制。方法:大鼠尾静脉注射阿霉素4mg/kg,隔周后再次注射阿霉素3.5 mg/kg建立肾脏损伤模型。造模成功后,模型组进行肾囊穿刺,辅料对照组肾囊内注射不含药的辅料(1.4 mg/kg),实验组肾囊内一次性注射给药(2.8,1.4,0.7 mg/kg),阳性药组灌胃给药8周(0.1 mg/kg)。造模前后定期检测体质量、肾功能和血液生化指标,实验结束后用碘酸雪夫(periodic-acid schiff,PAS)、天狼猩红(sirius red,SR)、免疫组织化学法(immunohistochemistry,IHC)观察肾小球系膜基底膜、肾组织胶原纤维、足细胞和裂孔隔膜中相关蛋白Podocin和CD2相关蛋白(CD2AP)蛋白表达变化。结果:阿霉素大鼠血蛋白含量降低,血总胆固醇、尿酸、血肌酐和尿素氮升高(P<0.05或P<0.01),肾小球系膜和纤维增多。肾组织Podocin蛋白表达减少,CD2AP蛋白表达增多(P<0.05或P<0.01)。地塞米松植入剂可以增加阿霉素大鼠体质量和血蛋白水平,降低血脂和血尿酸水平(P<0.05或P<0.01),改善肾功能和组织的损伤,调节Podocin和CD2AP蛋白的异常表达和分布(P<0.05或P<0.01)。结论:尾静脉分次注射阿霉素方法可以建立稳定肾病模型;地塞米松植入剂肾囊植入可以改善阿霉素肾病损伤,其机制可能是调节Podocin和CD2AP蛋白的表达与分布,加强足细胞屏障滤过功能。 AIM:To study the establishment of adriamycin nephropathy rat model and the protective effects and mechanisms of dexamethasone implants(DEXI)through renal capsule implantation.METHODS:The adriamycin-induced nephropathy model was built by injecting Adriamycin(4 mg/kg)and Adriamycin(3.5 mg/kg)was injected again after week into tail-vein in SD rats.Renal capsule puncture was performed in model group.The excipient control group injected intra-renal capsule with drug-free excipient(1.4 mg/kg).The experimental group(2.8,1.4,0.7 mg/kg)was given by intrarenal capsule injection and positive drug group(0.1 mg/kg,qd×8 w)was made by intragastric administration.The rat weight,kidney function and blood biochemical were observed and detected during the experiment.After the experiment,rat kidneys were stained with periodic acid-schiff to observe the morphological changes of mesangial and basement and sirius red to observe the renal tissue collagen fibers,expression of podocin and CD2AP were detected by immunohistochemistry.RESULTS:The blood protein content of adriamycin rats decreased,total blood cholesterol,uric acid,blood creatinine and urea nitrogen increased(P<0.05 or P<0.01),mesangium and fibers increased.The expression of Podocin protein in kidney tissue decreased and the expression of CD2AP protein increased(P<0.05 or P<0.01).DEXI increased the weight and blood protein levels of adriamycin rats,reduced blood lipids and blood uric acid levels(P<0.05 or P<0.01),improved renal function and tissue damage,and regulated the abnormal expression and distribution of Podocin and CD2AP proteins(P<0.05 or P<0.01).CONCLUSION:These results suggest that injecting adriamycin into the tail vein can establish a stable kidney disease model.DEXI renal capsule implantation can improve adriamycin nephropathy injury,and its mechanism may be related to restoration the expression and distribution of Podocin and CD2AP proteins on podocyte slit diaphragm.

关 键 词： 地塞米松植入剂 肾囊植入 足细胞 裂孔隔膜

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