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吡非尼酮对单侧输尿管梗阻大鼠肾小管间质纤维化的影响

Effect of Pirfenidone on Tubulointerstitial Fibrosis in Rats with Unilateral Ureteral Obstruction

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【作者】 李娣昕曾红兵纪春阳梁萍萍位红兰

【Author】 LI Di-xin1,ZENG Hong-bing2,JI Chun-yang2,LIANG Ping-ping2,WEI Hong-lan2(1.Department of Nephrology,the Fifth People’s Hospital of Chengdu,611130,China;2.Department of Nephrology,Tongji Hospital Affiliated with Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China)

【机构】 成都市第五人民医院肾内科华中科技大学同济医学院附属同济医院肾内科

【摘要】 目地探讨吡非尼酮(PFD)对单侧输尿管梗阻(UUO)模型大鼠肾小管间质纤维化(TIF)的影响及其可能机制,为临床使用PFD防治肾脏纤维化提供理论依据。方法 SD大鼠35只,分为3组、假手术组7只,模型组14只,治疗组14只。治疗组给予PFD 250 mg.kg-1.d-1,疗程14 d。假手术组于手术后14 d处死,后两组于手术后7及14 d分两批处死。行过碘酸希夫染色(PAS)及Masson染色观察病理变化;原位末端标记法(TUNEL)观察肾小管上皮细胞(RTC)凋亡的情况;免疫组化法检测肾小管半胱氨酸天门冬氨酸蛋白酶(Caspase)-3的蛋白表达;比色法测定肾组织丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性。结果假手术组肾组织无明显病理改变;模型组TIF明显加重,RTC凋亡及Caspase-3表达增加(P<0.05),且14 d时较7 d时更明显,但治疗组以上指标明显改善(P<0.05);与假手术组比较,模型组MDA含量明显增加(7 d较14 d时更明显),SOD活性明显下降(14 d较7 d时更明显);但与模型组比较,治疗组MDA7 d时显著改善,14 d时差别不明显,SOD 7及14 d均明显改善,以14 d为甚。结论 PFD能明显减少UUO大鼠RTC的凋亡,从而改善TIF,上述作用可能与该药物抑制氧化应激和Caspase-3相关的凋亡途径有关。

【Abstract】 Objective To explore the effect of pirfenidone(PFD) on tubulointerstitial fibrosis(TIF) in rats with unilateral ureteral obstruction(UUO)and its possible mechanism. Methods Thirty-five female SD rats were randomly divided into three groups:(Ⅰ)sham-operated group(n=7),(Ⅱ)UUO model group(n=14),(Ⅲ) PFD group(n=14):rats underwent UUO and were treated with PFD 250 mg·kg-1·d-1for 14 days.Rats in group I were all sacrificed at day 14 after operation,those in group Ⅱ and Ⅲ were sacrificed at day 7 and 14,respectively.Renal tissues were examined by PAS and MASSON stain;TUNEL and immunohistochemistry were applied to determine the apoptosis and caspase-3 protein expression of renal tubular epithelial cells(RTC);the content of MDA and activity of SOD in renal cortex were assessed by chemical colorimetry. Results No pathology changes were found in group I;while compared with group I,the TIF,TUNEL-positive and caspase-3-positive cells all remarkably increased in group Ⅱ,especially at day 14,all of which were ameliorated in group Ⅲ(P<0.05).Compared with group I,the content of MDA was raised in group Ⅱ,especially at day 7,whereas activity of SOD declined,especiall at day 14;compared with group Ⅱ,MDA in group Ⅲ was decreased obviously at day 7,activity of SOD increased significantly,especiall at day 14. Conclusion PFD remarkably ameliorates tubulointerstitial fibrosis in UUO rats and improve TIF,which may be associated with reduction of oxidative stress and caspase-3 related apoptosis.

  • 【文献出处】 医药导报 ,Herald of Medicine , 编辑部邮箱 ,2011年06期
  • 【分类号】R96
  • 【被引频次】9
  • 【下载频次】151
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