论文部分内容阅读
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。
Objective To investigate the effect of protein kinase A (PKA) in vivo on loss of podocyte and proteinuria in adriamycin-induced nephropathy mice. Methods · BALB / c male mice aged 6 to 8 weeks were divided into 3 groups: ADR group received ADR 10 mg / kg tail vein injection to construct ADR nephropathy mouse model, AD group rats were given PKA signal stimulation Agent p CPT-c AMP 50 mg / (kg · d) intraperitoneal injection, the control group without any intervention. Protein electrophoresis + Coomassie blue staining were used to observe the changes of urinary albumin. WT-1 immunohistochemical staining was used to observe the number of podocytes. Immunofluorescence double staining was used to observe the podocyte injury. Results Compared with the control group, the urinary albumin / creatinine ratio was significantly increased in ADR nephropathy mice, the number of glomerular podocytes was significantly decreased, the expressions of podocalyxin and podocyte specific proteins were significantly decreased, and the degeneration of podocytes was impaired Increased expression of protein desmin. p The ratio of albumin / creatinine in ADR mice was decreased after CPT-c AMP intervention. The expression of WT-1 positive cells, synaptopodin and podocalyxin increased, and the expression of desmin decreased. CONCLUSION • p CPT-c AMP activates PKA signaling to reduce podocyte injury in ADR nephropathy mice and prevent podocyte depletion and proteinuria. Its role may be associated with p CPT-c AMP prevent ADR nephropathy mouse podocyte dysfunction.