Department of Cardiology, the First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei Province, China.
Arch Med Res. 2010 Aug;41(6):423-9. doi: 10.1016/j.arcmed.2010.08.008.
TLR4 has been shown to mediate inflammation in animal models of myocardial ischemia/reperfusion injury (MI/RI). Here we hypothesized that TLR4 on peripheral blood mononuclear cells (PBMCs) may be involved in the inflammatory response in this type of clinical event.
Seventy two patients with acute myocardial infarction (AMI) who underwent thrombolysis were assigned into reperfusion group (n = 43) and non-reperfusion group (n = 29) according to recanalization of infarct-related artery (IRA) and 40 healthy volunteers were enrolled in this experiment. Eight mL of venous blood was taken from all patients 0 h before and 2, 6, 12, and 24 h after thrombolysis. Flow cytometry (FCM) was used to detect TLR4 protein expression and real-time quantitative RT-PCR was performed to determine TLR4 mRNA and myeloid differentiation protein-88 (Myd88) mRNA expression. The concentration of tumor necrosis factor-α (TNF-α) in plasma was evaluated using enzyme-linked immunosorbent assay (ELISA).
Compared with controls, all detected indicators in AMI patients were upregulated before thrombolysis (p <0.01). After thrombolysis, they were further increased. In reperfusion group, all attained their peaks in earlier hours and the peak values were lower compared with non-reperfusion group. In both cases, either reperfusion or non-perfusion, TLR4 mRNA expression was positively correlated with the levels of Myd88 mRNA (r = 0.886 and 0.694, p <0.01), respectively.
TLR4 expression on PBMCs was markedly elevated in AMI patients either reperfused or non-reperfused. Inflammatory reaction by activated TLR4 in MI/RI in patients may be through TLR4-Myd88-dependent signal pathway.
TLR4 已被证明在动物模型的心肌缺血/再灌注损伤（MI/RI）中起介导炎症作用。在这里，我们假设外周血单核细胞（PBMCs）上的 TLR4 可能参与这种临床事件的炎症反应。
根据梗死相关动脉（IRA）再通情况，将 72 例接受溶栓治疗的急性心肌梗死（AMI）患者分为再灌注组（n = 43）和非再灌注组（n = 29），并纳入 40 例健康志愿者进行本实验。所有患者在溶栓前 0 小时、溶栓后 2、6、12 和 24 小时抽取 8ml 静脉血。采用流式细胞术（FCM）检测 TLR4 蛋白表达，实时定量 RT-PCR 检测 TLR4 mRNA 和髓样分化蛋白-88（Myd88）mRNA 表达。采用酶联免疫吸附试验（ELISA）检测血浆肿瘤坏死因子-α（TNF-α）浓度。
与对照组相比，AMI 患者溶栓前所有检测指标均升高（p <0.01）。溶栓后进一步升高。在再灌注组，所有指标在更早的时间达到峰值，且峰值低于非再灌注组。在再灌注或非再灌注的情况下，TLR4 mRNA 表达与 Myd88 mRNA 水平呈正相关（r = 0.886 和 0.694，p <0.01）。
再灌注或非再灌注的 AMI 患者 PBMCs 上 TLR4 表达明显升高。激活的 TLR4 在 MI/RI 中的炎症反应可能通过 TLR4-Myd88 依赖的信号通路。
