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环境细颗粒物导致的心脏损伤中 Th1 和 Th2 细胞失衡。

Imbalance of Th1 and Th2 cells in cardiac injury induced by ambient fine particles.

机构信息

Department of Environment Health, School of Public Health, Fudan University, the Key Laboratory of Public Health Safety, Ministry of Education, Shanghai 200032, China.

出版信息

Toxicol Lett. 2012 Feb 5;208(3):225-31. doi: 10.1016/j.toxlet.2011.11.012. Epub 2011 Nov 23.

Abstract

The study was to explore the potential immunoregulatory mechanisms linking fine particles and cardiac injury. Wistar kyoto (WKY) rats were exposed by intratracheal instillation to fine particles with the doses of 0.0, 1.6, 8.0 and 40.0mg/kg b.w., respectively. The exposure was conducted once a day, for three consecutive days. Twenty-four hours after the last exposure, the rats were sacrificed. Th1- and Th2-related transcription factors and cytokines were assessed in left ventricle of rats. The mRNA expressions of Th1- and Th2-related transcription factors signal transducer and activator of transcriptionl 1 (STAT1), signal transducer and activator of transcriptional 6 (STAT6), GATA-3 and T-bet were assessed in left ventricle of rats using real-time PCR. Meanwhile, the levels of Th1- and Th2-related cytokines IL-4, IL-13 and interferon gamma (IFN-γ) were determined by ELISA kits in cardiac homogenate supernatant of rats. Furthermore, the protein expression of IL-4 and IFN-γ were detected in myocardium by Western blot. The results of cardiac histology demonstrated exacerbated cardiac lesions and histological characterization of inflammation and degeneration in rats after exposure to fine particles. Moreover, fine particles induced significant increase of IL-4 and IL-13 and decrease of IFN-γ in myocardium of rats. The mRNA expression of STAT1, STAT6 and GATA-3 were up-regulated in left ventricle of rats in a dose-dependent manner, whereas T-bet was significantly down-regulated. The variations of these cytokines demonstrated the imbalance of Th1 and Th2 cytokines existed in cardiac injuries induced by fine particle. The imbalance of Th1/Th2 cytokines might be one of the mechanisms of immunotoxicity of cardiovascular system induced by ambient fine particles.

摘要

该研究旨在探索细颗粒物与心脏损伤相关的潜在免疫调节机制。Wistar 京都(WKY)大鼠通过气管内滴注分别暴露于 0.0、1.6、8.0 和 40.0mg/kg bw 的细颗粒物中。暴露每天进行一次,连续进行三天。最后一次暴露 24 小时后,处死大鼠。评估大鼠左心室中的 Th1 和 Th2 相关转录因子和细胞因子。使用实时 PCR 评估大鼠左心室中 Th1 和 Th2 相关转录因子信号转导和转录激活因子 1(STAT1)、信号转导和转录激活因子 6(STAT6)、GATA-3 和 T-bet 的 mRNA 表达。同时,通过 ELISA 试剂盒测定大鼠心脏匀浆上清液中 Th1 和 Th2 相关细胞因子白细胞介素 4(IL-4)、白细胞介素 13(IL-13)和干扰素γ(IFN-γ)的水平。此外,通过 Western blot 检测心肌中 IL-4 和 IFN-γ的蛋白表达。心脏组织学结果表明,暴露于细颗粒物后大鼠心脏病变加剧,炎症和变性的组织学特征明显。此外,细颗粒物诱导大鼠心肌中 IL-4 和 IL-13 显著增加,IFN-γ 显著减少。STAT1、STAT6 和 GATA-3 的 mRNA 表达在左心室呈剂量依赖性上调,而 T-bet 则显著下调。这些细胞因子的变化表明,细颗粒物诱导的心脏损伤中存在 Th1 和 Th2 细胞因子的失衡。Th1/Th2 细胞因子的失衡可能是环境细颗粒物引起心血管系统免疫毒性的机制之一。

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