摘要
目的研究干扰素联合红外线局部照射治疗人乳头瘤病毒(HPV)及相关阴道炎和宫颈炎的作用及相关机制。方法将30只雌性SD大鼠采用随机数字表法分为对照组、模型组和治疗组,每组各10只。模型组和治疗组大鼠建立HPV16感染所致阴道炎和宫颈炎模型,治疗组大鼠给予干扰素α-2b(IFNα-2b)联合红外光局部照射治疗,对照组和模型组不予任何治疗。观察3组大鼠阴道分泌物,并对炎症细胞的数量和形态进行分析,实时荧光定量聚合酶链式反应(qRT-PCR)法测定血清中HPV16-DNA拷贝数,酶联免疫吸附试验(ELISA)检测血清中干扰素-γ(IFN-γ)和白细胞介素-10(IL-10)的表达水平,蛋白质印迹(Western blotting)检测阴道和宫颈组织中叉头/翼状螺旋转录因子3(Foxp3)、T细胞表达的T盒家族(T-bet)和GATA连接蛋白3(GATA-3)蛋白的表达。结果与模型组相比,治疗组大鼠阴道分泌物菌落数明显减少,阴道和宫颈组织炎症细胞浸润减少。与对照组相比,模型组大鼠阴道和宫颈组织中炎症细胞总数、炎症细胞总面积、炎症细胞总周长、炎症细胞等效圆直径、炎症细胞最大直径、炎症细胞最小直径、炎症细胞积分吸光度总和及炎症细胞平均黑度总和等8项指标均显著升高,差异均有统计学意义(P<0.05);与模型组相比,治疗组阴道和宫颈组织中的上述8项指标均显著降低,差异均有统计学意义(P<0.05)。与对照组相比,模型组大鼠血清HPV16-DNA拷贝数、IL-10水平显著升高,IFN-γ水平显著降低,差异有统计学意义(P<0.05);与模型组相比,治疗组大鼠血清HPV16-DNA拷贝数、IL-10水平显著降低,IFN-γ的水平显著升高,差异有统计学意义(P<0.05)。与对照组相比,模型组大鼠阴道和宫颈组织中Foxp3和GATA-3蛋白的相对表达显著降低,而T-bet蛋白的相对表达显著升高,差异均有统计学意义(P<0.05);与模型组相比,治疗组大鼠Foxp3和GATA-3蛋白的相对表达显著升高,而T-bet蛋白的相对表达显著降低,差异均有统计学意义(P<0.05)。结论IFNα-2b联合红外光对HPV感染所致阴道炎和宫颈炎大鼠疗效显著,其机制可能与调节转录因子Foxp3、GATA-3和T-bet的功能、维持Th1/Th2细胞因子动态平衡、调节免疫紊乱有关。
Objective To study the effect and mechanism of interferon combined with infrared local radiation in the treatment of human papillomavirus(HPV)related vaginitis and cervicitis.Methods A total of 30 female SD rats were divided into control group,model group and treatment group by random number table method,with 10 rats in each group.The model group and treatment group were established HPV vaginitis and cervicitis model infected by HPV16,the treatment group was treated with interferonα-2b(IFNα-2b)combined with infrared local radiation.The vaginal secretion was observed,and the numbers and morphologies of inflammatory cells in vagina and cervix were analysed,the HPV16-DNA copies were detected by real-time polymerase chain reaction(qRT-PCR),the serum interferon-γ(IFN-γ)and Interleukin-10(IL-10)were detected by enzyme-linked immunosorbent assay(ELISA),the expression of forkhead/winged helix transcription factor 3(Foxp3),T box expressed in T cells(T-bet)and GATA binding factor-3(GATA-3)proteins in vagina and cervix tissues were detected by Western blotting.Results Compared with the model group,the number of colonies in vaginal secretions of rats in the treatment group was significantly reduced,and the infiltration of inflammatory cells in the vagina and cervix tissues was reduced.Compared with the control group,the total number of inflammatory cells,total area of inflammatory cells,total circumference of inflammatory cells,equivalent circle diameter of inflammatory cells,maximum diameter of inflammatory cells,and inflammatory cells in the vagina and cervical tissues,the minimum diameter,the sum of the integral optical density of inflammatory cells,and the sum of the average blackness of inflammatory cells of the model group were all significantly increased,and the differences were statistically significant(P<0.05);compared with the model group,the above-mentioned 8 indicators in the vaginal and cervical tissues of the treatment group all were significantly reduced,and the differences were all statistically significant(P<0.05).Compared with the control group,the serum HPV16-DNA copy number and IL-10 levels of the model group increased significantly,and the level of IFN-γdecreased significantly,the differences were statistically significant(P<0.05);compared with the model group,serum HPV16-DNA copy number and the level of IL-10 in the treatment group decreased significantly,and the expression level of serum IFN-γincreased significantly,and the differences were statistically significant(P<0.05).Compared with the control group,the relative expression of Foxp3 and GATA-3 protein in the vagina and cervix tissues of the model group was significantly reduced,while the relative expression of T-bet protein was significantly increased,and the differences were statistically significant(P<0.05);Compared with the model group,the relative expression of Foxp3 and GATA-3 protein in the treatment group was significantly increased,while the relative expression of T-bet protein was significantly reduced,and the differences were statistically significant(P<0.05).Conclusion IFNα-2b combined with infrared local radiation had significant efficacy in the treatment of vaginitis and cervicitis rats infected by HPV,the potential mechanisms might relative with regulation of transcription factor Foxp3,GATA-3 and T-bet,maintain the dynamic balance of Th1/Th2 cytokines and regulation of immune disorders.
作者
刘翠萍
张颖
李宁莉
LIU Cui-ping;ZHANG Ying;LI Ning-li(Department of Orthopedics,Xijing Hospital 986 Hospital,Xi'an Shaanxi 710054,China;Department of Obstetrics and Pediatrics,Xijing Hospital 986 Hospital,Xi'an Shaanxi 710054,China;Department of Oncology and Hematology,Xijing Hospital 986 Hospital,Xi'an Shaanxi 710054,China)
出处
《临床和实验医学杂志》
2021年第13期1353-1357,共5页
Journal of Clinical and Experimental Medicine
基金
国家自然科学基金青年项目(编号:81302243)。
