PPAR-α激动剂对PAN诱导肾小球足细胞损伤的保护作用  

Protective effect of PPAR-α agonist on PAN-induced podocyte injury

作　　者：许俊铭[1] 潘方瑜 刘源[1] 岳晓阳[1] 邹军[1] 

机构地区：[1]厦门大学基础医学系,福建厦门361102 [2]重庆医科大学附属第一医院,重庆404100

出　　处：《中国药理学通报》2014年第10期1377-1382,共6页Chinese Pharmacological Bulletin

基　　金：福建省自然科学基金资助项目(No 2013J01357)

摘　　要：目的探讨PPAR-α激动剂非诺贝特对氨基核苷嘌呤霉素(PAN)诱导肾小球足细胞损伤的作用及其机制。方法将18只8周龄SD♀大鼠随机分为3组(n=6)。PAN模型组和非诺贝特组1次尾静脉注射PAN 65 g·g-1,空白对照组注射生理盐水,PAN注射后d1,非诺贝特组灌胃非诺贝特40 mg·kg-1·d-1),空白对照组和PAN模型组灌胃等体积溶剂。分别于d 0、6、10收集24 h尿样,采用Bradford法测定大鼠24 h尿蛋白含量。PAN注射后10 d将大鼠安乐死,收集肾小球样本。利用Western blot和Real-Time PCR检测肾小球足细胞损伤标记物的表达和凋亡相关基因、骨架蛋白以及裂隙膜蛋白基因转录活性。结果注射PAN后d10,24 h尿蛋白含量较d 0明显上升,足细胞损伤标记物desmin基因水平和蛋白表达明显增加,线粒体凋亡通路、TGF-β/Smad通路和p38通路转录水平明显上调,足细胞骨架蛋白和裂隙膜蛋白的转录活性明显增加。非诺贝特处理能够明显降低PAN引起的尿蛋白,改善PAN对足细胞的损伤作用;明显抑制凋亡通路的转录活性;降低骨架蛋白和裂隙膜蛋白的转录活性。结论非诺贝特能够改善PAN诱导的肾小球足细胞损伤,其作用机制与抑制凋亡通路有关。Aim To investigate the function of fenofi-brate on PAN （ puromycin aminonucleoside ）-induced podocyte injury. Methods SD female rats of 18-week-old were randomly assigned into 3 groups （ n =6 ） . Mice in PAN group and fenofibrate treated groupreceived a single intravenous injection of PAN （ 65 mg ·kg-1 ） , while those in control group received equal volume of saline. Mice in fenofibrate treated group re-ceived 40 mg · kg-1 · d-1 of fenofibrate （ intragastric administration ） on day 1 after PAN injection , whilethose in PAN group and control group received equal volume of vehicle. 24 hours urine samples from all group were collected on day 0（1 day before PAN injec-tion）, day 6, day 10. The 24 hours urine protein was detected by Bradford assay. All the rats were sacrificed 10 days after the induction of podocyte injury, and glo-merulus sample were collected. The expression of podocyte injury marker and transcription level in apop-tosis, podocyte cytoskeleton protein, slit diaphragm protein were evaluated by Western blot and real-time PCR. Results Compared with the control group, 10 days after injection of PAN, 24 hours urine protein was obviously increased, and the expression and transcrip-tion level of podocyte injury marker desmin, apoptosis, podocyte cytoskeleton protein, slit diaphragm protein were upregulated greatly, however, those were signifi-cantly lower in fenofibrate treated group as compared with those in PAN group. Conclusions PPAR-α ago-nist fenofibrate can ameliorate PAN-induced glomerulus podocyte injury, and the mechanism involved may be associated with inhibition of the mitochondria apopto-sis, TGF-β/Smad pathway and p38 pathway.

关 键 词：PAN 足细胞损伤 PPAR-Α 非诺贝特 足细胞结构蛋白 凋亡通路 

分 类 号：R-332[医药卫生] R322.61