Th17细胞和Th1/Th2/Th17相关细胞因子水平在良性前列腺增生患者中的意义

Levels of Th17 cells and Th1/Th2/Th17-related cytokines in benign prostatic hyperplasia and its significance

目的探讨在良性前列腺增生(BPH)患者中辅助性T细胞(Th)17和Th1/Th2/Th17相关细胞因子的表达及意义。方法收集2013至2014年住院手术且有完整病历资料的80例行尿道前列腺电切术(TURP)的BPH患者的术前外周血及术中前列腺组织标本,根据病理学检查是否合并组织学炎症分为单纯组和炎症组。另选取20例健康男性作为对照组。采用流式微球技术检测血浆Th17细胞相关细胞因子(IL-17、IL-23)、Th1细胞相关细胞因子(IFN-γ、IL-2)和Th2细胞相关细胞因子(IL-4、IL-6)的水平;流式细胞术检测外周血单个核细胞(PBMC)中Th17细胞的比例;免疫组化法检测IL-17蛋白在前列腺组织中的表达。结果 (1)80例TURP切除的前列腺组织标本中,有60例(75%)患者前列腺组织中存在组织学炎症,依据组织学炎症情况分为BPH轻度(n=31)、中度(n=18)和重度炎症组(n=11);另20例不存在组织学炎症(单纯组)。(2)BPH炎症各亚组患者血浆IL-17含量明显高于对照组和单纯组患者(P均<0.05),但轻、中、重度炎症亚组间比较无统计学差异(P均>0.05)。其他细胞因子(IL-23、IFN-γ、IL-6、IL-4、IL-2)含量在不同组别之间比较水平相近(P均>0.05)。(3)流式细胞术检测结果,BPH炎症各亚组PBMC中Th17细胞百分比均较单纯组有升高的倾向,但差异无统计学意义(P均>0.05)。(4)在前列腺组织中,BPH轻、中、重炎症组IL-17蛋白表达水平分别高于对照组和BPH单纯组(P均<0.05),IL-17蛋白表达水平与BPH的组织学炎症程度呈正相关(r=0.501,P=0.014)。结论 Th1和Th2细胞对BPH的影响可能不大;而Th17细胞存在升高趋势,其相关细胞因子IL-17在血浆中的含量和前列腺组织中的表达水平明显增高。推测Th17可能经前列腺组织中的炎症因子作用迁移至前列腺组织中而促进前列腺增生。

Objective To study helper T cells （Th） 17 and Th1/Th2/Th17-related cytokines levels in ber, ign prostatic hyperplasia （ BPH ） and its significance. Methods Eighty BPH patients with complete medical records who were hospitalized and underwent transurethral resection of prostate （TURP） between 2013 and 2014 were selected. Preoperative peripheral blood and intraoperative prostate tissues specimens were collected. The patients were divided into simple group and inflammation group according to whether there was histological inflammation based on pathological cheek results. Twenty healthy men were selected as control group. Cytometric bead array （CBA） technique was used to detect the levels of plasma Th17 cell-related cytokines [ interleukin （IL） -17, IL-23 ], Th1 cell-related cytokines [ interferon-γ （ IFN-γ）, IL-2 ] and Th2-related cytokines（ IL-4, IL-6）. Flow eytometry was used to detect the proportion of Th17 cells in peripheral blood mononuclear cells （PBMC）. Immunohistochemistic method was used to detect the expression of IL-17 protein in prostate tissues. Results （ 1 ） Out of 80 prostate tissue specimens resected by TURP,60 （75%） existed histological inflammation which were divided into mild-（ n = 31 ） , moderate-（ n = 18 ）and severe-（ n = 11 ）inflammation group according to the severity of histological inflammation, and there were no inflammation in the other 20 cases （simple group）. （2） The contents of plasma IL- 17 in all inflammation subgroups were significantly higher than those in control group and simple group （ all P 〈 0.05 ） , but there were no significant differences in mild-, moderate- and severe-inflammation group （ all P 〉 0.05 ）. The contents of plasma other cytokines （ IL-23, IFN-γ, IL-6, IL-4, IL-2） were similar among all groups （ all P 〉 0.05 ）. （ 3 ） Flow cytometry results showed that the proportions of Th17 cells in PBMC in all inflammation subgroups had a elevated tendency compared with simple group, but there were no significant differences in them（ all P 〉 0. 05 ）. （4）The levels of IL-17 protein expression in prostate tissues in mild-, moderate- and severe-inflammation groups were all higher than those in control group and simple group （all P 〈 0.05 ）, and the expression level of IL-17 protein was positively correlated with the severity of BPH histological inflammation （r = 0. 501 ,P = 0. 014）. Conclusions Th1 and Th2 ceils may have little influence on BPH, while Th17 cell has elevated tendency, and IL-17 cytokine plasma content and its expression level in prostate tissues significantly increased. It is supposed that Th17 may be migrated to the prostate tissue by inflammation factors in prostate tissues, and thus promote the development of BPH.