摘要
目的 探讨糖尿病心肌病患者外周血单核细胞 Toll 样受体4（TLR4）、肿瘤坏死因子-α（TNF-α）的表达及其与心肌灌注的相关性,初步探讨 TLR4、TNF-α在糖尿病心肌病心肌灌注中的作用,为临床诊治糖尿病心肌病提供新的思路.方法 2型糖尿病（T2-DM）组37例（其中糖尿病心肌病组17例、单纯T2-DM组20例）健康对照组20例.采用SYBR GreenⅠ实时荧光定量RT-PCR检测外周血单核细胞（PBMC）TLR4及TNF-α的mRNA表达.流式细胞仪及ELISA法分别检测单核细胞分泌TLR4、TNF-α蛋白水平.进行心肌灌注单电子发射计算机体层扫描（SPECT）图像可视化分析.结果 糖尿病心肌病组单核细胞TLR4和TNF-α的 mRNA及蛋白表达均显著高于单纯T2-DM组,单纯T2-DM组高于对照组（P均〈0.05）.糖尿病心肌病组心肌灌注总负荷评分（SSS评分） 和总静息评分（SRS评分）显著高于单纯T2-DM组,单纯T2-DM组高于对照组（P均〈0.01）.外周血单核细胞TLR4和TNF-α表达与SSS评分水平呈正相关（r=0.75,P〈0.05;r=0.931,P〈0.005）,与SRS评分水平也呈正相关（r=0.78,P〈0.05;r=0.89,P〈0.005）.DCM组SSS评分、SRS评分与可溶性血管细胞黏附分子呈正相关（r=0.728,P〈0.005;r=0.738,P〈0.005）,与B型利钠肽、左心室射血分数、二尖瓣口舒张早期峰值速度/舒张晚期峰值速度、糖化血红蛋白、空腹血糖、空腹胰岛素、低密度脂蛋白胆固醇无相关性（P均〉0.05）.结论 研究提示TLR4、TNF-α可能在糖尿病心肌病心肌灌注中具有炎症损伤的作用,其机制可能是通过上调 TLR4、TNF-α表达介导级联反应,从而促进内皮分泌可溶性血管细胞黏附分子-1引起心肌灌注的炎症损伤.
Objective To explore the expression of Toll-like receptor 4（TLR4） and tumor necrosis factor-α （TNF-α） on peripheral-blood mononuclear cells（PBMCs） and their correlation with myocardial perfusion in patients with diabetic cardiomyopathy （DCM）.Methods The expression of TLR4 and TNF-α mRNA on PBMCs were examined by SYBR GreenⅠreal-time quantitative reverse transcription ploymerse chain reaction （RT-PCR）, the levels of TLR4 and TNF-α were examined by flow cytometric analysis and enzyme-linked immuno sorbent assay （ELISA） on DCM group （n=20） , Type 2 diabetic group （n=22） and control group （n=20）. Myocardial perfusion was visualized by single-photon emission computed tomography （SPECT）. Results The expressions of TLR4 and TNF-α mRNA/protein on PBMCs in DCM group were significantly higher than in Type 2 diabetic group, and higher in Type 2 diabetic group than in control groups（P〈0.05）; summed stress score （SSS）and summed rest score （SRS） of myocardial perfusion in DCM group were significantly higher than in Type 2 diabetic group, and higher in Type 2 diabetic group than in control groups（P〈0.01）.The expression of TLR4, TNF-α was positively correlated with SSS （r=0.75,P〈0.05;r=0.931,P〈0.005） and SRS（r=0.78,P〈0.005; r=0.789,P〈0.005）. SSS and SRS in DCM group were also positively correlated with soluble vascular cell adhesion molecule-1 （sVCAM-1） （r=0.728,P〈0.005; r=0.738,P〈0.005） but there was no correlation between SSS and SRS and brain natriuretic peptide, LVEF, E/A, HbA1c, FBG, FIN and LDL-C （P〉0.05）.Conclusion The increased expression of TLR4 and TNF-α mRNA/protein on PBMCs and increased serum sVCAM-1 is linked with reduced myocardial perfusion in DCM group. TLR4 and TNF-α may thus play a critical role in the myocardial perfusion inflammation injury in these patients.
出处
《中华心血管病杂志》
CAS
CSCD
北大核心
2011年第6期503-507,共5页
Chinese Journal of Cardiology
关键词
糖尿病
心肌疾病
TOLL
样受体4
肿瘤坏死因子α
心肌灌注
Diabetes mellitus
Cardiomyopathies
Toll-like receptor 4
Tumor necrosis factor-alpha
Myocardial perfusion
