【摘要】：目的·探討體內(nèi)激活蛋白激酶A(PKA)對(duì)阿霉素(ADR)腎病小鼠足細(xì)胞失分化以及蛋白尿的作用。方法·選擇6~8周齡BALB/c雄性小鼠分為3組:ADR組予以ADR 10 mg/kg尾靜脈注射構(gòu)建ADR腎病小鼠模型,A+P組為ADR腎病小鼠予PKA信號(hào)激動(dòng)劑p CPT-c AMP 50 mg/(kg·d)腹腔注射,對(duì)照組不做任何干預(yù)。蛋白電泳+考馬斯藍(lán)染色方法觀察小鼠尿白蛋白變化,WT-1免疫組化染色觀察足細(xì)胞數(shù)量,免疫熒光雙染觀察足細(xì)胞的損傷。結(jié)果·與對(duì)照組相比,ADR腎病小鼠尿白蛋白/肌酐比值顯著升高,腎小球足細(xì)胞數(shù)量顯著降低,足細(xì)胞特異性蛋白synaptopodin和podocalyxin表達(dá)明顯下降,足細(xì)胞受損傷失分化標(biāo)志蛋白desmin表達(dá)增多。p CPT-c AMP干預(yù)后ADR小鼠白蛋白/肌酐比值降低,WT-1陽性細(xì)胞和synaptopodin和podocalyxin表達(dá)增多,desmin表達(dá)減少。結(jié)論·p CPT-c AMP激活PKA信號(hào)后可減輕ADR腎病小鼠足細(xì)胞損傷,防止足細(xì)胞數(shù)量減少,減輕蛋白尿。其作用可能與p CPT-c AMP防止ADR腎病小鼠足細(xì)胞失分化相關(guān)。
[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.
【作者單位】： 上海交通大學(xué)醫(yī)學(xué)院附屬仁濟(jì)醫(yī)院腎臟科;新疆維吾爾自治區(qū)喀什地區(qū)第二人民醫(yī)院腎病科;
【基金】：新疆維吾爾自治區(qū)自然科學(xué)基金(2015211C222)~~
【分類號(hào)】：R692

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