>
网站首页期刊介绍通知公告编 委 会投稿须知电子期刊广告合作联系我们
最新消息:
丹参酮Ⅰ在肾脏缺血再灌注损伤中的保护作用研究
作者:高文强1 2  邱雪峰1  李凯1  陈蔚1  赵晓智1  李笑弓1 2  郭宏骞1 
单位:1. 南京大学医学院附属鼓楼医院 泌尿外科, 江苏 南京 210008;
2. 东南大学 医学院, 江苏 南京 210009
关键词:肾脏 缺血再灌注 急性肾损伤 氧化应激 丹参酮Ⅰ 
分类号:R-33;R965
出版年·卷·期(页码):2018·37·第三期(372-379)
摘要:

目的:探讨丹参酮Ⅰ(T-Ⅰ)在肾脏缺血再灌注损伤(RIRI)中的保护作用。方法:(1)体内实验:将雄性ICR小鼠随机分为假手术(sham)组、sham+T-Ⅰ组、缺血再灌注(IR)组、IR+T-Ⅰ组4组,术前每组腹腔注射等量T-Ⅰ或玉米油2周,左肾蒂夹闭50 min诱导RIRI,收集术后48 h血清及肾脏标本,比较各组之间的血清肌酐(Cr)水平、尿素氮(BUN)水平、肾脏组织病理学评分、肾脏组织凋亡比例及肾脏组织内超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量。(2)体外实验:用过氧化氢处理人肾小管上皮细胞(HK-2)建立氧化应激模型,将HK-2分为对照(C)组、T-Ⅰ组、H2O2组、H2O2+T-Ⅰ组4组;用T-Ⅰ或其溶剂处理24 h,然后用过氧化氢处理2 h,比较各组细胞活力、细胞凋亡及细胞内活性氧水平。结果:(1)体内实验:与IR组相比,IR+T-Ⅰ组血清Cr、BUN水平显著降低,肾组织内SOD活力升高而MDA含量显著下降,肾脏组织凋亡比例显著降低,且IR+T-Ⅰ组肾脏组织学病理评分较IR组显著降低;(2)体外实验:经过T-Ⅰ预处理,可以显著降低过氧化氢处理后的细胞内活性氧水平,增强细胞活力,减少细胞凋亡。结论:T-Ⅰ通过抗氧化活性在RIRI中起到保护作用。

Objective: To investigate the protective effect of Tanshinone Ⅰ(T-Ⅰ) on renal ischemia/reperfusion injury(RIRI).Methods: (1) In vivo study:the male ICR mice were divided into 4 groups:sham group, sham+T-Ⅰ group, IR group and IR+T-Ⅰ group. All the mice received T-Ⅰ or corn oil via intraperitoneal injection for 2 weeks before surgery. Left renal pedicle was clamped with vascular clamp for 50 min to induce ischemia reperfusion injury. Serum samples and kidney tissue were collected after 48 h. Blood ureanitrogen(BUN), creatinine(Cr), superoxideismutase(SOD), malondialdehyde(MDA) and kidney histopathology score were compared among the groups.(2) In vitro study:human tubular epithelial cells(HK-2) were treated with H2O2 to induce oxidative stress injury, and HK-2 were divided into 4 group,i.e., control(C) group, H2O2 group, T-Ⅰ group and H2O2+T-Ⅰ group. Control(C) group and H2O2 group were pretreated with solvent while T-Ⅰ group and H2O2+T-Ⅰ group were pretreated with T-Ⅰ for 24 h followed by exposure to H2O2 for another 2 h. Cell viability and reactive oxygen species were compared among all groups.Results: (1)In vivo study:serum BUN and Cr in IR+T-Ⅰ group were significantly decreased compared with those in the IR group. Level of SOD was significantly higher while level of MDA was significantly lower in IR+T-Ⅰ group compared with those in IR group; histological score in IR+T-Ⅰ group was significantly reduced compared with that in IR group. (2)In vitro study:T-Ⅰ attenuated hydrogen peroxide-induced viability decrease and apoptosis of HK-2 cells, in addition, T-Ⅰ reduced the generation of ROS induced by hydrogen peroxide in HK-2 cells.Conclusion: T-Ⅰ plays a protective role in renal ischemia-reperfusion injury via antioxidant activity.

参考文献:

[1] MOSLEMI F,TAHERI P,AZIMIPOOR M,et al.Effect of angiotensin Ⅱtype 1 receptor blockade on kidney ischemia/reperfusion; a gender-related difference[J].J Renal Inj Prev,2016,5(3):140-143.
[2] LUO L N,XIE Q,ZHANG X G,et al.Osthole decreases renal ischemia-reperfusion injury by suppressing JAK2/STAT3 signaling activation[J].Exp Ther Med,2016,12(4):2009-2014.
[3] XU Y M,DING G H,HUANG J,et al.Tanshinone ⅡA pretreatment attenuates ischemia/reperfusion-induced renal injury[J].Exp Ther Med,2016,12(4):2741-2746. a P<0.05图6各组间细胞凋亡情况A.各组间流式细胞仪检测结果;B.定量分析结果a P<0.05图7 T-Ⅰ缓解H2O2诱导的HK-2内氧化应激水平A.各组细胞内ROS水平;B.其荧光强度定量
[4] CARDEN D L,GRANGER D N.Pathophysiology of ischaemia-reperfusion injury[J].J Pathol,2000,190(3):255.
[5] ZHOU L,ZUO Z,CHOW M S.Danshen:an overview of its chemistry,pharmacology,pharmacokinetics,and clinical use[J].J Clin Pharmacol,2005,45(12):1345-1359.
[6] TIAN X H,WU J H.Tanshinone derivatives:a patent review (January 2006-September 2012)[J].Expert Opin Ther Pat,2013,23(1):19.
[7] de OLIVEIRA M R,SCHUCK P F,BOSCO S M D.Tanshinone Ⅰ induces mitochondrial protection through an Nrf2-dependent mechanism in paraquat-treated human neuroblastoma SH-SY5Y cells[J].Mol Neurobiol,2017,54(6):4597-4608.
[8] TAO S,ZHENG Y,LAU A,et al.Tanshinone Ⅰ activates the Nrf2-dependent antioxidant response and protects against As(Ⅲ)-induced lung inflammation in vitro and in vivo[J].Antioxid Redox Signal,2013,19(14):1647-1661.
[9] JING X,WEI X,REN M,et al.Neuroprotective effects of Tanshinone Ⅰ against 6-OHDA-induced oxidative stress in cellular and mouse model of Parkinson's disease through upregulating Nrf2[J].Neurochem Res,2016,41(4):779-786.
[10] CHEN Y T,YANG C C,ZHEN Y Y,et al.Cyclosporine-assisted adipose-derived mesenchymal stem cell therapy to mitigate acute kidney ischemia-reperfusion injury[J].Stem Cell Res Ther,2013,4(3):62.
[11] DONNAHOO K K,MELDRUM D R,SHENKAR R,et al.Early renal ischemia,with or without reperfusion,activates NFkappaB and increases TNF-alpha bioactivity in the kidney[J].J Urol,2000,163(4):1328-1332.
[12] STALLONE G,INFANTE B,GESUALDO L.Older donors and older recipients in kidney transplantation[J].J Nephrol,2010,23(Suppl 15):S98-103.
[13] KOSIERADZKI M,ROWINSKI W.Ischemia/reperfusion injury in kidney transplantation:mechanisms and prevention[J].Transplant Proc,2008,40(10):3279-3288.
[14] PERICO N,CATTANEO D,SAYEGH M H,et al.Delayed graft function in kidney transplantation[J].Lancet,2004,364(9447):1814-1827.
[15] DEVARAJAN P.Update on mechanisms of ischemic acute kidney injury[J].J Am Soc Nephrol,2006,17(6):1503-1520.
[16] QIU X F,FU K,ZHAO X Z,et al.Protective effects of astaxanthin against ischemia/reperfusion induced renal injury in mice[J].J Transl Med,2015,13:28.
[17] GUNAL O,AKTAN A O,YEGEN C,et al.Captopril prevents the oxidative damage to proteins after renal ischemia reperfusion injury:role of endothelin-1[J].Prostag Leukotr Ess,1997,56(1):23-27.
[18] ESREFOGLU M,TOK O E,AYDIN M S,et al.Effects of beta-glucan on protection of young and aged rats from renal ischemia and reperfusion injury[J].Bratisl Lek Listy,2016,117(9):530-538.
[19] LEE J C,PARK J H,PARK O K,et al.Neuroprotective effects of Tanshinone Ⅰ from Danshen extract in a mouse model of hypoxia-ischemia[J].Anat Cell Biol,2013,46(3):183.
[20] TAO S,JUSTINIANO R,ZHANG D D,et al.The Nrf2-inducers Tanshinone Ⅰ and dihydrotanshinone protect human skin cells and reconstructed human skin against solar simulated UV[J].Redox Biol,2013,1:532-541.

服务与反馈:
文章下载】【发表评论】【查看评论】【加入收藏
提示:您还未登录,请登录!点此登录
您是第 405380 位访问者


copyright ©《东南大学学报(医学版)》编辑部
联系电话:025-83272481 83272483
电子邮件:
bjb@pub.seu.edu.cn

苏ICP备09058364