不同中医证型晚期肺腺癌患者血清、诱导痰中炎症因子与 HPA 轴功能的相关性研究

Study on the Correlation between the Inflammatory Factors in the Serum and the Induced Sputum and the Hypothalamic-Pituitary-Adrenal Axis Function in Advanced Lung Adenocarcinoma of Different Syndromes

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DOI：

中文关键词: 肺腺癌炎症因子下丘脑-垂体-肾上腺轴中医证型相关性

英文关键词:lung adenocarcinoma inflammatory factor hypothalamic-pituitary-adrenal axis Chinese medicine syndrome type correlation

基金项目:国家重点基础研究发展计划(973计划)资助项目(No.2009CB523000);2009年度上海市优秀学科带头人计划(A类)项目(No.09XD1400700);上海市卫生局中医药科研基金项目(No.2008L018A)

作者	单位
杜懿杰	复旦大学附属华山医院中西医结合肺、炎症和肿瘤研究室复旦大学中西医结合研究所
曹玉雪	复旦大学附属华山医院中西医结合肺、炎症和肿瘤研究室复旦大学中西医结合研究所
段晓虹	复旦大学附属华山医院中西医结合肺、炎症和肿瘤研究室复旦大学中西医结合研究所
厉蓓	复旦大学附属华山医院中西医结合肺、炎症和肿瘤研究室复旦大学中西医结合研究所
金华良	复旦大学附属华山医院中西医结合肺、炎症和肿瘤研究室复旦大学中西医结合研究所
吴金峰	复旦大学附属华山医院中西医结合肺、炎症和肿瘤研究室复旦大学中西医结合研究所
刘宝君	复旦大学附属华山医院中西医结合肺、炎症和肿瘤研究室复旦大学中西医结合研究所
张红英	复旦大学附属华山医院中西医结合肺、炎症和肿瘤研究室复旦大学中西医结合研究所
董竞成	复旦大学附属华山医院中西医结合肺、炎症和肿瘤研究室复旦大学中西医结合研究所

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中文摘要:

目的研究不同中医证型肺腺癌患者血清、诱导痰中炎症因子与下丘脑-垂体-肾上腺( hypotha-lamic-pituitary-adrenal,HPA) 轴功能变化的相关性。方法根据中医辨证分型不同将 71 例肺腺癌患者分为肾阳虚组( 28 例) 、肺气虚组( 23 例) 、阴虚火旺组( 20 例) 。另选取 41名健康体检者作为健康组。采用 Bio-Plex 悬液芯片检测血清及诱导痰中肿瘤坏死因子( TNF) -α、转化生长因子( TGF) -β、白介素( IL) -6 和干扰素( INF) -γ水平,用放免法检测 24 h 尿游离皮质醇、尿 17-羟皮质类固醇( 尿 17-羟) 、尿 17-酮类固醇( 尿 17-酮) 及血清和唾液皮质醇。结果肾阳虚组血清 IL-6 明显高于其他3 组( P <0. 05) ,24 h 尿游离皮质醇、17-羟皮质类固醇明显低于其他 3 组( P <0. 05) ,尿 17-酮类固醇明显低于健康组及阴虚火旺组( P <0. 05) 。与健康组及肺气虚组比较,肾阳虚组、阴虚火旺组血清 TNF-α明显升高,INF-γ明显降低( P <0. 05) ,肾阳虚组诱导痰 TNF-α、TGF-β明显升高( P <0. 05) ,阴虚火旺组诱导痰 IFN-γ明显降低( P <0. 05) 。肾阳虚组上午8: 00及次日上午 8: 00 血、唾液皮质醇明显降低( P < 0. 05) 。3 组患者血清 TNF-α、血清 IL-6 均与血皮质醇呈较为明显的负相关( r = -0. 26,P =0. 03; r = -0. 25,P =0. 03) ,诱导痰 IL-6 还与唾液皮质醇呈较为明显的负相关( r = -0. 29,P =0. 02) 。血清 IFN-γ与尿 17-羟呈较为明显的正相关( r =0. 21,P =0. 03) 。结论肾阳虚型肺腺癌患者炎症因子上调,HPA 轴功能下降或紊乱最为明显,肺腺癌患者 IL-6、TNF-α和 IFN-γ与HPA 轴功能关系密切。肺腺癌中医证候存在由气虚、阴虚向肾阳虚衰的转化。血清及诱导痰中 IL-6、TNF-α和 IFN-γ及 HPA 轴功能是肺腺癌微观辨证的重要指标。

英文摘要:

Objective To study the correlation between the inflammatory factors in the serum and the induced sputum and the hypothalamic-pituitary-adrenal(HPA) axis function in advanced lung adenocarcinoma patients of different syndromes.Methods Totally 71 patients with advanced lung adenocarcinoma were assigned to three groups according to syndrome differentiation,i.e.,Shen-yang deficiency(SYD) group(28 cases),Fei-qi deficiency(FQD) group(23 cases),and yin deficiency fire excess(YDFE) group(20 cases).Another 41 healthy subjects were enrolled as the normal control group.Sputum was induced and blood samples were collected for measurement of cytokines including tumor necrosis factor α(TNF-α),transforming growth factor β(TGF-β),interleukin-6(IL-6),and interferon γ(INF-γ).The cytokine assay was performed using Bio-Plex Pro multi assay technology.24-h collection of urine was performed and salivary samples of the diurnal rhythm profiles [including urinary free cortisol(UFC),urinary 17-hydroxycorticosteroids(17-OH),urinary 17-ketosteroid(17-KS),and cortisol in the serum and saliva] were obtained for assessment of the HPA axis activity.Results A higher level of serum IL-6 and a lower level of 24-h UFC and 17-OH were found in the SYD group(P<0.05).The urinary 17-KS was obviously lower in the SYD group than in the normal control group and the YDEE group(P<0.05).Compared with the FQD group and the normal control group,a higher serum level of TNF-α and a lower level of IFN-γ were found in the SYD group and the YDFE group(P<0.05).The TNF-α and TGF-β levels in the induced sputum obviously increased in the SYD group(P<0.05).The IFN-γ level in the induced sputum obviously decreased in the YDFE group(P<0.05).The serum and salivary cortisol obviously decreased from 8:00 am to 8:00 am the next morning in the SYD group(P<0.05).The serum cortisol level was negatively correlated with serum TNF-α(r=-0.26,P=0.03) and serum IL-6(r=-0.25,P=0.03).The salivary cortisol level was negatively correlated with IL-6 in the induced sputum(r=-0.29,P=0.02).The serum IFN-γ was positively correlated with urinary 17-OH(r=0.21,P=0.03).Conclusions The inflammatory factors of advanced lung adenocarcinoma patients of SYD syndrome were up-regulated,with the most obvious decreased or disarranged HPA axis functions.The levels of IL-6,TNF-α,and IFN-γ were closely correlated with the HPA axis functions.The transformation from qi deficiency,yin deficiency to Shen-yang deficiency existed in lung adenocarcinoma patients.The levels of IL-6,TNF-α,and IFN-γ in the serum and the induced sputum,as well as the HPA axis functions are important indices for microscopic syndrome typing of lung adenocarcinoma.

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