miRNA-15b和成纤维细胞生长因子2(FGF2)在增生型糖尿病视网膜病变患者玻璃体及视网膜增生膜组织中的表达

目的　探讨增生型糖尿病视网膜病变（PDR）患者玻璃体、视网膜增生膜组织中miRNA-15b（miR-15b）和成纤维细胞生长因子2（FGF2）的表达情况，并进行相关性研究，初步探讨PDR发生原因。方法　选取2016年9月至2019年10月期间在重庆市开州区人民医院眼科住院的PDR患者80例（80眼）作为PDR组，收集其玻璃体及视网膜增生膜组织；选取同期因眼外伤在本院眼科行眼球摘除术的2型糖尿病患者21例（21眼）作为对照组，收集其玻璃体及视网膜组织；通过实时荧光定量聚合酶链式反应（qRT-PCR）法检测玻璃体及视网膜组织/视网膜增生膜组织中miR-15b水平，分别通过酶联免疫吸附法（ELISA）、Western blot法检测玻璃体、视网膜组织/视网膜增生膜组织中FGF2蛋白水平表达；通过Pearson相关性分析法分析对照组玻璃体及视网膜组织以及PDR组患者玻璃体及视网膜增生膜组织中miR-15b与FGF2水平相关性；通过二元Logistic回归分析影响糖尿病患者发生PDR的危险因素。结果　PDR组糖尿病病程显著长于对照组（P<0.001）。PDR组玻璃体及视网膜增生膜组织中miR-15b相对表达量分别为0.52±0.07和0.76±0.12，均显著低于对照组（1.03±0.19和1.14±0.19），差异均有统计学意义（均为P<0.001）；PDR组玻璃体及视网膜增生膜组织中FGF2蛋白表达水平分别为（17.65±4.23）ng·L^-1和0.92±0.23，均显著高于对照组［（12.13±3.05）ng·L^-1和0.61±0.15，均为P<0.001）］。对照组玻璃体、视网膜组织中miR-15b与FGF2蛋白表达水平均无相关性（均为P>0.05）；PDR组玻璃体、视网膜增生膜组织中miR-15b与FGF2蛋白表达水平均呈显著负相关（r=-0.708、-0.705，均为P<0.05）；二元Logistic回归分析结果显示，糖尿病病程长及玻璃体、视网膜增生膜组织中miR-15b水平低、FGF2蛋白表达水平高是影响糖尿病患者发生PDR的危险因素（均为P<0.01）。结论　玻璃体及视网膜增生膜组织中miR-15b与FGF2蛋白表达水平与PDR的发生密切相关。

Expression and significance of microRNA-15b and fibroblast growth factor 2 in vitreous humor and retinal proliferative membrane tissues of patients with proliferative diabetic retinopathy

Objective　To investigate the expression of microRNA-15b (mir-15b) and fibroblast growth factor 2 (FGF2) in vitreous humor and retinal proliferative membrane tissues of patients with proliferative diabetic retinopathy (PDR), followed by correlation study being carried out to explore the causes of PDR.Methods　Together 80 PDR patients (80 eyes) in the Ophthalmology Department of Kaizhou District People’s Hospital of Chongqing from September 2016 to October 2019 were selected as the PDR group, and their vitreous fluid and retinal proliferative membrane tissues were collected; 21 patients (21 eyes) with type 2 diabetes who underwent eye enucleation due to ocular trauma in the ophthalmology department of our hospital during the same period were selected as the control group, and their vitreous fluid and retinal proliferative membrane tissue were also collected. The level of miR-15b in vitreous humor and retinal tissue/retinal proliferative membrane tissues was detected by real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) method, the level of FGF2 protein in vitreous humor, retinal tissue/retinal hyperplasia membrane tissue was detected by enzyme-linked immunosorbent assay (ELISA) and Western blot, respectively; the correlation between miR-15b and FGF2 levels in the vitreous humor and retinal tissue of the control group and the vitreous humor and retinal proliferative membrane tissues of the PDR patients was analyzed by Pearson method; and the risk factors of PDR in diabetic patients were analyzed by binary logistic regression.Results　The course of diabetes in the PDR group was significantly longer than that in the control group (P<0.05); the levels of miR-15b in vitreous humor and retinal proliferative membrane tissues in the PDR group were significantly lower than those in the control group ［(0.52±0.07) vs. (1.03±0.19), (0.76±0.12) vs. (1.14±0.19), both P<0.05］, but the level of FGF2 protein was significantly higher than those in the control group ［(17.65±4.23) ng·L^-1 vs. (12.13±3.05) ng·L^-1, (0.92±0.23) vs. (0.61±0.15), both P<0.05)］. There was no correlation between the expression levels of miR-15b and FGF2 in vitreous humor and retinal tissues of the control group (both P>0.05). The expression levels of miR-15b and FGF2 in the vitreous humor and retinal proliferative membrane tissues of PDR patients were negatively correlated (r= -0.708, -0.705, both P<0.05). Binary Logistic regression showed that long course of diabetes, low levels of miR-15b in vitreous humor and retinal proliferative membrane tissues, and high levels of FGF2 in vitreous humor and retinal proliferative membrane tissues were risk factors that affected PDR in diabetic patients (all P<0.01).Conclusion　The levels of miR-15b and FGF2 in vitreous humor and retinal proliferative membrane tissues are closely related to the occurrence of PDR.