青光眼术后干眼患者泪液中MAPK、Sirt1水平与泪膜功能的相关性分析

Correlations between MAPK,Sirt1 levels in lacrimal gland and tear film function in dry eye patients after glaucoma surgery

目的分析青光眼术后干眼患者泪液中丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)、沉默信息调节因子相关酶1(silent information regulator of transcription1,Sirt1)水平与泪膜功能的关系。方法选择2015年9月到2017年12月在我院确诊的青光眼小梁切除术后干眼患者50例(50眼)为干眼组,选择同期行青光眼小梁切除术后未并发眼部疾病的患者50例(50眼)为对照组。采用Western blot检测两组患者泪液中p38MAPK、p-p38MAPK、JNK、p-JNK、ERK1/2、p-ERK1/2和Sirt1的蛋白表达水平;RT-PCR检测两组患者泪液中p38MAPK、JNK、ERK1/2和Sirt1 mRNA表达水平;检测两组患者泪膜破裂时间(BUT)、泪液分泌试验(Schirmer I test,SIt)和角膜荧光素染色(fluorescence staining,FL)评分;采用Pearson相关性分析各蛋白表达水平与泪膜功能之间的相关性。结果与对照组相比,干眼组患者泪液中p-p38MAPK、p-JNK、p-ERK1/2蛋白表达水平均显著增加(均为P<0.05),Sirt1蛋白和mRNA的表达水平均显著下降(均为P<0.05),p38MAPK、JNK和ERK1/2 mRNA的表达水平差异均无统计学意义(均为P>0.05),BUT和SIt均显著下降(均为P<0.001),FL评分显著升高(P<0.001)。干眼组患者泪液中p-p38MAPK、p-JNK、p-ERK1/2蛋白表达水平与BUT和SIt均呈显著负相关,与FL评分呈显著正相关(均为P<0.001);泪液中Sirt1蛋白表达水平与BUT和SIt均呈显著正相关,与FL评分呈显著负相关关系(均为P<0.001)。结论青光眼术后干眼患者泪液中MAPK、Sirt1水平与泪膜功能显著相关。

Objective To analyze the relationship between mitogen-activated protein kinase(MAPK),silment information regulator factor related enzymes 1(Sirt1)in lacrimal gland and tear film function in dry eye patients after glaucoma surgery.Methods A total of 50 dry eye patients after glaucoma surgery who were confirmed in our hospital from September 2015 to December 2017 were enrolled as dry eye group.Another 50 patients who were not complicated with ocular disease after glaucoma trabeculectomy in the same period were enrolled as control group.Western blot was used to detect the protein expression levels of p38MAPK,p-p38MAPK,JNK,p-JNK,ERK1/2,p-ERK1/2 and Sirt1 in the tears of the two groups of patients.RT-PCR was used to detect the expression levels of p38MAPK,JNK,ERK1/2 and Sirt1mRNA in the tears of the two groups of patients.The break-up time(BUT),Schirmer I test(SIt)and fluorescein staining(FL)score in both groups were detected.Pearson correlation analysis was performed to analyze correlation between above proteins and tear film function.Results Compared with control group,expression levels of p-p38MAPK,p-JNK and p-ERK1/2 in tears of dry eye group after glaucoma surgery were significantly up-regulated(all P<0.05),while expression levels of Sirt1 mRNA and protein were significantly down-regulated(all P<0.05),and there was no significant difference in the expression levels of p38MAPK,JNK and ERK1/2 mRNA(all P>0.05);BUT and SIt were significantly decreased(both P<0.001),and FL score was significantly increased(P<0.001).The expression level of p-p38MAPK,p-JNK and p-ERK1/2 in tears of dry eye group was significantly negatively correlated with BUT and SIt(all P<0.001),while significantly positively correlated with FL score(all P<0.001).The expression level of Sirt1 in tears was significantly positively correlated with BUT and SIt(both P<0.001),while significantly negatively correlated with FL score(P<0.001).Conclusion The levels of MAPK and Sirt1 in tears of dry eye patients after glaucoma surgery are significantly correlated with tear film function.