摘要
[目的]通过观察硫酸铅对大鼠心肌辅助性T细胞1(Th1)和辅助性T细胞2(Th2)相关细胞因子的影响,探讨铅对心肌损伤的免疫调节机制,以及铅对心血管系统损伤的可能作用机制。[方法]Wistar大鼠气管滴注硫酸铅,染毒剂量(按体重计)分别为13.5、67.5、337.5μg/kg,1次/d,连续3d。最后一次染毒24h后,取大鼠心脏,采用实时荧光定量-聚合酶链式反应测定大鼠心肌组织中Th1和Th2相关转录因子的mRNA水平,使用酶联免疫吸附法测定心肌组织上清液中Th1和Th2相关细胞因子的表达水平,采用免疫组化方法观察Th1和Th2相关细胞因子的蛋白表达水平。[结果]心肌组织上清液中白细胞介素(IL)-4、IL-13和干扰素-γ(IFN-γ)的表达,染毒组与对照组差异有统计学意义;IL-13的表达,高剂量组与低剂量组间差异有统计学意义。Th1和Th2相关转录因子的mRNA表达水平,染毒组与对照组间差异有统计学意义,且高剂量组与低剂量组间差异有统计学意义。左心室中IL-4和IFN-γ的蛋白表达,染毒组与对照组间差异有统计学意义。[结论]进入肺脏的硫酸铅可致心脏出现明显的炎症反应和免疫毒性,Th1和Th2相关细胞因子水平的改变可能是铅导致心肌损伤的机制之一。
[ Objective ] To explore the potential immunoregulatory mechanisms linking lead sulfate with cardiovascular toxicity. [ Methods ] Wistar rats were exposed to lead sulfate via intratracheal instillation with the doses of 13.5, 67.5, and 337.5 μg/kg （body weight）, respectively. The exposure was conducted once a day for 3 continuous days. Twenty-four hours after the last exposure, the rats were sacrificed. The mRNA expressions of helper T cells （Th） 1- and Th2-related transcription factors were assessed in left ventricle of rats using real-time polymerase chain reaction （PCR）. Meanwhile, the levels of Thl- and Th2- related cytokines in cardiac homogenate supernatant of rats were determined using enzyme-linked immunosorbent assay （ELISA）. Furthermore, the protein expressions of Thl- and Th2-related cytokines in myocardium were detected by immunohistochemistry. [ Results ] The results of cardiac histology demonstrated significant differences in the levels of interleukin （IL）-4, IL-13, and interferon （IFN）-y in cardiac homogenate supernatant between the exposed rats and the controls, as well as in the levels of IL-13 between the high- and low-dose groups. The mRNA expressions of Thl and Th2 in left ventricle between the exposed rats and the controls as well as between the high- and low-dose groups were significantly different. The expressions of IL-4 protein of left ventricular were significantly increased in the exposed rats in comparison with the controls, whereas the expressions of IFN-T protein were significantly reduced. [ Conclusion ] These findings indicate that lead sulfate which enters into the lungs could cause inflammation and immunotoxicity in heart. The changes of Thl and Th2-related cytokine levels might be a mechanism of cardiac injury induced by lead.
出处
《环境与职业医学》
CAS
北大核心
2013年第1期21-25,共5页
Journal of Environmental and Occupational Medicine
基金
国家自然科学基金资助项目(编号:81001229
81172617)
上海市自然科学基金资助项目(编号:09ZR1402400)
