食管癌术后肺部感染对TGF-β1/Smads 信号通路蛋白及应激水平的影响

Effect of postoperative lung infection on TGF-β1/Smads signaling pathway proteins and stress level in patients with esophageal cancer

目的 探究食管癌患者术后肺部感染对转化生长因子β1(TGF-β1)/Smads信号通路蛋白及应激水平的影响。方法 收集2015年3月-2020年3月河南科技大学第一附属医院收治的行食管癌切除术的患者作为本次试验的研究对象,将出现肺部感染的100例患者设为感染组,另选同期术后未出现感染的412例患者作为非感染组,以及同期体检的50名健康者作为对照组。对感染组患者的痰液标本进行病原菌鉴定,酶联免疫吸附实验检测各组患者血清炎症因子白细胞介素-6(IL-6)、IL-8、IL-1β和TGF-β1含量,免疫印迹法检测各组患者肺组织中TGF-β1、Smad2、Smad3、Smad7的蛋白表达,放射免疫分析法检测皮质醇(COR)、促肾上腺皮质激素(ACTH)、丙二醛(MDA)等应激指标,分析肺部感染对TGF-β1/Smads信号通路蛋白及应激水平的影响。结果 共培养分离病原菌269株,其中革兰阴性菌185株占68.77%,革兰阳性菌73株占27.14%,真菌11株占4.09%;感染组和非感染组患者血清炎症因子IL-6、IL-8、IL-1β和TGF-β1高于对照组(P<0.05),且感染组各项因子水平均高于非感染组(P<0.05);与非感染组相比,感染组患者肺组织内TGF-β1、Smad2、Smad3的表达上调,Smad7的表达下调(P<0.05);此外,与非感染组相比,感染组患者应激指标COR、ACTH和MDA均升高(P<0.05);TGF-β1、Smad2、Smad3与应激指标COR、ACTH和MDA呈正相关(P<0.05),Smad7与应激指标COR、ACTH和MDA呈负相关(P<0.05)。结论 食管癌术后肺部感染的致病菌主要为革兰阴性菌,感染患者肺组织内TGF-β1/Smads信号通路被激活,刺激炎症因子的释放,引起应激反应。

OBJECTIVE To explore the effect of postoperative lung infection on transforming growth factor-β1(TGF-β1)/Smads signaling pathway proteins and stress level in patients with esophageal cancer. METHODS Patients who underwent esophageal cancer resection in the First Affiliated Hospital of Henan University of Science and Technology between Mar. 2015 and Mar. 2020 were collected as the research subjects of this experiment. Among them, 100 patients with lung infection were set as infected group, and 412 patients who did not develop infection after surgery during the same time period were regarded as non-infected group, and 50 healthy people who had physical examination during the same period were served as control group. The pathogenic bacteria were identified in the sputum samples of patients in infected group, and the levels of serum inflammatory factors such as interleukin-6(IL-6), interleukin-8(IL-8) and interleukin-1β(IL-1β) were detected by enzyme-linked immunosorbent assay. The protein expressions of TGF-β1, Smad2, Smad3 and Smad7 in lung tissues of each group were detected by Western Blot, and levels of stress indicators such as cortisol(COR), adrenocorticotropic hormone(ACTH) and malondialdehyde(MDA) were measured by radioimmunoassay. The effect of lung infection on TGF-β1/Smads signaling pathway proteins and stress level was analyzed. RESULTS Totally 269 strains of pathogenic bacteria were isolated from the sputum samples of 100 patients in infected group, including 185 strains of Gram-negative bacteria(68.77%), 73 strains of Gram-positive bacteria(27.14%) and 11 strains of fungi(4.09%). The levels of serum inflammatory factors of IL-6, IL-8, IL-1β and TGF-β1 in infected group and non-infected group were significantly increased compared with those in control group(P<0.05), and the levels of various factors in infected group were significantly higher than those in non-infected group(P<0.05). The expressions of TGF-β1, Smad2 and Smad3 in lung tissues of infected group were significantly up-regulated while the expression of Smad7 was significantly down-regulated compared to non-infected group(P<0.05). In addition, compared with non-infected group, the levels of stress indicators of COR, ACTH and MDA were significantly increased in infected group(P<0.05). TGF-β1, Smad2 and Smad3 were positively correlated with stress indicators of COR, ACTH and MDA(P<0.05), and Smad7 was negatively correlated with stress indicators of COR, ACTH and MDA(P<0.05). CONCLUSION The pathogenic bacteria of lung infection after esophageal cancer surgery are mainly Gram-negative bacteria. Infection activates the TGF-β1/Smads signaling pathway in the lung tissues, stimulates the releases of inflammatory factors and induces the stress response.