糖尿病视网膜病变患者血清中HIF-1α、MMP-1、MMP-2含量与病变分期及血管生成的关系

Correlation of serum hypoxia-inducible factor-1α,matrix metalloproteinase-1 and matrix metalloproteinase-2 levels of diabetic retinopathy patients with the severity of diabetic retinopathy and angiogenesis

目的 探讨糖尿病视网膜病变(DR)患者血清中缺氧诱导因子-1α(HIF-1α)、基质金属蛋白酶(MMP)-1和MMP-2含量与病变分期及血管生成的关系。方法 选取2020年12月至2021年12月于本院住院治疗的280例2型糖尿病(T2DM)无DR患者,作为T2DM组;选取同期于本院眼科住院治疗的276例DR患者,作为DR组;另选取于本院体检的健康受试者282例,作为正常组。正常组、T2DM组、DR组受试者性别构成和年龄差异均无统计学意义(均为P>0.05)。根据眼底检查及荧光素眼底血管造影结果将DR组患者进一步分为非增生型糖尿病视网膜病变(NPDR)组129例及增生型糖尿病视网膜病变(PDR)组147例。比较正常组、T2DM组和DR组以及NPDR组和PDR组受试者空腹血糖(FPG)、糖化血红蛋白(HbA1c)及血清HIF-1α、MMP-1、MMP-2含量;比较正常组、T2DM组和DR组以及NPDR组和PDR组受试者血清碱性成纤维细胞生长因子(bFGF)、促血管生成素-1(Ang-1)、血管内皮生长因子(VEGF)含量;采用Pearson相关性分析法分析DR患者血清HIF-1α、MMP-1、MMP-2与bFGF、Ang-1、VEGF含量的相关性。结果 T2DM组、DR组患者FPG、HbA1c及血清HIF-1α、MMP-1、MMP-2含量均高于正常组,差异均有统计学意义(均为P<0.05)。DR组患者血清HIF-1α、MMP-1、MMP-2含量均高于T2DM组,差异均有统计学意义(均为P<0.05);两组患者FPG、HbA1c比较,差异均无统计学意义(均为P>0.05)。PDR组患者血清HIF-1α、MMP-1、MMP-2含量均高于NPDR组,差异均有统计学意义(均为P<0.05);两组患者FPG、HbA1c比较,差异均无统计学意义(均为P>0.05)。T2DM组和DR组患者血清bFGF、Ang-1、VEGF含量均高于正常组,差异均有统计学意义(均为P<0.05);DR组患者血清bFGF、Ang-1、VEGF含量均高于T2DM组,差异均有统计学意义(均为P<0.05)。PDR组患者血清bFGF、Ang-1、VEGF含量均高于NPDR组,差异均有统计学意义(均为P<0.05)。Pearson相关性分析结果显示,DR患者HIF-1α、MMP-1、MMP-2与bFGF、Ang-1、VEGF含量均呈正相关(均为P<0.05)。结论 DR患者血清HIF-1α、MMP-1、MMP-2含量异常升高,且与DR进展及血管生成密切相关,可对疾病发展趋势进行预测,从而指导临床干预。

Objective To investigate the expression of hypoxia-inducible factor-1α(HIF-1α),matrix metalloproteinase(MMP)-1 and MMP-2 in the serum of patients with diabetic retinopathy(DR),and to analyze their relationship with the stage of DR and angiogenesis.Methods A total of 280 patients with type 2 diabetes mellitus(T2DM)and no DR who were hospitalized in our hospital from December 2020 to December 2021 were selected as the T2DM group;276 DR patients who were hospitalized in the ophthalmology department of our hospital during the same period were selected as the DR group;another 282 healthy subjects who underwent physical examination in our hospital were selected as the normal group.There were no significant differences in gender and age distribution among the normal group,T2DM group and DR group(both P>0.05).According to the results of fundus examination and fluorescein angiography,the patients in the DR group were divided into non-proliferative diabetic retinopathy(NPDR)group(129 patients)and proliferative diabetic retinopathy(PDR)group(147 patients).The fasting plasma glucose(FPG),glycosylated hemoglobin(HbA1c)and serum HIF-1α,MMP-1,MMP-2 levels of subjects in the normal group,T2DM group and DR group,as well as NPDR group and PDR group were compared.The serum basic fibroblast growth factor(bFGF),angiopoietin-1(Ang-1)and vascular endothelial growth factor(VEGF)levels of subjects in the normal group,T2DM group and DR group,as well as NPDR group and PDR group were compared.Pearson correlation analysis was used to analyze the correlation between serum HIF-1α,MMP-1,MMP-2 and bFGF,Ang-1,VEGF levels in DR patients.Results The FPG,HbA1c and serum HIF-1α,MMP-1,MMP-2 levels of the T2DM group and DR group were higher than those of the normal group,and the differences were statistically significant(all P<0.05).The serum HIF-1α,MMP-1 and MMP-2 levels of the DR group were significantly higher than those of the T2DM group(all P<0.05);there were no significant differences in FPG and HbA1c between the two groups(both P>0.05).The serum HIF-1α,MMP-1 and MMP-2 levels of the PDR group were significantly higher than those of the NPDR group(all P<0.05);there were no significant differences in FPG and HbA1c between the two groups(both P>0.05).The serum bFGF,Ang-1 and VEGF levels of the T2DM group and DR group were higher than those of the normal group,and the differences were statistically significant(all P<0.05).The serum bFGF,Ang-1 and VEGF levels of the DR group were significantly higher than those of the T2DM group(all P<0.05).The serum bFGF,Ang-1 and VEGF levels of the PDR group were significantly higher than those of the NPDR group(all P<0.05).Pearson correlation analysis showed that HIF-1α,MMP-1 and MMP-2 were positively correlated with bFGF,Ang-1 and VEGF levels in DR patients(all P<0.05).Conclusion The serum HIF-1α,MMP-1 and MMP-2 levels of DR patients are abnormally elevated,and are closely related to the progression of DR and angiogenesis.These parameters can be used to predict the disease development trend and guide clinical intervention.