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Toll 样受体 4 参与了百草枯中毒后小鼠的心肌损伤。

Toll-like receptor 4 is involved in myocardial damage following paraquat poisoning in mice.

机构信息

Department of Emergency, The First Affiliated Hospital, China Medical University, Shenyang, 110001, China.

出版信息

Toxicology. 2013 Oct 4;312:115-22. doi: 10.1016/j.tox.2013.08.009. Epub 2013 Aug 19.

DOI:10.1016/j.tox.2013.08.009
PMID:23969119
Abstract

The ingestion of the herbicide paraquat (PQ) can cause multiple organ injury including cardiac lesions. However, the underlying mechanism of myocardial damage is not known. Toll-like receptor 4 (TRL4) is a pattern-recognition receptor in the innate immune response to microbial pathogens. TLR4 is involved in heart dysfunction such as septic shock or myocardial ischemia. We investigated whether TLR4 would be linked to the pathogenesis of heart disease due to PQ exposure. Wild type mice (WT) and TLR4-deficient mice were injected intraperitoneally with 75mg/kg of PQ to induce myocardial damage and tested for echocardiographic assessment, histopathology, pro-inflammatory cytokine and TLR4 expression. WT mice after PQ exposure displayed deteriorate cardiac function, pathological damages, increased TLR4 mRNA and protein levels as well as myocardial TNF-α and IL-1β levels. Compared with WT mice, TLR4-deficient mice were significantly resistant to the PQ-induced injury. We concluded that the TLR4 was required as a mediator and played an important role in myocardial damage due to PQ.

摘要

百草枯(PQ)的摄入会导致多器官损伤,包括心脏损伤。然而,心肌损伤的潜在机制尚不清楚。Toll 样受体 4(TLR4)是先天免疫对微生物病原体反应的一种模式识别受体。TLR4 参与败血症休克或心肌缺血等心脏功能障碍。我们研究了 TLR4 是否与 PQ 暴露引起的心脏病发病机制有关。野生型小鼠(WT)和 TLR4 缺陷型小鼠经腹腔注射 75mg/kg 的 PQ 诱导心肌损伤,并进行超声心动图评估、组织病理学、促炎细胞因子和 TLR4 表达检测。PQ 暴露后的 WT 小鼠心脏功能恶化,病理损伤,TLR4 mRNA 和蛋白水平以及心肌 TNF-α和 IL-1β水平升高。与 WT 小鼠相比,TLR4 缺陷型小鼠对 PQ 诱导的损伤具有明显的抗性。我们得出结论,TLR4 作为一种介质是必需的,并在 PQ 引起的心肌损伤中发挥重要作用。

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