芳香化酶抑制剂相关骨关节症状的免疫调节机制研究

目的　探讨乳腺癌患者应用芳香化酶抑制剂（ＡＩｓ）所致骨关节症状的免疫调节机制。方法　选择Ⅰ ～Ⅲ期绝经后乳腺癌患者５１例，３３例应用ＡＩｓ治疗，分为有较严重骨关节症状组１６例（ＢＰＩ-ＳＦ疼痛评分＞７）和未出现骨关节症状组１７例，另１８例为未进行ＡＩｓ治疗受体阴性组。同时设对照组（健康人）１６例。取各组研究对象的外周血，检测血中雌激素（Ｅ２）水平；应用ＥＬＩＳＡ方法检测血清中ＩＦＮ-γ、ＩＬ-４浓度以及骨钙素（ＢＧＰ）、骨碱性磷酸酶（ＢＡＬＰ）和Ⅰ型胶原羧基端前肽（ＣＩＣＰ）的浓度；应用流式细胞仪检测ＣＤ４＋ＣＤ２５＋调节性Ｔ细胞表达率。结果　有症状组的Ｅ２水平为（７２.８±５８.９）ｐｍｏｌ／Ｌ，无症状组为（６７.４±５７.６）ｐｍｏｌ／Ｌ，均低于对照组的（２０６.９±１１９.４）ｐｍｏｌ／Ｌ（Ｐ＜０.０１），但有症状组与无症状组之间差异无统计学意义（Ｐ＞０.０５）。有症状组的ＩＦＮ-γ浓度为（８２.８３±５.５３）ｐｇ／ｍｌ，明显高于无症状组和受体阴性组（Ｐ＜０.０５）；有症状组的ＩＬ-４浓度为（２２.８３±１.０９）ｐｇ／ｍｌ，低于无症状组和受体阴性组（Ｐ＜０.０５）。流式细胞仪检测结果显示，有症状组外周血ＣＤ４＋ＣＤ２５＋Ｔ细胞的表达率为（５.６±１.１）％，低于无症状组的（１２.１±２.３）％和受体阴性组的（１４.９±３.５）％，差异均有统计学意义（Ｐ＜０.０１）。有症状组的骨代谢指标ＢＡＬＰ和ＣＩＣＰ水平分别为（６２.１±５.５）Ｕ／Ｌ和（１５６.８±４１.１）ｎｇ／ｍｌ，均高于无症状组的（４５.２±４.６）Ｕ／Ｌ和（１３７.５±３６.９）ｎｇ／ｍｌ，差异有统计学意义（Ｐ＜０.０５），但有症状组的ＢＧＰ水平与无症状组无明显差异（Ｐ＞０.０５）。结论　应用ＡＩｓ产生的相关骨关节症状可能与患者机体的免疫功能调节异常密切相关，其确切机制有待进一步的研究阐明。

Immunoregulation mechanism of patients with aromatase inhibitors-related musculoskeletal symptoms

Objective To investigate immunoregulation mechanism of patients with aromatase inhibitors-related musculoskeletal symptoms（AIMSS）.Methods A total of 51 postmenopausal women with stage Ⅰ-Ⅲ breast cancer were enrolled.These patients were divided into three groups： 16 patients with AIMSS were in symptom group;17 patients who received aromatase inhibitors（AIs） without AIMSS were in no symptom group;18 patients who didn＇t receive AIs because of their negative ER and PR receptors were in receptor negative group.In addition,16 healthy persons were enrolled in control group.The peripheral blood samples of subjects in each group were obtained.The blood level of estrogen was tested.The levels of serum cytokines（INF-γ and IL-4） were measured using cytokine specific enzyme-linked immunosorbent assay kits.Percentage of CD4＋CD25＋regulatory T cell（Treg cell） in peripheral blood was determined by flow cytometry.The bone gla protein（BGP）,bone alkaline phosphatase（BALP） and Ⅰ collagen carboxyl-terminal propeptide（CICP） of bone metabolism were detected.Results Compared with control group,the level of E2 in symptom group was（72.8±58.9）pmol/L and no symptom group was（67.4±57.6） pmol/L,which were significantly lower than that in control group（P0.01）.But there was no statistical difference of E2 levels between symptom group and no symptom group.Compared with no symptom group,the concentration level of IFN-γ（82.83±5.53）pg/ml was significantly higher（P0.01）,and the concentration level of IL-4（22.83±1.09）pg/ml was lower in symptom group（P0.05）.Compared with control group and receptor negative group,the concentration level of INF-γ in symptom group was higher（P0.05）,while concentration level of IL-4 was lower（P0.05）.Treg cell expressional percentage（5.6±1.1）% in symptom group decreased significantly than that（12.1±2.3）% in no symptom group and that（14.9±3.5）% in receptor negative group（P0.01）.The concentration level of BALP and CICP were（62.1±5.5） U/L and（156.8±41.1）ng/ml in symptom group,which was higher than that（45.2±41.1）U/L,（137.5±36.9）ng/ml in no symptom group（P0.05）.Conclusion AIMSS may be closely related to aberrant immunoregulation of patients,which needs to be confirmed in further studies.