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Toll样受体4信号通路在心肌微血管内皮细胞缺氧复氧损伤中的变化

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2010年第4期
页码:
496-499
栏目:
基础研究
出版日期:
2010-06-10

文章信息/Info

Title:
Alteration of Toll-like receptor 4 pathway expression in cardiac microvascular endothelial cells during hypoxia-reoxygenation injury
作者:
张铮; 王亚斌; 孙冬冬; 周萱; 张荣庆; 曹丰; 王海昌
第四军医大学西京医院心血管内科，陕西 西安 710032
Author(s):
ZHANG Zheng;  WANG Ya-bin;  SUN Dong-dong;  ZHOU Xuan;  ZHANG Yong-qing;  CAO Feng;  WANG Hai-chang
Department of Cardiovascular Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China
关键词:
Toll样受体-4; 心脏微血管内皮细胞; 缺氧-复氧损伤; 大鼠
Keywords:
TLR-4;  cardiac microvascular endothelial cells;  hypoxia-reoxygenation injury
分类号:
R392.12
DOI:
-
文献标识码:
A
摘要:
目的: 探讨Toll样受体4（TLR-4）信号通路在心肌微血管内皮细胞（CMECs）缺氧-复氧 (H-R)损伤过程中表达的变化。方法: 采用体外培养的CMECs，分为正常组、H-R组，其中H-R组根据复氧时间又分为复氧2 h、12 h及24 h组，用四甲基偶氮唑蓝(MTT)比色法检测内皮细胞增殖的能力。取细胞上清液用ELISA法检测白介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的水平；用Western blot法检测各组细胞中TLR-4及核因子-κB（NF-κB）表达的水平。结果: 与正常对照组相比，缺氧6 h复氧2 h、12 h、24 h后CMECs增殖分别降低48.6%（P<0.01）、49.1%（P<0.01）、63.2%（P<0.01）；TLR-4蛋白水平在复氧2 h以及12 h后明显升高(P<0.05)，24 h基本恢复正常；NF-κB表达水平在复氧2 h、24 h显著高于对照组(P<0.05)；而CMECs复氧2 h、12 h、24 h后分泌的IL-6、TNF-α水平均高于对照组(P<0.05)。结论: 在CMECs H-R损伤中，TLR-4及下游NF-κB的表达增加，炎性因子IL-6和TNF-α的分泌增加，说明H-R损伤可激活CMECs表面的TLR-4信号通路，这一过程可能参与了H-R诱导的CMECs损伤。
Abstract:
AIM:To detect the alteration of Toll-like receptor 4 (TLR-4) pathway expression in cardiac microvascular endothelial cells (CMECs) during hypoxia-reoxygenation (H-R) injury. METHODS: CMECs isolated from the hearts of adult rats were exposed to hypoxia (94% N2, 5% CO2, 1% O2) for 6 h followed by 2, 12 or 24 h reoxygenation (95% air, 5% CO2). Proliferation of CMECs was assessed by MTT assay, TLR-4 and NF-κB expressions were analyzed by Western blot and levels of IL-6 and TNF-α were detected by ELISA kits. RESULTS: The proliferation ability of CMECs was significantly inhibited by H-R injury (P<0.01) and H-R injury increased the TLR-4 expression 2 and 12 h after reoxygenation (P<0.05). The level of NF-κB increased 2 and 24 h after reoxygenation (P<0.05) and H-R injury enhanced IL-6 and TNF-α secretion compared with those in control groups (P<0.05). CONCLUSION: H-R injury increases the TLR-4 and NF-κB expressions in CMECs and enhances secretion of IL-6 and TNF-α. Activation of TLR-4/NF-κB pathway may participate in H-R injury of CMECs.

参考文献/References

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备注/Memo

备注/Memo:
收稿日期：2009-07-24.通讯作者：王海昌，教授，主要从事冠心病机制与治疗的研究Email:wanghc@fmmu.edu.cn 共同通讯作者：曹丰，教授，主要从事分子影像及干细胞治疗的研究Email：wind8828@gmail.com 作者简介：张铮，硕士生Email:faithword@yahoo.cn
更新日期/Last Update: 2010-05-20