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激活蛋白激酶A信号对阿霉素肾病小鼠足细胞失分化的影响

发布时间:2019-07-05 06:46
【摘要】:目的·探讨体内激活蛋白激酶A(PKA)对阿霉素(ADR)肾病小鼠足细胞失分化以及蛋白尿的作用。方法·选择6~8周龄BALB/c雄性小鼠分为3组:ADR组予以ADR 10 mg/kg尾静脉注射构建ADR肾病小鼠模型,A+P组为ADR肾病小鼠予PKA信号激动剂p CPT-c AMP 50 mg/(kg·d)腹腔注射,对照组不做任何干预。蛋白电泳+考马斯蓝染色方法观察小鼠尿白蛋白变化,WT-1免疫组化染色观察足细胞数量,免疫荧光双染观察足细胞的损伤。结果·与对照组相比,ADR肾病小鼠尿白蛋白/肌酐比值显著升高,肾小球足细胞数量显著降低,足细胞特异性蛋白synaptopodin和podocalyxin表达明显下降,足细胞受损伤失分化标志蛋白desmin表达增多。p CPT-c AMP干预后ADR小鼠白蛋白/肌酐比值降低,WT-1阳性细胞和synaptopodin和podocalyxin表达增多,desmin表达减少。结论·p CPT-c AMP激活PKA信号后可减轻ADR肾病小鼠足细胞损伤,防止足细胞数量减少,减轻蛋白尿。其作用可能与p CPT-c AMP防止ADR肾病小鼠足细胞失分化相关。
[Abstract]:Objective to investigate the effect of activated protein kinase A (PKA) on podocyte dedifferentiation and proteuria in mice with doxorubicin (ADR) nephropathy. Methods male BALB/c mice aged 6 to 8 weeks were divided into three groups: ADR group was treated with ADR 10 mg/kg tail vein injection to establish ADR nephropathy model mice, A P group was treated with PKA signal agonist p CPT-c AMP 50 mg/ (kg 路d) intraabdominal injection, and the control group did not do any intervention. The changes of urinary albumin in mice were observed by protein electrophoresis Coomassie blue staining, the number of podocytes was observed by WT-1 immunohistochemical staining, and the damage of podocytes was observed by immunofluorescence double staining. Results compared with the control group, the ratio of urinary albumin / creatine in ADR nephropathy mice was significantly increased, the number of bulbar podocytes was significantly decreased, the expression of podocyte specific protein synaptopodin and podocalyxin was significantly decreased, and the expression of dedifferentiated marker protein desmin in podocytes was increased. After p CPT-c AMP intervention, the ratio of albumin / creatine decreased, the expression of WT-1 positive cells and synaptopodin and podocalyxin increased, and the expression of desmin decreased. Conclusion the activation of PKA signal by p CPT-c AMP can alleviate the injury of podocytes, prevent the decrease of podocyte number and reduce proteuria in mice with ADR nephropathy. The effect of p CPT-c AMP may be related to the prevention of podocyte dedifferentiation in ADR nephropathy mice.
【作者单位】: 上海交通大学医学院附属仁济医院肾脏科;新疆维吾尔自治区喀什地区第二人民医院肾病科;
【基金】:新疆维吾尔自治区自然科学基金(2015211C222)~~
【分类号】:R692

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