纤维细胞和前列腺素E_2在Graves眼病发病机制中的作用研究

The Role of fibrocytes and prostaglandin E2in the pathogenesis Graves' ophthalmopathy

目的探讨纤维细胞和前列腺素E2在Graves眼病(GO)发病机制中的作用。方法收集湖北省武汉市华润武钢总医院眼科10例(10只眼)正常人、8例(8只眼)Graves病(GD)患者和11例(11只眼)Graves眼病(GO)患者的临床资料,将其分别分为正常对照组、GD组和GO组,观察炎性刺激对纤维细胞释放前列腺素E2(PGE2)的影响。采用单因素方差分析的方法,比较3组患者泪液PGE2浓度、血浆白细胞介素-1(IL-1)浓度和血液纤维细胞增殖水平。当差异有统计学意义时,3组之间进一步采用Bonferroni的方法进行两两比较;多组均数间比较采用ANOVA分析,两组均数间比较采用独立样本t检验。结果正常对照组患者泪液PGE2浓度为(35.36±8.12)pg/ml,GD组患者泪液PGE2浓度为(28.78±4.53)pg/ml,GO组患者泪液PGE2浓度为(142.63±12.45)pg/ml,差异有统计学意义(F=118.74,P<0.05)。GD组患者的泪液PGE2浓度与正常对照组比较,差异无统计学意义(t=1.36,P>0.05)。GO组患者的泪液PGE2浓度与正常对照组比较,差异有统计学意义(t=30.86,P<0.05)。GO组患者的泪液PGE2浓度与GD组比较,差异有统计学意义(t=28.79,P<0.05)。正常对照组患者血浆IL-1浓度为(32.56±7.27)pg/ml,GD组患者血浆IL-1浓度为(90.72±13.63)pg/ml,GO组患者血浆IL-1浓度为(108.78±15.67)pg/ml,差异有统计学意义(F=233.55,P<0.05)。GD组患者的血浆IL-1浓度与对照组比较,差异有统计学意义(t=39.76,P<0.05)。GO组患者的血浆IL-1浓度与对照组比较,差异有统计学意义(t=42.33,P<0.05)。GO组患者的血浆IL-1浓度与GD组比较,差异无统计学意义(t=4.04,P>0.05)。正常对照组患者血液纤维细胞增殖(1 254.34±645.23)个,GD组患者血液纤维细胞增殖(1 767.56±756.74)个,GO组患者血液纤维细胞增殖(5 340.67±867.43)个,差异有统计学意义(F=50.67,P<0.05)。GD组患者纤维细胞增生频率与对照组比较,差异无统计学意义(t=3.77,P>0.05)。GO组患者的纤维细胞增生频率与对照组比较,差异有统计学意义(t=55.34,P<0.05)。GO组患者的纤维细胞增生频率与GD组比较,差异有统计学意义(t=39.71,P<0.05)。加入IL-1组PGE2浓度为(24.78±7.62)ng/ml,而未加入IL-1组PGE2浓度为(0.05±0.05)ng/ml,差异有统计学意义(t=53.25,P<0.05),可见IL-1可显著增加纤维细胞PGE2的释放。结论 GO患者眶内组织肿胀和循环障碍可以刺激炎性因子的释放,从而增加纤维细胞的浸润并增加PGE2的释放;而PGE2可以通过增加血管的通透性而进一步加重GO。

Objective To investigate the putative role for fibrocytes and prostaglandin E2 in the pathogenesis of Graves＇ ophthalmopathy. Methods Ten healthy control subjects （10 eyes）, 8 patients （8 eyes） with Graves disease （GD） but without ophthalmopathy and 11 patients （11 eyes） with Graves＇ ophthalmopathy （GO） were recruited in the Department of Ophthalmology, Huarun-Wugang General Hospital. Concentrations of tear PGE2 , plasma IL-1 and capacities of circulating fibrocytes to proliferate and release PGE2 under IL-2 stimulation in vitro were comparatively assessed. Results The concentration of tear PGE2 was （35.36±8.12） pg/ml in control subjects,which was not different from （28.78±4.53） pg/ml in GD patients （ P〉0.05 ） but significantly lower than （ 142.63±12.45 ） pg/ml in GO patients （ P〈0.05 ）. The concentration of plasma IL-1b was sigaifieantly elevated in both GD （ 90. 72 ±13. 63 ） pg/ml and DO （108.78±15.67） pg/ml patients as compared with the control subjects （32.56±7.27） pg/ml, （P 〈0.05）. Invitro, circulating fibrocytes from GO patients showed a significantly higher proliferation rate than those from GD patients and control subjects （P〈0.05）, and IL-1 significantly increased fibrocyte production and release of PGE2. Conclusion Increased proliferation and PGE2 release fibrocytes in response to local inflammatory stimuli may be one of the mechanisms underlying the development of Graves＇ ophthalmopathy.