西罗莫司对蛋白负荷肾病模型大鼠肾脏足细胞的影响

目的：观察西罗莫司对蛋白负荷肾病模型大鼠肾脏足细胞的影响及氯沙坦的保护作用,并探讨相关机制。方法：清洁级雌性Wistar大鼠36只随机分为空白对照组、模型组、西罗莫司组和联合用药组。采用向大鼠腹腔注射牛血清白蛋白（BSA）制备蛋白负荷肾病大鼠模型。西罗莫司组：在模型大鼠基础上给予西罗莫司;联合用药组：在模型大鼠基础上给予西罗莫司和氯沙坦。检测各组大鼠的尿指标变化,在电镜下观察肾组织的病理改变,并采用免疫组化检测肾小球足细胞损伤的标志——desmin蛋白的表达。结果：（1）实验第7天,模型组、西罗莫司组和联合用药组大鼠均出现明显蛋白尿。西罗莫司组和联合用药组大鼠24h尿蛋白量均较模型组尿蛋白量显著增多（P〈0.05）,但联合用药组大鼠24h尿蛋白量较西罗莫司组有明显缓解（P〈0.05）。实验第14天,西罗莫司组大鼠24h尿蛋白量仍明显高于模型组（P〈0.05）,而联合用药组与模型组间的24h尿蛋白量差异无统计学意义（P〉0.05）。（2）电镜结果：模型组肾小球毛细血管基底膜结构基本完整,无增厚,偶见电子致密物沉积,偶见足突局灶性融合;西罗莫司的肾小球足突融合多见,足细胞内可见较多电子致密物;联合用药组大鼠电镜下足细胞改变与西罗莫司组相似。（3）西罗莫司组和联合用药组大鼠肾小球desmin蛋白表达均明显高于模型组（P〈0.05）,虽联合用药组大鼠desmin阳性表达较西罗莫司组有不同程度地减少,但OD值差异无统计学意义（P〉0.05）。结论：西罗莫司会加重蛋白负荷肾病大鼠的蛋白尿水平,其机制可能损伤肾小球足细胞后导致肾小球滤过屏障的损伤有关。

Effects of Sirolimus on the Processes Foot in Rats with Protein Overload Nephropathy

Objective:To investigate the effect of sirolimus on rats with protein overload nephropathy and explore the protective mechanism of losartan.Methods:Proteinuria might develop in renal-transplanted recipients who had converted from treatment with calcineurin inhibitors to treatment with sirolimus,the mechanism of this occurrence was unknown.We hypothesized that the antiangiogenic properties of rapamycin might be responsible.Experimental models with protein overload nephropathy,induced by intraperiotoneal inje...