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Sorafenib通过抑制TGF-β/Smad途径延缓肾纤维化的研究
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Sorafenib通过抑制TGF-β/Smad途径延缓肾纤维化的研究
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Sorafenib通过抑制TGF-β/Smad途径延缓肾纤维化的研究
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Journal Article
Sorafenib通过抑制TGF-β/Smad途径延缓肾纤维化的研究
2016
Overview
目的探讨sorafenib减轻肾纤维化的作用及机制。方法用低、中、高剂量sorafenib分别给单侧输尿管梗阻（UUO）模型大鼠灌胃或干预经TGF-β1刺激的NRK-52E细胞。HE染色观察各组肾组织纤维化情况,免疫荧光染色检测肾组织及NRK-52E细胞α-SMA、E-cadherin的表达情况。用流式细胞术测定各组NRK-52E细胞周期。Western blot检测各组NRK-52E细胞中Smad3和p-Smad3的表达变化。结果 HE染色结果显示,与UUO模型组相比,sorafenib治疗组肾间质纤维化明显减轻,小管萎缩、炎细胞浸润较轻（P〈0.05）;与对照组比较,sorafenib治疗组E-cadherin在NRK-52E细胞和肾组织中表达均增加,而α-SMA表达均降低（P〈0.05）;流式细胞术分析发现细胞周期停滞于G0/G1期的细胞数明显增加,而进入G2、S期的细胞数明显减少（P〈0.05）;与对照组比较,sorafenib干预组p-Smad3蛋白在NRK-52E细胞中表达降低,且与sorafenib剂量呈正相关（P〈0.05）。结论 sorafenib具有抗肾脏纤维化作用,主要通过TGF-β/Smad途径发挥作用,可能为治疗肾纤维化提供一种早期干预的新手段。
Publisher
西安交通大学第二附属医院肾病科,陕西西安,710004%延安大学附属医院消化内科,陕西延安,716000
Subject
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