多聚鸟嘌呤核苷酸对矽尘致大鼠肺纤维化干预作用及机制研究

发布时间：2018-03-23 17:15

本文选题：矽肺　切入点：多聚鸟嘌呤核苷酸　出处：《中国职业医学》2017年01期

【摘要】：目的观察多聚鸟嘌呤核苷酸(Poly G)对染矽尘大鼠肺纤维化的干预作用,并探讨其作用机制。方法无特定病原体级健康成年雄性SD大鼠随机分为对照组、矽肺模型组和4个干预组(即干预1、2、3、4次组),每组5只。除对照组外,其余5组大鼠均以非暴露式气管插管法一次性予质量浓度为50.0 g/L的矽尘混悬液1.0 m L造模,4个干预组大鼠分别于造模后第1~21天内腹腔注射1、2、3、4次剂量为2.5 mg/kg体质量的Poly G。造模后28 d处死大鼠,观察肺部组织病理学改变情况,以Ashcroft评分法评估肺纤维化程度,以蛋白免疫印迹法测定肺组织内胶原样结构巨噬细胞受体(MARCO)、转化生长因子-β1(TGF-β1)、E-钙黏蛋白(E-cad)、波形蛋白(Vimentin)和α-平滑肌肌动蛋白(α-SMA)的蛋白相对表达水平。结果矽肺模型组大鼠肺泡腔内有大量尘细胞聚集,肺间质内出现弥漫性的胶原沉积,说明矽肺造模成功;干预1次组大鼠肺泡结构基本完整,肺纤维化程度较矽肺模型组明显减轻。与对照组比较,矽肺模型组大鼠肺组织Ashcroft评分和MARCO、TGF-β1、Vimentin、α-SMA的蛋白相对表达水平均升高(P0.05),E-cad相对表达水平下降(P0.05);与矽肺模型组比较,干预1次组大鼠肺组织的TGF-β1、Vimentin和α-SMA的蛋白相对表达水平均下降(P0.05),E-cad相对表达水平升高(P0.05)。Poly G干预次数与大鼠肺组织的Ashcroft评分和MARCO、TGF-β1、E-cad、Vimentin、α-SMA的蛋白相对表达水平之间均无剂量-效应关系。结论 Poly G可改善矽尘所致的大鼠肺组织炎症和纤维化,以在造模后第1天进行一次性干预(2.5 mg/kg体质量,腹腔注射)效果较好,其机制可能与低剂量Poly G抑制上皮间质转化的进程从而减少胶原合成有关。
[Abstract]:Objective to observe the effect of Poly G on pulmonary fibrosis in silicotic rats. Methods healthy male SD rats with no specific pathogens were randomly divided into control group. Silicosis model group and 4 intervention groups (5 rats in each group, 5 rats in each group, except the control group), The rest of the five groups were treated with unexposed endotracheal intubation for a single dose of 50.0 g / L silica dust suspension 1.0 mL. The rats in the four intervention groups were injected intraperitoneally with 1 2 渭 g / L 1. 5 mg/kg body mass respectively within 21 days after the establishment of the model, and the other 5 groups were given intraperitoneal injection of 2. 5 mg / L silica dust suspension at a dose of 2. 5 g / L respectively within 21 days after the establishment of the model. The rats were killed 28 days after Poly G. The changes of lung histopathology were observed and the degree of pulmonary fibrosis was evaluated by Ashcroft score. The relative expression levels of collagen like macrophage receptor (MARCOG), transforming growth factor- 尾 1 (TGF- 尾 1) E-cadn (vimentin) and 伪 -SMAs in lung tissue were measured by Western blot. Results the results showed that the expression of 伪 -SMAs in silicosis model group was higher than that in control group. In the alveolar cavity of rats, a large number of dust cells gathered, The diffuse collagen deposition in the interstitial tissue of the lung indicated that the silicosis model was successful, the alveolar structure of the rats in the first intervention group was basically intact, the degree of pulmonary fibrosis was significantly reduced than that in the silicosis model group, and compared with the control group, In silicosis model group, the Ashcroft score of lung tissue and the relative expression level of MARCO-TGF- 尾 1 Vimentin, 伪 -SMA protein were increased. The relative expression levels of TGF- 尾 1 Vimentin and 伪 -SMA in the lung tissue of the first intervention group were decreased. The relative expression level of P0.05TGF- 尾 1 E-cadVimentin, 伪 -SMA protein was not dose-effective between the relative expression level of P0.05TGF- 尾 1 E-cadVimentin, 伪 -SMA protein and the Ashcroft score of lung tissue and the relative expression level of 伪 -SMA protein. Conclusion Poly G can improve pulmonary inflammation and fibrosis induced by silica dust in rats. The effect of one-off intervention on the first day after the model was 2. 5 mg/kg (intraperitoneal injection) might be related to the inhibition of the process of epithelial interstitial transformation by low dose Poly G and the reduction of collagen synthesis.
【作者单位】：华北理工大学公共卫生学院;新乡医学院公共卫生学院;
【基金】：国家自然科学基金(81273017) 河南省科技攻关项目(162102310491)
【分类号】：R135.2;R563

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