硫酸铅对大鼠心肌Th1/Th2细胞相关细胞因子的影响
Effects of Lead Sulfate on Rat Myocardial Th1- and Th2-Related Cytokines
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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、337.5 μg/kg,1次/d,连续3 d。最后一次染毒24 h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。 Abstract: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 Th1- and Th2- related cytokines in cardiac homogenate supernatant of rats were determined using enzyme-linked immunosorbent assay (ELISA). Furthermore, the protein expressions of Th1- 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)-γ 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 Th1 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-γ 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 Th1 and Th2-related cytokine levels might be a mechanism of cardiac injury induced by lead.
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