[1]刘有娅,李红军.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[J].眼科新进展,2020,40(11):1055-1059.[doi:10.13389/j.cnki.rao.2020.0236]
　LIU Youya,LI Hongjun.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[J].Recent Advances in Ophthalmology,2020,40(11):1055-1059.[doi:10.13389/j.cnki.rao.2020.0236]
点击复制

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/HTML
分享到：

《眼科新进展》[ISSN:1003-5141/CN:41-1105/R]

卷:
40卷
期数:
2020年11期
页码:
1055-1059
栏目:
应用研究
出版日期:
2020-11-05

文章信息/Info

Title:
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
作者:
刘有娅; 李红军
405400　重庆市，重庆市开州区人民医院眼科
Author(s):
LIU Youya; LI Hongjun
Department of Ophthalmology,Kaizhou District People’s Hospital of Chongqing,Chongqing 405400，China
关键词:
miRNA-15b; 成纤维细胞生长因子2; 增生型糖尿病视网膜病变; 玻璃体; 视网膜增生膜组织
Keywords:
microRNA-15b;  fibroblast growth factor 2;  proliferative diabetic retinopathy;  vitreous humor;  retinal proliferative membrane tissues
分类号:
R774
DOI:
10.13389/j.cnki.rao.2020.0236
文献标志码:
A
摘要:
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。
Abstract:
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.

参考文献/References:

［1］　庞敏,魏祎,翁孝刚.2型糖尿病视网膜病变危险因素分析［J］.新乡医学院学报,2020,37(3):270-273.
PANG M,WEI Y,WONG X G.Analysis of risk factors of type 2 diabetic retinopathy［J］.J Xinxiang Med Univ,2020,37(3):270-273.
［2］　郭庆敏,孟旭霞,刘鹏辉,周贤慧.Notch受体蛋白1、Delta样配体4在增生型糖尿病视网膜病变新生血管形成中的作用［J］.中华眼底病杂志,2017,33(3):275-280.
GUO Q M,MENG X X,LIU P H,ZHOU X H.The effect of Notch1 and Delta-like ligand 4 in the neovascularization of the proliferative diabetic retinopathy［J］.Chin J Ocul Fundus Dis,2017,33(3):275-280.
［3］　曾少杰,谢怀林,何小娟.增生型糖尿病视网膜病变与VEGF和CTGF水平的相关性及治疗启示［J］.临床眼科杂志,2018,26(4):296-300.
ZENG S J,XIE H L,HE X J.The relationship between the levels of VEGF and CTGF in proliferative diabetic retinopathy and its therapeutic implications［J］.J Clin Ophthalmol,2018,26(4):296-300.
［4］　彭芬,李翠洁,吴素英,周晓光.三七总皂苷通过长链非编码RNA对氧诱导视网膜病变小鼠新生血管的抑制作用［J］.武汉大学学报(医学版),2019,40(4):529-533.
PENG F,LI C J,WU S Y,ZHOU X G.Panax notoginseng saponins inhibits neovascularization of oxygen-induced neonatal retinopathy mouse by lncRNAs［J］.Med J Wuhan Univ,2019,40(4):529-533.
［5］　GURUNG H R,CARR M M,BRYANT K,CHUCAIR-ELLIOTT A J,CARR D J.Fibroblast growth factor-2 drives and maintains progressive corneal neovascularization following HSV-1 infection［J］.Mucosal Immunol,2018,11(1):172-185.
［6］　LU L,LI Y M,WEN H,FENG C C.Overexpression of miR-15b promotes resistance to sunitinib in renal cell carcinoma［J］.J Cancer,2019,10(15):3389-3396.
［7］　MARATHE P H,GAO X H,CLOSE K L.American diabetes association standards of medical care in diabetes-2017［J］.J Diabetes Care,2017,9(4):320.
［8］　SOARES M,NEVES C,MARQUES I P,PIRES I,SCHWARTZ C,COSTA M A,et al.Comparison of diabetic retinopathy classification using fluorescein angiography and optical coherence tomography angiography［J］.Br J Ophthalmol,2017,101(1):62-68.
［9］　丁秋爱,董乐,游志鹏.增生型糖尿病视网膜病变患者血清及玻璃体中IL-19和VEGF表达水平的研究［J］.免疫学杂志,2018,34(5):443-448.
DING Q A,DONG L,YOU Z P.The expression of IL-19 and VEGF in serum and vitreous of patients with proliferative diabetic retinopathy［J］.Immunol J,2018,34(5):443-448.
［10］　ZHAO X Y,XIA S,CHEN Y X.Antivascular endothelial growth factor agents pretreatment before vitrectomy for complicated proliferative diabetic retinopathy:a meta-analysis of randomised controlled trials［J］.Br J Ophthalmol,2018,102(8):1077-1085.
［11］　JAMPOL L M,ODIA I,GLASSMAN A R,BARKER C W,BHORADE A M,HAN D P,et al.Panretinal photocoagulation versus ranibizumab for proliferative diabetic retinopathy:Comparison of peripapillary retinal nerve fiber layer thickness in a randomized clinical trial［J］.Retina,2019,39(1):69-78.
［12］　LIU E,ESTEVEZ J,KAIDONIS G,MARK H,LANDERS J,LAKE S,et al.Long-term survival rates of patients undergoing vitrectomy for diabetic retinopathy in an Australian population:A population-based audit response［J］.Clin Exp Ophthalmol,2019,47(6):817-818.
［13］　文晓霞,谭德文,李红军,刘有娅,蒋小均,方腾.康柏西普辅助治疗增生型糖尿病视网膜病变患者术前用药时机分析及对新生血管膜VEGF的影响［J］.中国医师杂志,2019,21(1):89-93.
WEN X X,TAN D W,LI H J,LIU Y Y,JIANG X J,FANG T.Preoperative medication timing analysis and effect on neovascular membrane vascular endothelial growth factor in patients with proliferative diabetic retinopathy assisted by Conbercept［J］.J Chin Physician,2019,21(1):89-93.
［14］　MOON S W,SUN Y Y,WARTHER D,HUFFMAN K,FREEMAN W R,SAILOR M J,et al.New model of proliferative vitreoretinopathy in rabbit for drug delivery and pharmacodynamic studies［J］.Drug Deliv,2018,25(1):600-610.
［15］　MASAKI K,SAKAI M,KUROKI S,JO J I,HOSHINA K,FUJIMORI Y.FGF2 has distinct molecular functions from GDNF in the mouse germline niche［J］.Stem Cell Reports,2018,10(6):1782-1792.
［16］　MCKENZIE J,SMITH C,KARUPPAIAH K,LANGBERG J,SHLVA M J,ORNITZ D M.Osteocyte death and bone overgrowth in mice lacking fibroblast growth factor receptors 1 and 2 in mature osteoblasts and osteocytes［J］.J Bone Miner Res,2019,34(9):1660-1675.
［17］　RENAUD-GABARDOS E,TATIN F,HANTELYS F,LEBAS B,CALISE D,KUNDUZOVA O,et al.Therapeutic benefit and gene network regulation by combined gene transfer of Apelin,FGF2,and SERCA2a into ischemic heart［J］.Mol Ther,2018,26(3):902-916.
［18］　YANG Q H,ZHANG Y,JIANG J,WU M M,HAN Q,BO Q Y,et al.Protective effects of a novel drug RC28-E blocking both VEGF and FGF2 on early diabetic rat retina［J］.Int J Ophthalmol,2018,11(6):935-944.
［19］　KIM S,KANG H.miR-15b induced by platelet-derived growth factor signaling is required for vascular smooth muscle cell proliferation［J］.BMB Rep,2013,46(11):550-554.

备注/Memo

备注/Memo:
重庆市卫生计生委科研基金项目（编号：2017MSXM186）
更新日期/Last Update: 2020-11-05