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目的研究内质网应激性凋亡途径在粉尘致大鼠肺纤维化过程中的作用。方法 36只健康成年雄性Wistar大鼠随机分为对照组及染尘组。采用非暴露式气管内注入法染尘,染尘组一次性注入含质量浓度为50 g/L粒径<5μm石英粉尘的生理氯化钠溶液1 ml,对照组注入等体积无菌生理氯化钠溶液,每组分别于染尘结束后14、28、56 d随机处死6只大鼠,进行支气管肺泡灌洗,计算肺系数,羟脯氨酸法检测总胶原蛋白的水平,苏木精-伊红染色法观察肺组织的病理变化;流式细胞术检测肺泡巨噬细胞凋亡率;Western-blot法检测肺泡巨噬细胞Caspase-12的蛋白表达水平。结果与对照组比较,染尘组大鼠在染尘后第14天细胞凋亡率和Caspase-12的蛋白表达水平均升高(P<0.05);染毒后第28天肺系数及肺组织总胶原蛋白水平也升高(P<0.05),细胞凋亡率和Caspase-12的蛋白表达水平持续升高(P<0.05);染毒后第56天,以上指标仍进一步升高(P<0.05)。结论内质网应激性凋亡途径可能参与了粉尘致大鼠肺纤维化的发病机制。
Objective To study the role of endoplasmic reticulum (ER) -dependent apoptosis pathway in pulmonary fibrosis induced by dust in rats. Methods Thirty - six healthy adult male Wistar rats were randomly divided into control group and dyed group. The non-exposed intratracheal instillation method was used to infect 1 ml of physiological sodium chloride solution containing 50 g / L quartz dust with a particle size of <5μm into the dust-exposed group. The control group was injected with an equal volume of sterile physiological chloride Sodium solution. Six rats were randomly sacrificed at 14, 28 and 56 days after the end of the dust exposure. Bronchoalveolar lavage was performed to calculate the lung coefficient. Hydroxyproline method was used to detect the level of total collagen. Hematoxylin- The pathological changes of lung tissue were observed by eosin staining. The apoptosis rate of alveolar macrophages was detected by flow cytometry. The protein expression of Caspase-12 in alveolar macrophages was detected by Western-blot. Results Compared with the control group, the apoptotic rate and the protein expression of Caspase-12 increased on the 14th day after infection in the dust-exposed group (P <0.05). On the 28th day after exposure, the lung coefficient and lung tissue (P <0.05). The apoptotic rate and protein expression of Caspase-12 increased continuously (P <0.05). On the 56th day after treatment, the above indexes were still increased (P < 0.05). Conclusion The ER stress-induced apoptosis pathway may be involved in the pathogenesis of dust-induced pulmonary fibrosis in rats.