锰苯甲酸卟啉在嘌呤霉素氨基核苷诱导的大鼠肾脏病模型中的作用  

Effects of Mn TBAP on puromycin aminonucleoside induced nephrotic rats

作　　者：宋瑞花 白咪 张园园[1] 林加娟[1] 丁桂霞[1] 黄松明[1] 张爱华[1] Song Ruihua Bai Mi Zhang Yuanyuan Lin Jiajuan Ding Guixia Huang Songming Zhang Aihua(Departmen of Nephrology, Nanjing Children＇ s Hospital Affiliated to NJMU, Nanjing 210008, China)

机构地区：[1]南京医科大学附属儿童医院肾脏科,江苏南京210008

出　　处：《南京医科大学学报（自然科学版）》2016年第11期1321-1325,共5页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家973项目(2013CB530604)

摘　　要：目的 :探讨超氧化物歧化酶类似物锰苯甲酸卟啉(Mn TBAP)在嘌呤霉素氨基核苷(puromycin aminonucleoside,PAN)诱导的大鼠肾脏病模型中的作用。方法:24只雄性SD大鼠按照每组8只随机分为正常对照组、模型组(一次性尾静脉注射150 mg/kg PAN建立PAN诱导的大鼠肾脏病模型)、Mn TBAP治疗组[造模大鼠于造模当天开始腹腔注射Mn TBAP 10 mg/(kg·d),共给药14 d]。收集大鼠24 h尿液,Bradford法检测24 h尿蛋白总量;应用透射电镜观察肾小球足细胞的超微结构;实时荧光定量PCR法在m RNA水平检测足细胞裂孔隔膜蛋白Nephrin和Podocin的表达量;Western blot在蛋白质水平检测Nephrin和Podocin的表达量。结果 :1与正常对照组相比,模型组大鼠的24 h尿蛋白总量明显升高(P<0.01),肾脏指数升高(P<0.01);Mn TBAP治疗后大鼠24 h尿蛋白总量较模型组下降(P<0.01),肾脏指数较模型组下降(P<0.01);2透射电镜观察结果表明,模型组大鼠的肾小球足细胞足突出现广泛融合甚至消失,Mn TBAP治疗后这种现象得以改善;3实时荧光定量PCR结果显示,模型组大鼠肾皮质Nephrin和Podocin的m RNA表达较正常对照组降低(P<0.01),Mn TBAP治疗组Nephrin和Podocin的m RNA表达较模型组增加(P<0.01);4Western blot结果显示,模型组大鼠肾皮质Nephrin和Podocin蛋白的表达较正常对照组降低(P<0.01),Mn TBAP治疗组Nephrin和Podocin蛋白的表达较模型组增加(P<0.01)。结论:Mn TBAP可以降低PAN诱导的肾病大鼠的蛋白尿,并明显减轻足细胞损伤。Objective：To explore the effects of Mn TBAP on puromycin aminonucleoside（PAN）-induced nephrotic rats. Methods：A total of 24 male Sprague-Dawley（SD）rats were randomly divided into the following groups（n=8 for each group）：the control group,the PAN group（one single dose-150 mg/kg of PAN was injected into rats by tail-vein injection）and the Mn TBAP-treated group [on the day with injection of PAN,the rats were treated with a daily intraperitoneal injection of 10 mg/（kg·d） Mn TBAP for 14 days].Twenty-four hours urinary protein excretion was detected by the Bradford protein assay. The ultrastructure of glomerular potocyte was observed by the transmission electron microscope. Nephrin and podocin expression levels were measured by real-time PCR and Western blot. Results： ①24 hours urinary protein excretion and the renal index of PAN group were significantly increased compared to those of the control group（P〈0.01）,while the 24 h urinary protein and renal index of the Mn TBAP-treated group was lower than those of the PAN group（P〈0.01）. ②The transmission electron microscope results showed that glomerular podocyte in the PAN group fused and disappeared widely,but it markedly alleviated after Mn TBAP treatment. ③Real-time PCR showed that the expression of nephrin and podocin in the PAN group were reduced in comparison to those of the control group（P〈0.01）,which was restored by Mn TBAP treatment（P〈0.01）;④ Western blot showed that the expressions of nephrin and podocin in the PAN group were reduced in comparison to those of the control group（P〈0.01）,which was restored by Mn TBAP treatment（P〈0.01）. Conclusion：Mn TBAP could decrease urinary protein and podocyte injury in PAN-induced nephrotic rats.

关 键 词：锰苯甲酸卟啉 嘌呤霉素氨基核苷 足细胞 

分 类 号：R692.31[医药卫生—泌尿科学]