甲状腺相关眼病眼眶组织透明质酸合成酶表达的研究

Expression of hyaluronan synthase messenger ribonucleic acids in orbital tissues of patients with thyroid-associated ophthalmopathy

目的探讨透明质酸合成酶2(HAS2)mRNA在甲状腺相关眼病(TAO)患者球后脂肪组织及眼外肌中的表达。方法收集四川大学华西医院眼科2000—2005年确诊并行眼眶减压术或斜视矫正术的TAO患者21例为TAO组,获得眼外肌标本18个,脂肪标本17个;Ⅱ期义眼台植入患者、眼袋整形者及共同性斜视患者18例作为对照组,共获得眼外肌组织标本17个,脂肪组织标本11个。所有标本通过原位杂交的方法,测量吸光度(A)值,计算HAS2mRNA的表达。依据活动期的临床表现对TAO患者进行临床活动性评分(CAS),采用Spearman秩相关分析对HAS2mRNA在待测眼组织标本中的表达量与TAO患者CAS的相关性进行评估。结果 TAO组患者眼外肌和脂肪间质组织HAS2明显黄染,对照组均呈轻度黄染。TAO组和对照组的眼外肌组织中HAS2mRNAA值分别为191.133±48.898和133.200±48.933,差异有统计学意义(P=0.001)(95%CI:24.275～91.590);TAO组和对照组眶脂肪组织中HAS2mRNAA值分别为50.430±26.812和33.048±11.690,差异有统计学意义(t=2.350,P=0.028)(95%CI:2.099～32.664);CAS与TAO脂肪组织中HAS2mRNA的表达无明显相关性(r=0.044,P=0.868),与肌肉组织中HAS2mRNA的表达呈弱正相关性(r=0.496,P=0.036)。结论 TAO患者HAS2mRNA的高表达是造成眶后透明质酸堆积的原因之一。

Background Thyroid-associated ophthalmopathy （TAO） is a noninfectious,inflammatory disorder of the orbit mostly associated with hyperthyroidism.Hyaluronic acid （HA） accumulations in orbital tissue plays an important role in pathogenesis of TAO.Hyaluronic acid synthesis is related to hyaluronan synthase （HAS）.Objective The aim of this study was to investigate the expression of hyaluronan synthase 2 （HAS2） mRNA in thyroid-associated ophthalmopathy （TAO）.Methods Twenty-one patients with TAO were collected.The TAO was confirmed in West China Hospital from 2000 to 2005.Eighteen patients without TAO were used as controls.The extraocular muscle tissue samples and adipose tissue samples were obtained from TAO patients and control subjects during the operation.Expression of HAS2 mRNA in the samples was detected by in situ hybridization method and the mean absorbance value （A） between TAO group and control group.The clinical activity scores of TAO patients was taken based on the classical signs of inflammation.The correlation of expression of HAS2 mRNA in the samples with clinical activity scores of TAO patients was evaluated.This study process was approved by Ethical Committee of West China Hospital of Sichuan University and the written informed consent was obtained from each subject at the initial of the medical plan.Results The extraocular muscle tissue and adipose tissue showed the stronger yellow staining for HAS2 in TAO group,but the weak staining was seen in control group.The mean A values of HAS2 mRNA in muscle tissue samples of experimental group was （191.133±48.898） and was significantly higher than that of control group （133.200±48.933） （t=3.502,P=0.001） with 95% confidence interval 24.275-91.590.The mean A values of HAS2 mRNA in adipose tissue samples of experimental group was （50.430±26.812）and was significantly higher than that of control group （33.048±11.690）（t=2.350,P=0.028）with 95% confidence interval 2.099-32.664.No significant correlation was found in the expression of HAS2 mRNA on extraocular muscle tissue with clinical score in TAO patients （r=0.496,P=0.036）,and the weak positive correlation was seen in the expression of HAS2 mRNA on adipose tissue with clinical activity score in TAO patients（r=0.044,P=0.868）.Conclusion The higher expression of HAS2 mRNA is one of the reasons why hyaluronic acid aggregate in posterior orbital tissue in TAO patients.