Cao Qiang, Zhang Shu, Dong Chen, Song Weimin
Department of Environment Health, School of Public Health, Fudan University, Shanghai 200032, China.
Toxicol Lett. 2007 Jul 10;171(3):126-37. doi: 10.1016/j.toxlet.2007.05.007. Epub 2007 May 21.
In order to explore the potential mechanism that animals with cardiopulmonary diseases were more susceptible than healthy animals, the spontaneously hypertensive rats (SHR) as a model of human cardiovascular disease were used. SHR and wistar kyoto rats (WKY) were exposed by intratracheal instillation to fine particles with the doses of 0.0 (saline), 1.6, 8.0 and 40.0mg/kg body weight, respectively. The exposure was done once a day, for three continuous days. The rats were killed after 24h following the last exposure, followed by analysis of bronchoalveolar lavage fluid (BALF) to estimate the lung injury. Meantime, parameters of oxidative stress, cytokines and cell surface receptors related to inflammation and anti-inflammation were also measured. The results showed that lactate dehydrogenase (LDH) activity, percentages of neutrophils and lymphocytes, and expression of TBA-reactive substances and cytokines (IL-1beta, TNF-alpha, MIP-2, OPN, NF-kappaB, CC16 and HO-1) and cell surface receptors (CD44 and TLR-4) were increased in rats, but percentage of macrophages decreased. Meanwhile, at the same dose exposed, the levels of those parameters were higher in SHR than that in WKY rats. The results indicated that inflammation might be one of the mechanisms of lung injury induced by fine particles. Results of comparisons of different response to fine particles between SHR and WKY rats suggested that lung injury induced by fine particles was greater in SHR than that in WKY rats.
为了探究心肺疾病动物比健康动物更易感染的潜在机制，使用自发性高血压大鼠（SHR）作为人类心血管疾病的模型。将SHR和Wistar Kyoto大鼠（WKY）通过气管内滴注分别暴露于剂量为0.0（生理盐水）、1.6、8.0和40.0mg/kg体重的细颗粒物中。每天暴露一次，连续暴露三天。在最后一次暴露后24小时处死大鼠，随后分析支气管肺泡灌洗液（BALF）以评估肺损伤。同时，还测量了与炎症和抗炎相关的氧化应激、细胞因子和细胞表面受体的参数。结果显示，大鼠的乳酸脱氢酶（LDH）活性、中性粒细胞和淋巴细胞百分比、TBA反应性物质和细胞因子（IL-1β、TNF-α、MIP-2、OPN、NF-κB、CC16和HO-1）以及细胞表面受体（CD44和TLR-4）的表达均增加，但巨噬细胞百分比降低。同时，在相同剂量暴露下，SHR中这些参数的水平高于WKY大鼠。结果表明，炎症可能是细颗粒物诱导肺损伤的机制之一。SHR和WKY大鼠对细颗粒物不同反应的比较结果表明，细颗粒物诱导的SHR肺损伤比WKY大鼠更严重。
