视网膜静脉阻塞患者血清微小RNA表达水平与黄斑水肿程度的相关性

doi:10.11958/20252948

摘要/Abstract

摘要：

目的探究视网膜静脉阻塞（RVO）患者血清miR-155-5p、miR-17-5p、miR-375表达水平与黄斑水肿（ME）程度的相关性。方法选取2020年1月—2024年11月我院收治的RVO并发ME患者103例为观察组，按照ME程度将RVO并发ME患者分为轻度47例、中度34例、重度22例，根据预后情况分为不良组38例和良好组65例。另选取同期本院的单纯RVO患者103例作为对照组，检测对照组与观察组血清miR-155-5p、miR-17-5p、miR-375水平。Spearman相关分析血清miR-155-5p、miR-17-5p、miR-375与ME程度的相关性。Logistic回归分析RVO并发ME患者预后的影响因素；受试者工作特征（ROC）曲线分析血清miR-155-5p、miR-17-5p、miR-375对RVO并发ME患者预后的预测价值。结果与对照组相比，观察组血清miR-155-5p、miR-17-5p水平升高，miR-375水平降低（P<0.05）。随着ME程度增加，血清miR-155-5p、miR-17-5p水平依次升高，miR-375水平依次降低（P<0.05）。RVO并发ME患者病情与血清miR-155-5p、miR-17-5p呈正相关（r_s分别为0.536、0.524，均P<0.05），与血清miR-375呈负相关（r_s=-0.488，P<0.05）。与良好组相比，不良组血清miR-155-5p、miR-17-5p水平升高，miR-375水平降低（P<0.05）。miR-155-5p升高、miR-17-5p升高、miR-375降低是影响RVO并发ME患者预后不良的危险因素（P<0.05）。血清miR-155-5p、miR-17-5p、miR-375联合预测RVO并发ME患者的ROC曲线下面积（AUC）为0.983（95%CI：0.936~0.998），优于各自单独预测（Z分别为2.854、3.133、4.297，均P<0.01）。结论 RVO并发ME患者的血清miR-155-5p、miR-17-5p、miR-375水平与黄斑水肿程度密切相关，三者联合对患者预后有较高的预测效能。

关键词: 视网膜静脉闭塞, 微RNAs, 黄斑水肿, 预后, miR-155-5p, miR-17-5p, miR-375

Abstract:

Objective To discuss the correlation between serum miR-155-5p, miR-17-5p, miR-375 and the degree of macular edema (ME) in patients with retinal vein occlusion (RVO). Methods A total of 103 patients with RVO combined with ME admitted to our hospital from January 2020 to November 2024 were selected as the observation group. According to the severity of ME, patients with RVO combined with ME were divided into 47 cases of mild, 34 cases of moderate and 22 cases of severe. Based on the prognosis, patients were classified into the poor prognosis group (38 cases) and the good prognosis group (65 cases). Another 103 patients with simple RVO in our hospital during the same period were selected as the control group. The levels of serum miR-155-5p, miR-17-5p and miR-375 were detected in the control group and the observation group. The correlation of serum miR-155-5p, miR-17-5p, miR-375 and the degree of ME were analyzed by Spearman correlation analysis method. Logistic analysis was performed to identify the influencing factors of prognosis in patients with RVO complicated with ME. Receiver operating characteristic (ROC) analysis was used to evaluate the predictive value of serum miR-155-5p, miR-17-5p and miR-375 for the prognosis of patients with RVO complicated with ME. Results Compared with the control group, serum miR-155-5p and miR-17-5p were higher in the observation group, and miR-375 level was lower (P<0.05). As the degree of ME increased, the serum miR-155-5p and miR-17-5p increased sequentially, while the miR-375 decreased sequentially (P<0.05). The degree of ME in patients with RVO and concurrent ME was positively correlated with serum miR-155-5p and miR-17-5p (r_s=0.536, 0.524, P<0.05), and negatively correlated with serum miR-375 (r_s=-0.488, P<0.05). Compared with the good group, serum miR-155-5p and miR-17-5p were higher in the poor group, and miR-375 level was lower (P<0.05). The increased miR-155-5p and miR-17-5p levels, and the decreased miR-375 were risk factors affecting the poor prognosis of patients with RVO complicated with ME (P<0.05). The AUC of the union of serum miR-155-5p, miR-17-5p and miR-375 in predicting the prognosis of patients with RVO and concurrent ME was 0.983, which was better than the individual prediction of miR-155-5p, miR-17-5p and miR-375 (Z _{union - miR-155-5p}=2.854, P=0.004, Z _{union - miR-17-5p}=3.133, P=0.002, Z _{union - miR-375}=4.297, P<0.001). Conclusion The serum miR-155-5p, miR-17-5p and miR-375 levels in patients with RVO complicated with ME are closely related to the degree of macular edema, and the combination of the three has a high predictive efficacy for the prognosis of patients.

Key words: retinal vein occlusion, microRNAs, macular edema, prognosis, miR-155-5p, miR-17-5p, miR-375

中图分类号:

R774

图/表 9

参考文献 24

[1]	Cai X, Zhao J, Dang Y. Combination therapy with anti-VEGF and intravitreal dexamethasone implant for macular edema secondary to retinal vein occlusion[J]. Curr Eye Res, 2024, 49(8):872-878. doi:10.1080/02713683.2024.2343055.
[2]	Cornish E E, Zagora S L, Spooner K, et al. Management of macular oedema due to retinal vein occlusion:an evidence-based systematic review and meta-analysis[J]. Clin Exp Ophthalmol, 2023, 51(4):313-338. doi:10.1111/ceo.14225.
[3]	Haydinger C D, Ferreira L B, Williams K A, et al. Mechanisms of macular edema[J]. Front Med (Lausanne), 2023, 10:1128811. doi:10.3389/fmed.2023.1128811.
[4]	Zhang Q, Qi S, You J, et al. The role of retinal glial cells and related factors in macular edema[J]. Biochem Biophys Res Commun, 2024, 695:149415. doi:10.1016/j.bbrc.2023.149415.
[5]	Patil N S, Mihalache A, Dhoot A S, et al. The impact of residual retinal fluid following intravitreal anti-vascular endothelial growth factor therapy for diabetic macular edema and macular edema secondary to retinal vein occlusion:a systematic review[J]. Ophthalmic Surg Lasers Imaging Retina, 2023, 54(1):50-58. doi:10.3928/23258160-20221122-01.
[6]	陶丹, 刘莉, 杨家义. 微小RNA表达在1型糖尿病视网膜病变中的研究进展[J]. 中国实用医药, 2022, 17(5):209-212.
	Tao D, Liu L, Yang J Y. Research progress on microRNA expression in type 1 diabetic retinopathy[J]. China Practical Medicine, 2022, 17(5):209-212. doi:10.14163/j.cnki.11-5547/r.2022.05.076.
[7]	娄瑞特, 李兵. miR-155-5p在糖尿病视网膜病变中的作用机制和意义[J]. 眼科新进展, 2025, 45(8):603-608.
	Lou R T, Li B. The mechanism and significance of miR-155-5p in diabetic retinopathy[J]. Progress in Ophthalmology, 2025, 45(8):603-608. doi:10.13389/j.cnki.rao.2025.0104.
[8]	范敏娜, 李明. LncRNA MEG3靶向调节miR-17-5p对缺氧缺血性脑损伤新生小鼠血-脑屏障的影响[J]. 临床神经病学杂志, 2024, 37(1):56-60.
	Fan M N, Li M. The effect of LncRNA MEG3 on the blood-brain barrier of neonatal mice with hypoxic-ischemic brain injury by targeting and regulating miR-17-5p[J]. Journal of Clinical Neurology, 2024, 37(1):56-60. doi:10.3969/j.issn.1004-1648.2024.01.017.
[9]	Gluth L, Ochsenfarth C, Pham P, et al. Influence of the anesthetic technique on circulating extracellular vesicles in bladder cancer patients undergoing radical cystectomy:a prospective,randomized trial[J]. Cells, 2023, 12(20):2503-2511. doi:10.3390/cells12202503.
[10]	桂玉敏, 彭建军, 郭敬. miR-375靶向Pax6基因调控视网膜母细胞瘤Y79细胞增殖凋亡的分子机制[J]. 河北医药, 2020, 42(8):1156-1159.
	Gui Y M, Peng J J, Guo J. Molecular mechanism of miR-375 targeting Pax6 gene regulating the proliferation and apoptosis of retinoblastoma-Y79 cells[J]. Hebei Medical Journal, 2020, 42(8):1156-1159. doi:10.3969/j.issn.1002-7386.2020.08.008.
[11]	李凤鸣, 谢立信. 中华眼科学[M]. 3版. 北京: 人民卫生出版社, 2014:21-32.
	Li F M, Xie L X. Chinese Ophthalmology[M]. 3rd Ed. Beijing: People's Medical Publishing House, 2014:21-32.
[12]	王佳艳, 王凯, 姜燕荣. 糖尿病视网膜病变和相关黄斑水肿的国际临床分类[J]. 中国糖尿病杂志, 2009, 17(10):791-792.
	Wang J Y, Wang K, Jiang Y R. International clinical classification of diabetic retinopathy and associated macular edema[J]. Chinese Journal of Diabetes, 2009, 17(10):791-792.
[13]	Sivaprasad S, Amoaku W M, Hykin P, et al. The royal college of ophthalmologists guidelines on retinal vein occlusions:executive summary[J]. Eye(Lond), 2016, 30(4):642. doi:10.1038/eye.2016.16.
[14]	Yin S, Cui Y, Jiao W, et al. Potential prognostic indicators for patients with retinal vein occlusion[J]. Front Med (Lausanne), 2022, 9:839082. doi:10.3389/fmed.2022.839082.
[15]	Shi Y, Li Z, Li K, et al. miR-155-5p accelerates cerebral ischemia-reperfusion inflammation injury and cell pyroptosis via DUSP14/ TXNIP/NLRP3 pathway[J]. Acta Biochim Pol, 2022, 69(4):787-793. doi:10.18388/abp.2020_6095.
[16]	Xu H, Li X, Liu K, et al. PM2.5 promotes macrophage-mediated inflammatory response through airway epithelial cell-derived exosomal miR-155-5p[J]. J Inflamm Res, 2024, 17:8555-8567. doi:10.2147/JIR.S482509.
[17]	林淑玫, 吴京, 马明, 等. miR-155-5p/SOCS1在大鼠角膜移植排斥反应中的作用[J]. 眼科新进展, 2021, 41(2):140-144.
	Lin S M, Wu J, Ma M, et al. Role of miR-155-5p/SOCS1 in corneal graft rejection in rats[J]. Progress in Ophthalmology, 2021, 41(2):140-144.
[18]	Chen X, Wang X, Cui Z, et al. M1 Microglia-derived exosomes promote activation of resting microglia and amplifies proangiogenic effects through Irf1/miR-155-5p/Socs1 axis in the retina[J]. Int J Biol Sci, 2023, 19(6):1791-1812. doi:10.7150/ijbs.79784.
[19]	Cho H, Hwang M, Hong E H, et al. Micro-RNAs in the aqueous humour of patients with diabetic macular oedema[J]. Clin Exp Ophthalmol, 2020, 48(5):624-635. doi:10.1111/ceo.13750.
[20]	王秋莲, 吴著明, 叶鹏飞. circZNF652靶向调控miR-17-5p对糖氧剥夺诱导的人脑血管内皮细胞损伤的影响[J]. 中国老年学杂志, 2023, 43(21):5341-5345.
	Wang Q L, Wu Z M, Ye P F. The effect of circZNF652 targeting regulation of miR-17-5p on the injury of human cerebral vascular endothelial cells induced by glucose-oxygen deprivation[J]. Chinese Journal of Geriatrics, 2023, 43(21):5341-5345. doi:10.3969/j.issn.1005-9202.2023.21.061.
[21]	Zhao K, Jiang Y, Zhang J, et al. Celastrol inhibits pathologic neovascularization in oxygen-induced retinopathy by targeting the miR-17-5p/HIF-1α/VEGF pathway[J]. Cell Cycle, 2022, 21(19):2091-2108. doi:10.1080/15384101.2022.2087277.
[22]	Bai X, Liu X, Wu H, et al. CircFUNDC1 knockdown alleviates oxygen-glucose deprivation-induced human brain microvascular endothelial cell injuries by inhibiting PTEN via miR-375[J]. Neurosci Lett, 2022, 770:136381. doi:10.1016/j.neulet.2021.136381.
[23]	Gong R, Han R, Zhuang X, et al. MiR-375 mitigates retinal angiogenesis by depressing the JAK2/STAT3 pathway[J]. Aging (Albany NY), 2022, 14(16):6594-6604. doi:10.18632/aging.204232.
[24]	张悦之, 殷小龙, 邓燕, 等. miR-375靶向PI3K/AKT通路在高糖诱导的人视网膜内皮细胞增殖和血管生成中的作用[J]. 眼科新进展, 2024, 44(2):89-93.
	Zhang Y Z, Yin X L, Deng Y, et al. Effect of micro ribonucleic acid-375 targeting phosphatidylinositol 3-kinase/protein kinase B pathway on high glucose-induced proliferation and angiogenesis of human retinal endothelial cells[J]. Progress in Ophthalmology, 2024, 44(2):89-93. doi:10.13389/j.cnki.rao.2024.0018.

组别	miR-155-5p	miR-17-5p	miR-375
对照组	1.02±0.21	1.01±0.17	1.01±0.19
观察组	1.47±0.41	1.44±0.44	0.78±0.23
t	9.926^＊＊	9.198^＊＊	7.919^＊＊

组别	miR-155-5p	miR-17-5p	miR-375
对照组	1.02±0.21	1.01±0.17	1.01±0.19
观察组	1.47±0.41	1.44±0.44	0.78±0.23
t	9.926^＊＊	9.198^＊＊	7.919^＊＊

组别	n	miR-155-5p	miR-17-5p	miR-375
轻度组	47	1.19±0.27	1.17±0.31	0.91±0.21
中度组	34	1.58±0.31^a	1.55±0.34^a	0.74±0.20^a
重度组	22	1.91±0.34^ab	1.87±0.36^ab	0.55±0.18^ab
F		46.663^＊＊	36.064^＊＊	24.964^＊＊

组别	n	miR-155-5p	miR-17-5p	miR-375
轻度组	47	1.19±0.27	1.17±0.31	0.91±0.21
中度组	34	1.58±0.31^a	1.55±0.34^a	0.74±0.20^a
重度组	22	1.91±0.34^ab	1.87±0.36^ab	0.55±0.18^ab
F		46.663^＊＊	36.064^＊＊	24.964^＊＊

组别	n			年龄/岁			男性	BMI/（kg/m²）			眼压/mmHg
良好组	65			53.45±6.27			35（53.85）	23.58±2.43			15.83±1.89
不良组	38			53.86±6.36			20（52.63）	23.62±2.36			16.52±2.18
t或χ²				0.328			0.014	0.061			1.702
组别		收缩压/mmHg				舒张压/mmHg			糖尿病史			吸烟史
良好组		129.45±14.71				92.54±9.74			18（27.69）			32（49.23）
不良组		134.47±15.19				96.16±10.36			12（31.58）			20（52.63）
t或χ²		1.653				1.778			0.175			0.111
组别			饮酒史		空腹血糖/（mmol/L）			总胆固醇/（mmol/L）		三酰甘油/（mmol/L）
良好组			24（36.92）		6.92±1.67			5.34±1.17		1.89±0.43
不良组			16（42.11）		7.58±2.25			5.81±1.46		1.98±0.54
t或χ²			0.271		1.569			1.792		0.934