环境细颗粒物亚慢性染毒对大鼠炎症损伤及免疫功能的影响研究  

Study of ambient PM_(2.5) on the influence of the inflammation injury and the immune function of subchronic exposure rats

作　　者：徐东群[1] 黄宁华[2] 王秦[1] 刘红刚[3] 岳常丽[3] 

机构地区：[1]中国疾病预防控制中心环境与健康相关产品安全所,北京100021 [2]北京大学医学部公共卫生学院 [3]首都医科大学附属北京同仁医院

出　　处：《卫生研究》2008年第4期423-428,共6页Journal of Hygiene Research

基　　金：国家自然科学基金资助项目(No20077033)

摘　　要：目的建立细颗粒物的亚慢性暴露动物模型,探讨PM2.5对大鼠炎症损伤及免疫功能的影响。方法应用气管滴注建立细颗粒物的亚慢性暴露动物模型;光镜下观察各脏器病理学变化;采用相应的试剂盒测定肺泡灌洗液中的总蛋白和唾液酸水平;ELISA方法检测细胞因子IL-6和TNF-α水平,采用RT-PCR方法检测肺组织中这两种细胞因子的表达水平;收集肺泡巨噬细胞,采用孔雀绿比色法检测巨噬细胞的吞噬功能;取脾脏,采用MTT方法检测淋巴细胞的增殖功能。结果在染毒后的大鼠肺内均观察到异物性肉芽肿形成;在肝脏血窦内观察到有单核吞噬细胞聚集形成肉芽肿的趋势;在肺门淋巴结和肝脏、肾脏血管内观察到明显的吞噬PM2.5的巨噬细胞和游离的PM2.5。总蛋白和唾液酸水平随着暴露时间和剂量升高而增加。在观察的前3个月,染毒组TNF-α表达水平逐渐升高,而在6个月时,TNF-α水平明显降低;IL-6表达水平随着染毒剂量的增加而升高,并呈现明显的剂量-效应关系,染毒3个月后最高,而在6个月后表达水平回落。肺泡巨噬细胞的吞噬功能随着剂量的增加而下降。淋巴细胞增殖功能没有出现显著性变化。结论细颗粒物的亚慢性暴露可以引起机体的持续炎症损伤;细颗粒物对免疫系统的损伤随着剂量和暴露时间的增加而增加,细颗粒物引起的细胞因子网络紊乱会加重免疫系统的损伤;细颗粒物引起巨噬细胞吞噬功能下降,是肺部慢性疾病的致病机制之一。Objective To explore ambient PM2.5 the influence of the inflammation injury and the on immune function. Methods The model rats were administered with PM2.5 by the intratracheal instillation. The pathological varieties of rat＇s lungs and other important organs were observed by light microscope. The protein and SA levels in bronchoalveolar lavage fluids（BALF） were detected by relevant kits. The TNF-α,and IL-6 levels in the BALF were detected by ELISA, and the mRNA expression levels in the lung tissue were observed by RT-PCR. The AM were collected to detect the phogacytic function. The ConA-stimulated T lymphocyte proliferation tests were performed to research the proliferation of spleen. Results Foreign-body granulomas were observed in the lungs of exposed rats. Monocytes-macrohages assembling in blood sinus of liver and the trend to form the granulomas were observed. Alveolar macrophages containing PM2.5 and dissociative PM2.5 were obviously observed in lung visceral pleural lymphatics and the blood vessels in lung and kidney. The number of the granulomas in the lungs of the rats become more and more as times goes on. The concentrations of total protein and SA in BALF were increased with the dose and time of exposure. TNF-u levels in the BALF increased by the dose and exposure time during 3 months, but TNF-α levels in the BALF decreased significantly on the 6th month. The expression levels of IL- 6 in the BALF increased by the dose. It showed the dose-response relationship. The highest expression level of IL-6 was detected on the 3rd month. The expression level of IL-6 decreased on the 6th month. Phagocytiosis functions of AM were impaired by PM2.5, which may in turn impair the nonspecific defenses function of airway. But the splenic lymphocyte proliferation were not obviously changed. Conclusion The persistent inflammatory injury was induced by the subchromic exposure to PM2.5 . The injury of immunological system were increased with the dose and the time of the exposure. The cytokine net was disordered by

关 键 词：环境细颗粒物 大鼠 亚慢性染毒 炎症损伤 免疫功能 环境毒理 

分 类 号：R56[医药卫生—呼吸系统] X513.031[医药卫生—内科学]