2型糖尿病患者肿瘤坏死因子α及环氧合酶2组蛋白H3乙酰化研究  

Histone H3 acetylation of tumor necrosis factor-alpha and cyclooxygenase-2 in patients with type 2 diabetes

作　　者：侯粲[1] 赵明[2] 李霞[1] 李一君[1] 蔺怡[1] 陆前进[2] 周智广[1] 

机构地区：[1]中南大学湘雅二医院内分泌科糖尿病中心代谢内分泌研究所代谢综合征研究中心糖尿病免疫学教育部重点实验室,长沙410011 [2]中南大学湘雅二医院皮肤性病科,长沙410011

出　　处：《中华医学杂志》2011年第26期1805-1808,共4页National Medical Journal of China

基　　金：国家重点基础研究发展计划“973”项目（2009CB825605）;湖南省高校科技创新团队支持计划项目（湘教通[2008]244号）

摘　　要：目的探讨2型糖尿病患者外周血单个核细胞（PBMC）肿瘤坏死因子α（TNF—α）及环氧合酶2（COX-2）mRNA表达情况及基因启动子区域组蛋白H3乙酰化状态。方法分离12例2型糖尿病患者及12名正常对照PBMC，实时定量-PCR法检测TNF—α及COX-2mRNA表达情况。染色质免疫沉淀技术检测TNF—α及COX-2启动子区H3乙酰化状态。结果2型糖尿病患者PBMC TNF-α及COX-2 mRNA表达比正常对照组增高，分别为正常对照的2．28±0．09倍及2．78±0．26倍（P〈0．05）；TNF-α启动子区H3高乙酰化（1．54±0．43比0．97±0．39，P=0．0094）；COX-2启动子区H3高乙酰化（1．20±0．58比0．64±0．21，P=0．0161）。结论2型糖尿病患者PBMC TNF-α及COX-2启动子区域H3高乙酰化可能导致TNF-α及COX-2基因过表达，从而在其发病过程中起重要作用。Objective To investigate the expression of tumor necrosis factor-alpha （TNF-α） and eyclooxygenase-2（COX-2） mRNA and evaluate the status of histone H3 aeetylation at TNF-α and COX-2 promoter in peripheral blood mononuclear cells （PBMCs） from type 2 diabetics. Methods The PBMCs from 12 type 2 diabetics and 12 healthy controls were isolated by Ficoll-Hypaque density gradient eentrifugation. The differential expression of TNF-α and COX-2 mRNA was measured by real-time PCR （ polymerase chain reaction）. Chromatin immunoprecipitation analysis was used to detect the status of H3 acetylation at TNF-α and COX-2 promoter region. Results TNF-α and COX-2 mRNA were overexpressed in PBMCs from Type 2 diabetics as compared with normal controls （ 2. 28 ±0. 09 fold and 2. 78 ±0. 26 fold ）. （ P 〈 0. 05 ）. Compared with normal controls, H3 acetylation at the TNF-α （ 1. 54 ± 0.43 vs 0. 97 ±0. 39, P = 0. 0094 ） and COX-2 （1.20 ± 0. 58 vs 0. 64 ±0. 21 ,P = 0. 0161 ）gene promoter region was elavetedin PBMCs from Type 2 diabetic patients. Conclusion Increased H3 aeetylation at TNF-α and COX-2 promoter in PBMCs from type 2 diabetics may contribute to the pathogenesis of type 2 diabetes through the elevated expressions of TNF-α and COX-2.

关 键 词：糖尿病 2型 肿瘤坏死因子Α 环氧合酶2 单个核细胞 

分 类 号：R587.1[医药卫生—内分泌]