围绝经期干眼患者眼表CXCR3表达与性激素的相关性分析

Correlation between sex hormone and CXCR3 expression in ocular suface of perimenopausal female patients with xerophthalmia

目的本文通过分析围绝经期干眼患者和非围绝经期干眼患者血液中雌二醇(E2)、睾酮(T)、促黄体生产素(LH)表达水平的变化及CXCR3在结膜上皮细胞中的阳性表达率,探讨以E2、T、LH为代表的性激素与以CXCR3为代表的趋化因子受体家族的相关性及其在围绝经期干眼发病机制中的作用。方法选择干眼患者60例(120眼),分为围绝经期干眼组30例(60眼)及非围绝经期干眼组30例(60眼),分别进行泪液分泌试验、泪膜破裂时间、角膜荧光素染色检查,采用化学发光免疫法分别测定血清中E2、T、LH水平,采用结膜印迹细胞学的方法获取两组患者的结膜上皮细胞后,应用流式细胞术分析方法检测两组患者结膜上皮细胞中CXCR3的表达,比较两组性激素和CXCR3表达率的差异及CXCR3阳性表达的相关因素。结果围绝经期干眼组泪膜破裂时间为(2.90±1.37)s、基础泪液分泌值为(4.00±2.49)mm,均显著低于非围绝经期干眼组的(4.44±1.94)s和(6.67±2.69)mm(均为P<0.05);两组角膜荧光素染色评分值分别为(0.90±0.57)分和(1.00±1.32)分,组间相比差异无统计学意义(P>0.05)。围绝经期干眼组血清中E2为(28.22±32.34)μg·L-1、T为(13.68±14.12)ng·L-1,相对于非围绝经期干眼组的(40.39±39.51)μg·L-1和(20.84±1.16)ng·L-1均较低;LH水平为(25.47±14.53)mIU·L-1,较非围绝经期干眼组的(18.15±11.40)mIU·L-1高,但2组间3个指标的差异均无统计学意义。围绝经期干眼组CXCR3阳性率为(2.64±0.47)%,显著高于非围绝经期干眼组的(0.62±0.07)%(P<0.01)。CXCR3阳性率与泪膜破裂时间、基础泪液分泌值均呈显著的负相关(分别为r=-0.753、-0.684,均为P<0.05);CXCR3阳性率与E2、T、LH均呈不显著的正相关(分别为r=1.472、0.583、2.331,均为P>0.05)。结论围绝经期干眼患者性激素水平稍紊乱,E2与T降低,LH相对升高,三者与CXCR3阳性率不存在显著相关性。干眼的发病与趋化因子家族介导的炎性细胞浸润有密切关系。

Objective- To explore the correlation between sex hormone and the chemokine receptor family, and its role in pathogenesis of perimenopausal xerophthal- mia with the blood expression level of estradiol （ E2 ）, testosterone （T） and luteotropic hormone（LH） being representatives of the former, while CXCR3 being the representa- tive of the latter, by analyzing changes of the blood expression level of E2, T and LH and the positive rate of CXCR3 expression in conjunctival epithelial cells of patients with perimenopausal xerophthalmia and non-perimenopausal xerophthalmia. Methods Sixty patients（ 120 eyes） with xerophthalmia were selected,of which 30（ 60 eyes） were with perimenopausal xerophthalmia （ perimenopausal group ）, and 30 （ 50 eyes ） were with non-perimenopausal xerophthalmia（ non-perimenopausal group）. All patients were subjected to Schirmer I test,tear film break-up time（BUT） test and cornea fluorescein staining test. The level of E2, T and LH in blood serum was determined respectively u- sing chemiluminescent immunoassay. CXCR3 expression in conjunctival epithelial cells was measured using Flow Cytometry（FCM） after conjunctival epithelial cells of all the patients were obtained using conjunctival impression cytological means. Then differ- ences between sex hormone expressions and expression rates of CXCR3 of the two groups were found, and the correlative factors with CXCR3 positive expression of the two groups were also compared. Resultu Tear film BUT and basal tear secretion of perimenopausal group,which were（2.90 ± 1.37）s and（4.00 ±2.49） mm,were significantly lower than those of non-perimenopausal group, which were （4. 44 ± 1.94 ） s and （ 6.67 ± 2. 69 ） mm（ both P 〈 0.05 ）. No significant difference was present between evaluated values of cornea fluorescein staining of the two groups（0.90 ±0.57,1.00 ± 1.32） （P 〉0.05）. The level of E2, T in serum of perimenopausal group, which were（28.22 ± 32.34）μg ·L^-1 and （13.58 ± 14. 12）ng ·L^-1, were lower than those of non-perimenopausal group, which were（40.39 ±39.51） μg ·L^-1 and（20.84 ± 1.16）ng ·L^-1 ;While LH level in serum of peri- menopausal group, which was （25.47 ± 14.53 ） mIU ·L^-1, was higher than that of non-peri- menopausal group,which was（ 18. 15 ±11. 40 ） mIU ·L^-1 ,no significant difference was found between any of the three factors of the two groups. Positive rate of CXCR3 expres- sion of perimenopausal group, which was （ 2.54 ± 0. 47 ） % , was significantly higher than that of non-perimenopausal group, which was（0.52 ± 0.07 ） % （P 〈0.01 ）. Significant nega- tive correlations existed between positive rate of CXCR3 expression and two factors（ tear film BUT, basal tear secretion） （r = -0.753, -0.684 ;both P 〈 0.05 ）. Non-significant posi- tive correlations existed between positive rate of CXCR3 expression and three factors （ E2, T and LH level） （ r = 1. 472,0. 583,2. 331 ; all P 〉 0. 05 ）. Conclusion Levels of sex hormones in patients with perimenopausal xerophthalmia are slightly disordered, with E2 level and T level lower, while LH level rises. No significant correlation exists between any of the three factors and positive rate of CXCR3 expression. There is a close association between pathogenesis of xerophthalmia and infiltration of inflammatory cells guided by chemoldne receptor family.