青光眼患者Klotho与凋亡相关因子异常表达及其在小梁网氧化应激损伤预测中的作用

Prediction of oxidative stress injury of trabecular meshwork by abnormal expression of Klotho and apoptosis-related factors in glaucoma patients

目的研究青光眼患者Klotho蛋白、凋亡相关因子表达与小梁网组织氧化应激损伤的关系。方法选取我院于2021年10月至2023年10月收治的86例(86眼)青光眼患者为研究组,均于术中获取小梁网组织样本,另选取非眼部疾病患者小梁网供体组织样本(45例)为对照组。采用苏木精-伊红(HE)染色观察小梁网组织病理学特点,检测小梁网组织中Klotho蛋白、凋亡相关微粒蛋白(ASC)、半胱氨酸天冬氨酸蛋白酶1(Caspase-1)、超氧化物歧化酶(SOD)以及过氧化物酶(POD)表达水平。比较2组患者之间以及不同视野平均缺损程度青光眼患者Klotho蛋白、ASC蛋白、Caspase-1蛋白、SOD、POD表达水平,采用Pearson法分析青光眼患者Klotho蛋白、凋亡相关蛋白表达水平与小梁网氧化应激损伤的相关性。结果HE染色结果显示,研究组小梁网结构紊乱、板层交错,小梁束增厚,小梁细胞核固缩;对照组小梁网组织薄板以及小梁细胞束整齐排列,小梁细胞形态正常。研究组患者小梁网组织Klotho蛋白表达水平低于对照组,而ASC、Caspase-1蛋白表达水平均高于对照组(均为P<0.05)。不同严重程度患者Klotho蛋白、ASC蛋白、Caspase-1蛋白以及SOD、POD表达水平差异均有统计学意义(均为P<0.05)。随着疾病严重程度的增加,Klotho蛋白、SOD表达水平均呈明显降低趋势,而ASC蛋白、Caspase-1蛋白、POD表达水平呈明显增加趋势(均为P<0.05)。Pearson相关分析显示,小梁网组织Klotho蛋白与POD表达水平呈负相关,与SOD表达水平呈正相关,ASC、Caspase-1蛋白与POD表达水平均呈正相关,与SOD表达水平均呈负相关(均为P<0.05)。结论青光眼患者小梁网组织中Klotho低表达,而ASC、Caspase-1高表达,且表达水平与视野平均缺损程度呈相关性,可反映小梁网组织应激损伤程度。

Objective To investigate the relationship between the expression of Klotho,apoptosis-related factors and oxidative stress injury of the trabecular meshwork in patients with glaucoma.Methods Totally 86 patients(86 eyes)with glaucoma admitted to our hospital from October 2021 to October 2023 were selected as the study group.Tissue samples of trabecular meshwork were obtained during the operation.Trabecular meshwork donor tissues(45 cases)from patients with non-eye diseases were taken as the control group.Hematoxylin-Eosin(HE)staining was used to examine the histopathological characteristics,and the expression levels of Klotho,apoptosis-associated speck-like protein containing a CARD(ASC),cysteine-aspartic proteases-1(Caspase-1),superoxide dismutase(SOD)and peroxidase(POD)in trabecular meshwork tissues were detected.The expression levels of Klotho,ASC,Caspase-1,SOD and POD of patients in the two groups and those expression levels in glaucoma patients with different average visual field defects were compared.The correlation between expression levels of Klotho,apoptosis-related proteins and oxidative stress injury of the trabecular meshwork in glaucoma patients was analyzed by the Pearson method.Results HE staining results showed that the trabecular meshwork structure of patients in the study group was disorganized,with interlaced layers,thickened trabecular bundles and cell nucleus shrinkage,while the lamellas of trabecular meshwork tissues and trabecular cell bundles in the control group were orderly arranged,with normal forms of trabecular cells.In the study group,the expression level of Klotho in trabecular meshwork tissues was lower and the expression levels of ASC and Caspase-1 were higher than those of the control group(all P<0.05).There were statistically significant differences in the expression levels of Klotho,ASC,Caspase-1,SOD and POD in patients with different average visual field defects(all P<0.05).With the increase in disease severity,the expressions of Klotho and SOD showed a significant decrease,while the expressions of ASC,Caspase-1 and POD showed a significant increase(all P<0.05).Pearson correlation analysis showed that Klotho in the trabecular meshwork was negatively correlated with POD and positively correlated with SOD,while ASC and Caspase-1 were positively correlated with POD and negatively correlated with SOD(all P<0.05).Conclusion The expression of Klotho is low in the trabecular meshwork tissues of patients with glaucoma,while the expressions of ASC and Caspase-1 are high.These expressions are correlated with the average visual field defect,reflecting the stress injury degree of trabecular meshwork tissues.