宣威肺癌患者肺组织中无机物的赋存与NF-κB信号通路激活以及iNOS表达的相关研究

Association of Inorganics Accumulation with the Activation of NF-κB Signaling Pathway and the iNOS Expression of Lung Tissue in Xuanwei Lung Cancer Patients

背景与目的室内空气污染不仅会诱发哮喘,也会导致慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD),甚至促进肺癌发生。随着宣威肺癌的病因学研究,发现室内空气污染最终造成肺部无机颗粒物的沉积,这些物质可以造成肺泡细胞损伤、信号通路激活,最终促进肿瘤的发生。本研究旨在探讨宣威肺癌患者肺部中无机杂质的赋存以及核转录因子(nuclear factorκB,NF-κB)-诱导型一氧化氮合成酶(inducible nitric oxide synthase,i NOS)信号通路的激活情况。方法选取48例2013年12月-2014年11月在昆明医科大学第三附属医院行手术治疗的宣威肺癌患者与其他地区的肺癌患者作为研究对象,用透射电镜(transmission electron microscope,TME)对患者术后标本进行超微结构的观察,探究无机颗粒物的赋存情况;对患者的血清行细胞因子检测;对术后的标本行免疫组化以及蛋白质印迹(Western blot),了解NF-κB-p65蛋白以及i NOS蛋白的表达;对肺癌组织中和尿液中的8-OHd G赋存进行检测。结果在宣威肺癌患者癌旁组织的肺泡II型细胞、巨噬细胞中可见到大量纳米级无机物赋存;对无机物进行元素分析,含有硅(Silicon,Si)成分;宣威地区患者血清中白介素(interleukin,IL)-1β(31.50±19.16)pg/m L较其他地区肺癌患者(11.33±6.94)pg/m L高,差异有统计学意义(P<0.01);宣威肺癌与其他地区肺癌患者的术后病理组织中癌组织有NF-κB-p65和i NOS表达,较非宣威地区明显升高;癌旁和正常组织之间未见明显差异;宣威肺癌组织和尿液8-OHd G较非宣威地区肺癌患者高,肺癌患者尿液中的8-Ohd G(40.124±8.597)ng/mg Cr与其他地区患者(25.673±7.986)ng/mg Cr相比,差异有统计学意义(P<0.05)。结论肺部无机物的赋存以及NF-κB-i NOS信号通路的激活可能促进了宣威肺癌的发生。

Background and objective Indoor air pollution induces asthma, leads to chronic obstructive pulmonary disease, and may promote lung cancer. Our previous studies found that the accumulation of inorganic particulate matter that is due to indoor air pollution can lead to damage to alveolar cells and activation of signaling pathway, and ultimately provoke tumorigenesis. The aim of this study is to explore the accumulation of inorganics and activation of nuclear factor κB（NF-κB）-inducible nitric oxide synthase（i NOS） signaling pathway of lung tissue in Xuanwei lung cancer patients. Methods From December 2013 to November 2014, 48 cases Xuanwei patients with lung cancer who underwent surgical treatment from the Third Affiliated Hospital of Kunming Medical University were enrolled in this study and compared with lung cancer patients from other regions. The ultrastructure of postoperative specimens was observed by transmission electron microscopy（TEM） to explore the occurrence of inorganic particles. Serum cytokines were analyzed. Then, the expression levels of NF-κB-p65 pro-tein and i NOS protein in postoperative specimens was explored by immunohistochemistry and Western blot. Finally, 8-OHd G accumulation in lung cancer tissues and urine was measured. Results A large number of nanoscale inorganics were observed in alveolar type II cells and macrophages located in adjacent tissues of lung cancer with Xuanwei patients. Silicon（Si） content was found in inorganic elemental analysis. The serum interleukin（IL）-1β levels（31.50±19.16） pg/m L of Xuanwei lung-cancer patients were remarkably higher than those from other regions（11.33±6.94） pg/m L（P〈0.01）, with statistically significant difference. The pathological tissues of Xuanwei lung-cancer patients express NF-κB-p65, and i NOS expression were significantly higher than those of patients from non-Xuanwei regions. No significant difference was found between cancerous and normal adjacent tissues. Xuanwei lung-cancer tissues and urine 8-OHd G level（40.124±8.597） ng/mg Cr were significantly higher than those of patients from other regions（25.673±7.986） ng/mg Cr（P〈0.05）, with statistically significant difference. Conclusion The accumulation of inorganics and the activation of NF-κB-i NOS signaling pathway may contribute to Xuanwei lung cancer.