宫颈癌合并阴道炎病原菌及其对Nrf2信号通路的影响

Pathogens isolated from cervical cancer patients complicated with vaginitis and influence on Nrf2 signaling pathway

目的 分析宫颈癌合并阴道炎病原菌及其对核因子E2相关因子2(Nrf2)信号通路的影响。方法 选取2021年1月-2022年3月遵义医科大学第三附属医院收治的新发宫颈癌合并阴道炎患者92例为合并组,同期选取单纯新发宫颈癌患者46例为单纯宫颈癌组。收集患者临床资料,采用全自动微生物鉴定仪进行细菌分离和鉴定,采用酶联免疫吸附法检测血清白细胞介素(IL)-6、IL-10、IL-17、转化生长因子-β(TGF-β),实时荧光定量检测人乳头瘤病毒(HPV)主要亚型,蛋白免疫印迹检测癌组织Nrf2、胞浆蛋白kelch样环氧氯丙烷相关蛋白1(Keap1)和低氧诱导因子-1α(HIF-1α)蛋白表达。结果 合并组患者阴道炎既往史、糖尿病比例高于单纯宫颈癌组(P<0.05),合并组患者共分离病原菌54株,以真菌为主为26株。合并组患者检出HPV阳性87例、混合感染11例,单纯宫颈癌组患者检出HPV阳性27例、混合感染2例;合并组患者检出HPV16、HPV18型比例高于单纯宫颈癌组(P<0.05)。合并组患者血清IL-6、IL-10、IL-17和TGF-β水平高于单纯宫颈癌组(P<0.05);合并组患者癌组织Keap1、Nrf2和HIF-1α表达水平高于单纯宫颈癌组(P<0.05)。结论 宫颈癌合并阴道炎患者以真菌感染为主,可能通过调节Nrf2信号通路,加重炎症反应,进而影响HPV感染和宫颈癌发展进程。

OBJECTIVE To observe the pathogens isolated from the cervical cancer patients complicated with vaginitis and the influence on nuclear factor E2-related factor 2(Nrf2) signaling pathway. METHODS Totally 92 cervical cancer patients complicated with vaginitis who were treated in the Third Affiliated Hospital of Zunyi Medical University from Jan 2021 to Mar 2022 were assigned as the combination group, meanwhile, 46 patients with simple cervical cancer were chosen as the simple cervical cancer group. The clinical data were collected from the patients. The pathogens were isolated and identified by automatic microorganism identification system, the serum interleukin(IL)-6, IL-10, IL-17 and transforming growth factor-β(TGF-β) were detected by means of enzyme-linked immunosorbent assay, the major subtypes of human papillomavirus(HPV) were detected by real-time fluorescent quantitative assay, and the expression levels of Nrf2, plasmosin kelch-like epichlorohydrin-associated protein 1(Keap1) and hypoxia-inducible factor-1α(HIF-1α) in cancer tissues were detected by means of Western blot. RESULTS The proportions of patients with previous history of vaginitis, diabetes mellitus were significantly higher in the combination group than in the simple cervical cancer group(P<0.05). Totally 54 strains of pathogens were isolated from the patients of the combination group, 26 of which were fungi. Among the patients of the combination group, 87 were tested positive for HPV, and 11 had mixed infections. Among the patients of the simple cervical cancer group, 27 were tested positive for HPV, and 2 had mixed infections. The proportions of patients who were detected with HPV16 and HPV18 in the combination group were significantly higher than those in the simple cervical cancer group(P<0.05). The levels of serum IL-6, IL-10, IL-17 and TGF-β of the combination group were significantly higher than those of the simple cervical cancer group(P<0.05);the expression levels of cancer tissue Keap1, Nrf2 and HIF-1α of the combination group were significantly higher than those of the simple cervical cancer group(P<0.05). CONCLUSION The patients with fungal infection are dominant among the cervical cancer patients complicated with vaginitis. It may aggravate the inflammatory response by regulating the Nrf2 signaling pathway and then affect the HPV infection and process of development of cervical cancer.