巴豆醛暴露致雄性大鼠肺损伤作用研究

Effect of crotonaldehyde exposure induced lung injury in male rats

目的观察巴豆醛对雄性大鼠的肺损伤作用,探讨其毒作用机制。方法无特定病原体级健康雄性Wistar大鼠随机分为对照组和低、中、高剂量组,每组10只,分别予剂量为0.00、2.11、4.22和8.44 mg/kg体质量的巴豆醛溶液灌胃染毒,每天1次,连续25 d。末次染毒结束后处死大鼠,分离肺脏检测脏器系数并进行组织病理学检查,采用酶联免疫吸附实验测定肺组织中肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β、IL-4、IL-6和干扰素(IFN)-γ的水平。结果中和高剂量组大鼠肺组织均出现肺损伤的早期炎症性病理学改变,主要表现为肺泡结构破损、间隔增宽且有炎性细胞浸润、充血,细支气管上皮增厚、可见红细胞及炎性细胞浸润;高剂量组的改变更严重。大鼠肺脏脏器系数以及肺脏组织中IFN-γ、IL-4、IL-6、IL-1β、TNF-α水平均呈现随巴豆醛染毒剂量的增加而升高的剂量-效应关系(P<0.01)。结论巴豆醛可上调大鼠肺组织中炎性细胞因子水平,导致大鼠肺组织发生炎性损伤。

Objective To observe the effect of crotonaldehyde exposure on lung injury in male rats,and to explore the mechanism of toxic action. Methods Specific pathogen free healthy adult male Wistar rats were randomly divided into 4groups with 10 rats in each group： a control group and low-,medium- and high-dose groups. Rats were treated with 0. 00,2. 11,4. 22,8. 44 mg / kg body weigh crotonaldehyde by intra-gastric administration,once per day for 25 consecutive days.After the last treatment,rats were secrificed and the lung was isolated. Lung organ coefficients were calculated and the pathologic changes in lung tissues were observed. The levels of interferon（ IFN）-γ,interleukin（ IL）-1 β,IL-4,IL-6 and tumor necrosis factor（ TNF）-α in lung tissue were determined by enzyme-linked immunosorbent assay. Results The lung tissue in both the medium- and high-dose group showed early inflammatory pathological changes with alveolar structure damage,interval widened and inflammatory cell infiltration,congestion,bronchiolar epithelial hyperplasia,visible red blood cells and inflammatory cells infiltration. The changes in the high-dose group were more severe than that in the medium-dose group. The lung organ coefficient and the levels of IFN-γ,IL-1 β,IL-4,IL-6,TNF-α in lung tissue were increased in dose-effect relations（ P〈0. 01）. Conclusion Crotonaldehyde can increase the level of inflammatory factors in the lung tissues of rats,causing inflammatory injury of lung tissue.