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脂联素通过APPL1减轻缺氧/复氧损伤诱导的心肌细胞凋亡(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2012年第3期
页码:
287-291
栏目:
基础研究
出版日期:
2012-06-25

文章信息/Info

Title:
Adiponectin protects cardiomyocytes from hypoxia/reoxygenation-induced apoptosis via upregulation of APPL1
作者:
李冬冬; 张海锋; 孙 璐; 张荣庆; 王海昌; 陶 凌
(第四军医大学西京医院心血管内科，陕西 西安 710032)
Author(s):
LI Dong-dong;  ZHANG Hai-feng;  SUN Lu;  ZHANG Rong-qing;  WANG Hai-chang;  TAO Ling
(Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)
关键词:
脂联素; APPL1; 心肌细胞; 缺氧/复氧损伤; 乳鼠
Keywords:
adiponectin;  APPL1;  cardiomyocytes;  hypoxia/reoxygenation;  apoptosis
分类号:
R589.2
DOI:
-
文献标识码:
A
摘要:
目的:探讨APPL1在脂联素（adiponectin，ANP）拮抗SD乳鼠心肌细胞（neonatal cardiomyocytes）缺氧/复氧（H/R）损伤中的作用。方法： 分离SD乳鼠心肌细胞并培养。通过对培养的心肌细胞H/R损伤模拟缺血/再灌注（simulated ischemia reperfusion，SI/R）后，随机分为对照组、H/R组、H/R+APN组及H/R+APN+APPL1 RNAi组。采用四甲基偶氮唑蓝(MTT)比色法检测细胞的生存率，原位缺口末端标记(TUNEL)法检测细胞的凋亡，Western blot检测APPL1蛋白的表达。结果： 与对照组相比，H/R组吸光度值明显降低（P<0.01），凋亡指数(AI)显著上升（P<0.01）。与对照组和H/R组相比，H/R+APN组中APPL1的表达明显上升（P<0.05）。以RNAi抑制APPL1表达后，与H/R+APN组相比，H/R+APN+APPL1 RNAi组凋亡指数率(%)明显上升 ［(28.32±4.13)% vs.(9.78±2.16)%，P<0.01］。结论： APN可显著抑制H/R损伤诱导的心肌细胞凋亡，促进心肌细胞存活，其拮抗作用与上调APPL1蛋白的表达相关。
Abstract:
AIM:To investigate the role of APPL1 on the protective effect of adiponectin on neonatal cardiomyocytes subjected to hypoxia-reoxygenation (H/R). METHODS: Primary neonatal cardiomyocytes were isolated from the ventricles of 2- to 3-day-old Sprague Dawley (SD) rats by enzymatic digestion and were exposed to hypoxia (940 ml/L N2, 50 ml/L CO2, 10 ml/L O2) for 6 h followed by 12 h reoxygenation (950 ml/L air, 50 ml/L CO2). Cell viability of neonatal cardiomyocytes was measured by MTT assay. Apoptosis of neonatal cardiomyocytes was detected by TUNEL and expression of APPL1 protein was analyzed by Western blot. RESULTS: Cardiomyocyte viability was reduced after H/R (P<0.01 vs. control) and the apoptosis index increased compared with the control group (P<0.01). Administration of adiponectin during reperfusion dramatically attenuated the viability and apoptosis of neonatal cardiomyocytes and upregulated APPL1 expression. To further ascertain the role of APPL1 in adiponectin-induced cardioprotective effect, neonatal cardiomyocytes were transfected with siRNA targeting APPL1, which significantly blunted the anti-apoptotic effect of adiponectin. CONCLUSION: Adiponectin exerts a protective effect on neonatal cardiomyocytes against H/R injury through upregulating APPL1 expression.

参考文献/References

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备注/Memo

备注/Memo:
收稿日期：2011-12-02.基金项目：国家自然科学基金资助（2009AA02Z104） 通讯作者：陶凌，主任医师，主要从事糖尿病与心血管保护研究 Email:lingtao2006@gmail.com 共同通讯作者：王海昌，主任医师，主要从事冠心病研究 Email:wanghc@fmmu.edu.cn 作者简介：李冬冬，硕士生 Email: dongdongli778@ gmail.com
更新日期/Last Update: 2012-05-02