摘要
背景干眼是一种多因素影响的泪膜和眼表疾病，免疫炎症反应在干眼的发病中起至关重要的作用。非甾体类抗炎药物通过抑制环氧合酶通路，具有抑制眼部炎症和免疫调节的作用，是一种潜在的抗干眼药物。目的研究非甾体类抗炎药物质量分数0．1％普拉洛芬滴眼液治疗中重度干眼的临床疗效，并探讨其作用机制。方法采用随机对照研究设计。对按标准纳人的中重度干眼患者30例按照随机数字表法随机分为试验组及对照组，均取右眼为试验眼。试验组15例15眼，给予0．1％普拉洛芬滴眼液和质量分数0．1％玻璃酸钠滴眼液联合用药；对照组15例15眼基线特征与试验组匹配，单独使用0．1％玻璃酸钠滴眼液。用药前和用药2周时进行临床和实验室指标检测。临床检测指标包括眼表疾病指数（OSDI）、泪膜破裂时间（BUT）、泪液分泌试验I（SchirmerI试验）、眼表染色（OSS）评分。实验室检测通过结膜印迹细胞学方法获取球结膜上皮细胞，应用流式细胞术检测球结膜上皮细胞中人类白细胞DR抗原（HLA—DR）及CDllb的表达。结果试验组和对照组患者的年龄、性别构成比的差异均无统计学意义（t=0．412，P：0．684；，=0．240，P=0．624），两组间各项临床和实验室指标实测值的比较差异均无统计学意义（P〉0．05）。用药2周时，试验组受试者OSDI、OSS评分和球结膜上皮细胞中HLA—DR抗原表达明显低于对照组，而BUT均明显长于对照组，差异均有统计学意义（t=2．43，P=0．03；t=2．83，P=0．01；t=3．29，P=0．00；t=3．23，P=0．00），两组受试者的SchirmerI试验和结膜上皮细胞CDllb表达量用药2周后对比差异均无统计学意义（t=0．17，P=0．87；t=0．28，P=0．79）。试验组用药2周和用药前相比，OSDI、OSS评分和BUT较用药前均明显改善，球结膜上皮细胞中HLA．DR抗原表达量降低，差异均有统计学意义（t=12．30、10．70、6．10、7．92，P：0．00）；对照组用药前后各项指标差异均无统计学意义（P〉0．05）。试验组用药2周结膜上皮细胞HLA—DR抗原表达量与OSDI和OSS评分均呈正相关（r=0．601，P=0．018；r=0．586，P=0．022），与BUT间呈负相关（r=-0．697，P：0．004）。结论0．1％普拉洛芬滴眼液联合0．1％玻璃酸钠滴眼液用药短期内可有效缓解中重度干眼的症状和体征，其作用机制与降低眼表免疫炎症标志物HLA—DR抗原的表达相关。
Background Dry eye is a multi-factorial-induced tear film and ocular surface disorder. Immuno- inflammation plays a key role in the pathogenesis of dry eye. As inhibitor of the cyelo-oxygenase pathway,nonsteroidal anti-inflammatory drugs play an anti-inflammatory and anti-hypersensitivity role,and it can be a potential treatment for dry eyes. Objective This study was to investigate the effectiveness of nonsteroidal anti-inflammatory drugs （0. 1% topical pranoprofen） on moderate to severe dry eyes and its mechanism. Methods This was a small sample of randomized controlled clinical trial. Thirty right eyes of 30 patients with moderate to severe dry eyes were included in the study according to the diagnosis criteria and randomized into two groups. The patients of the trial group received topical administration of 0. 1% pranoprofen plus 0. 1% sodium hyaluronate, and those of the control group received the topical 0. 1% sodium hyaluronate only. Ocular surface inflammation index scores （OSDI） and ocular surface fluorescine staining （OSS） scores were measured under the slit lamp,and tear film break-up time （BUT） ,Schirmer I test values were evaluated. The expression of human leucocyte antigen-DR （HLA-DR） and CDllb in conjunctiva epithelial ceils were detected by impression cytology and flow cytometry （ FCM ）. All the indexes were compared between the two groups before and after treatment. Informed consent was obtained from all patients. Results There were no significant differences in terms of age and gender and their baseline values between the trial group and control group （ t = 0. 412, P = 0. 684 ;X2 = 0. 240, P = 0. 624 ） , and so were all the indexes （ P 〉 0.05 ）. Compared with the control group,the OSDI, OSS scores and cells positive for HLA-DR were lowered but the BUT was delayed in the trial group on day 15 （t=2.43,P=O. O3;t=2.83,P=O. O1;t=3.29,P=O. OO;t=3.23,P=O. O0）. No significant differences were found in the Schirmer I test value and CDllb expression between these two groups （t = 0. 17, P = 0.87 ;t = 0. 28, P = 0. 79 ）. The OSDI, OSS scores and BUT were significantly improved, and the number of cells positive for HLA-DR were reduced 15 days after administration of drugs in comparison with before treatment in the trial group （t = 12.30,10.70,6.10,7.92,P = 0.00）. However, there were no comparable alteration seen in these indexes before and after the usage of drugs in the control group （P〉0.05）. Positive correlations were found in HLA- DR expression with OSDI and OSS （r=0. 601 ,P=0. 018;r=0. 586,P=0. 022） and a negative correlation in HLA- DR expression with BUT （r=-0.697,P=0.004） on day 15 in the trial group. Conclusions Topical usage of 0. 1% pranoprofen is beneficial for remitting the ocular signs and symptoms in moderate to severe dry eyes. This study illustrates that topical usage of 0. 1% pranoprofen can down-regulate the expression of inflammatory markers in conjunctival epithelial cells.
出处
《中华实验眼科杂志》
CAS
CSCD
北大核心
2012年第5期445-449,共5页
Chinese Journal Of Experimental Ophthalmology
基金
国家自然科学基金项目（30600692、81070755）
关键词
干眼
免疫诱导炎症反应
人类白细胞DR抗原
非甾体类抗炎药
随机对照试验
Dry eye
Immuno-induced inflammation
Human leucocyte antigen-DR
Nonsteroidal anti- inflammatory drug
Randomized controlled trial
