NF-κB炎性通路在稀土氧化钕颗粒物致大鼠肺炎性损伤过程中的作用及机制研究

发布时间：2018-07-13 13:36

【摘要】：目的探讨稀土氧化钕颗粒物(Nd2O3)致大鼠肺炎性损伤过程中,NF-κB炎性通路作用及其机制。方法选用SPF级健康成年雄性SD大鼠70只(体重200±10g),采用气管非暴露插管灌注法进行染尘,建立肺炎性损伤模型。采用稀土氧化钕粉尘悬液100mg/kg,0.8 ml和0.9%生理盐水0.8ml一次性染尘,分别于染尘后第3、7、14、21、28d各处死7只实验组和7只对照组大鼠。肺组织HE染色,同时采用天狼猩红染色,偏光显微镜下观察Ⅰ、Ⅲ型胶原纤维。EMSA法测定大鼠新鲜肺组织中NF-κB的含量。Western blot法测定大鼠新鲜肺组织中p65、p-p65、PIKKβ蛋白的表达。取大鼠支气管肺泡灌洗液(BALF),ELISA法分别测定实验组和对照组大鼠BALF中细胞因子的含量。结果(1)肺HE染色结果显示肺炎性损伤模型造模成功。稀土氧化钕颗粒物致实验大鼠肺组织纤维化过程中可见Ⅰ、Ⅲ型胶原纤维的大量增生,染尘后早期主要以Ⅰ型胶原纤维增生为主。其Ⅰ、Ⅲ型胶原纤维明显增加与对照组比较差异均有统计学意义(P0.05)。(2)EMSA结果显示实验组大鼠NF-κB活性增加;在14天达到最高值后又呈降低的变化趋势,但均高于对照组(P0.05);(3)实验组大鼠肺组织中p-p65、PIKKβ蛋白的表达均出现先增加后减少,在14天达到最高值后又呈下降的变化趋势,但均高于对照组(P0.05)。P65与对照组比较差异无统计学意义(P0.05);(4)实验组大鼠较对照组大鼠BALF中促炎性和抗炎性细胞因子均升高(P0.05),且在实验组中促炎性和抗炎性细胞因子均出现先增加后减少。在14天达到最高值后又呈下降的变化趋势,但均高于对照组(P0.05)。结论稀土氧化钕粉尘进入大鼠肺组织后,启动了NF-κB炎性通路,导致肺组织中促炎性细胞因子和抗炎性细胞因子以及肺组织中蛋白含量均发生了明显的变化,且Ⅰ、Ⅲ型胶原纤维大量增生,最终导致大鼠肺损伤。
[Abstract]:Objective to investigate the role and mechanism of NF- 魏 B inflammatory pathway in neodymium oxide particles (ND _ 2O _ 3) induced pneumonia injury in rats. Methods 70 healthy male Sprague-Dawley rats of SPF grade (body weight 200 卤10 g) were used to establish pneumonic injury model. Neodymium oxide dust suspension (100mg 路kg ~ (-1) and 0.9% normal saline (0.8ml) were used to dye the dust at one time. Seven rats in the experimental group and seven in the control group were killed on the 28th day after exposure to neodymium oxide dust. Lung tissue was stained with HE and Sirius red staining. The content of NF- 魏 B in fresh lung tissue of rats was determined by polarizing microscope. The expression of p65- p-p65- PIKK 尾 in fresh lung tissue was detected by Western blot method. Bronchoalveolar lavage fluid (BALF) was used to detect cytokines in BALF of experimental group and control group. Results (1) Lung HE staining showed that the model of pneumonic injury was successful. During the process of pulmonary fibrosis induced by neodymium oxide particles, a large number of type 鈪，

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