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DIDS对I/RI心肌组织中信号分子PI3K/Akt及ROS的调控(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2011年第4期
页码:
429
栏目:
基础研究
出版日期:
2011-08-25

文章信息/Info

Title:
Regulation of DIDS on PI3K/Akt and ROS signal transduction in ischemia-reperfusion myocardial injury
作者:
刘佳妮; 刘艳霞; 沈明志; 赵萌; 翟雅莉; 丁铭格; 王晓明
第四军医大学西京医院老年病科，陕西 西安 710032
Author(s):
LIU Jia-ni;  LIU Yan-xia;  SHEN Ming-zhi;  ZHAO Meng;  ZHAI Ya-li;  DING Ming-ge;  WANG Xiao-ming
Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China
关键词:
DIDS; 氯离子通道;  缺血/再灌注损伤; 活性氧簇; 磷脂酰肌醇-3激酶/蛋白激酶B; 大鼠
Keywords:
DIDS;  chloride channel;  ischemia-reperfusion injury;  ROS;  PI3K/Akt
分类号:
R542.2
DOI:
61-1268/R.20110503.1150.004
文献标识码:
A
摘要:
目的:探讨氯离子通道阻断剂4,4-二异硫氰基芪-2,2′-二磺酸（4,4′-Diisothiocyanostilbene-2,2′-disulfonic acid，DIDS）对缺血/再灌注损伤(Ischemia/reperfusion injury，I/RI)心肌组织中信号分子磷脂酰肌醇-3激酶（Phosphoinositide-3 kinase，PI3K）/蛋白激酶B（Protein kinase B,Akt）及活性氧（ROS）的调控。方法： 常规建立SD大鼠I/RI心脏模型，32只，随机分成4组（n=8），分为假手术组、I/R组、过氧化氢酶(CAT)组及DIDS组。伊文思蓝和红四氮唑（TTC）双染色法检测大鼠心肌梗死面积、荧光分光光度计法检测心肌组织中ROS的含量、用western blot 蛋白印迹法检测Akt和p-Akt的水平，TUNNEL法检测心肌细胞凋亡，以及检测血清肌酸激酶（CK）、乳酸脱氢酶（LDH）、超氧化物歧化酶(SOD)的活性及丙二醛（MDA）的含量。结果： ①与I/R组对比，DIDS组和CAT两组的心肌梗死面积、细胞凋亡数、血清CK、LDH的活性均明显减少（P<0.05）；但DIDS和CAT二组间无差异。②与I/R组对比，DIDS组和CAT组血清中MDA的含量明显减小；而SOD的活性明显升高（P<0.05）；与DIDS组比较，CAT组SOD的活性明显升高（P<0.05）、MDA的含量明显减少（P<0.05）。③与I/R组对比，CAT组和DIDS组心肌组织中ROS的含量显著降低（P<0.05）；CAT组较DIDS组降低的更明显（P<0.05）。④各组心肌组织中总Akt的表达无显著差异。与假手术组相比，I/R、DIDS 和CAT 3组p-Akt的水平均有明显升高（P<0.05）；DIDS组p-Akt的水平显著高于I/R和CAT组（P<0.05）；但I/R和CAT两组间无差异。结论： DIDS同时具有激活PI3K/Akt信号通路及降低ROS水平，减轻I/RI，达到保护心肌组织的作用。
Abstract:
AIM:To investigate the regulation of DIDS on PI3K/Akt and ROS signal transduction in ischemia-reperfusion myocardial injury. METHODS: Male SD rats were randomized into four groups: sham group, I/RI (ischemia/reperfusion injury) group, CAT (catalase) group and DIDS group. Myocardial infarction size, levels of tissue ROS, myocardial apoptosis index, serum levels of creatine kinase (CK), lacate dehydrogenase (LDH), malondialdehyde (MDA) and superoxide dismutase (SOD), and the myocardial Akt and phospho-Akt protein activity of MDA and SOD, and the myocardial Akt and activity of expressions were determined. RESULTS: Compared with those in I/RI group, myocardial infarction size, apoptotic index and activity of CK and LDH significantly decreased in DIDS and CAT groups. No difference was seen between CAT group and DIDS group. Compared with those in I/RI group, MDA levels decreased and the activity of SOD increased in DIDS and CAT groups (P<0.05). The activity of SOD was higher, but the levels of MDA were lower in CAT group compared with those in DIDS group (P<0.05). Compared with those in I/RI group, the myocardial ROS levels significantly reduced in DIDS and CAT groups. ROS levels in CAT group were lower than those in DIDS group (P<0.05). No significant difference on the total Akt expression was observed among the four groups (P>0.05). Compared with those in the sham group, phospho-Akt levels were enhanced in the other three groups (P<0.05). Phospho-Akt levels were significantly higher in DIDS group compared with those in I/RI and CAT groups (P<0.05), but no significant difference was observed in the levels of phospho-Akt between I/RI group and CAT group. CONCLUSION: DIDS strongly protects cardiomyocytes against I/RI-induced apoptosis via activating PI3K/Akt signaling pathway and reducing ROS levels.

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备注/Memo

备注/Memo:
收稿日期：2010-10-27.基金项目：国家自然基金课题项目资助（30770847，81070127） 通讯作者：王晓明，教授，主要从事心血管疾病的基础与临床研究Email:xmwang@fmmu.edu.cn 作者简介：刘佳妮，医师，硕士生Email:liujiani99@sohu.com
更新日期/Last Update: 2011-06-02