Liu Dan, Cheng Chuchu, Zhou Lan, Zeng Qiqiao, Zi Tao, Chen Gongyi, Sun Hongyan, Li Cunzi, Wang Jun, Yang Ming-Ming
Department of Ophthalmology, The Second Clinical Medical College, Jinan University, Shenzhen, China.
Department of Endocrinology, The Second People's Hospital of Futian District, Shenzhen, China.
PLoS One. 2024 Dec 2;19(12):e0312452. doi: 10.1371/journal.pone.0312452. eCollection 2024.
This study aims to explore glucose-6-phosphate dehydrogenase (G6PD) activity in diabetic retinopathy (DR) and its correlation with inflammatory factors, elucidating the regulatory role of G6PD in DR pathology.
A total of 151 T2DM patients were divided into three groups: diabetes without retinopathy (DNR, n = 59), non-proliferative retinopathy (NPDR, n = 46) and proliferative retinopathy (PDR, n = 49). Plasma G6PD activity was measured by a Randox G6PD kit and compared between these groups. Then the G6PD activity was correlated with inflammatory cytokines and metabolic parameters in these patients. A STZ-induced diabetic rat model was established, G6PD activity was validated by western blot and immunofluorescence staining in the retina of this model.
Plasma G6PD activity decreased in the order of DNR, NPDR and PDR groups (P<0.01). G6PD activity was negatively correlated with IL-6, IL-8, TNF-α, cholesterol, and LDL (r = -0.1625, -0.1808, -0.1865, -0.1747, r = -0.1807, P<0.05). Multiple regression analysis showed TNF-α, IL-6, and LDL were independent related factors for G6PD. Logistic regression analysis showed G6PD, triglyceride, cholesterol, IL-8, TNF-α, and macular edema were influencing factors for T2DM with DR. Western Blot analysis indicated a significant reduction of G6PD expression in the retina, and immunofluorescence staining showed distribution of G6PD especially in the retinal endothelium cell decreased.
G6PD may play an important role in DR occurrence and progression, with decreased expression correlating closely with lipid metabolism and inflammatory factors.
本研究旨在探讨糖尿病视网膜病变（DR）中葡萄糖-6-磷酸脱氢酶（G6PD）的活性及其与炎症因子的相关性，阐明G6PD在DR病理过程中的调节作用。
将151例2型糖尿病患者分为三组：无视网膜病变糖尿病组（DNR，n = 59）、非增殖性视网膜病变组（NPDR，n = 46）和增殖性视网膜病变组（PDR，n = 49）。采用朗道G6PD试剂盒检测血浆G6PD活性，并在这些组之间进行比较。然后将这些患者的G6PD活性与炎症细胞因子和代谢参数进行相关性分析。建立链脲佐菌素诱导的糖尿病大鼠模型，通过蛋白质免疫印迹法和免疫荧光染色法验证该模型视网膜中的G6PD活性。
血浆G6PD活性按DNR组、NPDR组和PDR组的顺序降低（P<0.01）。G6PD活性与白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、肿瘤坏死因子-α（TNF-α）、胆固醇和低密度脂蛋白（LDL）呈负相关（r = -0.1625、-0.1808、-0.1865、-0.1747、r = -0.1807，P<0.05）。多元回归分析显示TNF-α、IL-6和LDL是G6PD的独立相关因素。逻辑回归分析显示G6PD、甘油三酯、胆固醇、IL-8、TNF-α和黄斑水肿是2型糖尿病合并DR的影响因素。蛋白质免疫印迹分析表明视网膜中G6PD表达显著降低，免疫荧光染色显示G6PD的分布，尤其是在视网膜内皮细胞中的分布减少。
G6PD可能在DR的发生和发展中起重要作用，其表达降低与脂质代谢和炎症因子密切相关。
