增生性糖尿病视网膜病变患者房水及玻璃体中IL-8、CXCR1、CXCR2表达及意义
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摘要
目的探讨增生性糖尿病视网膜病变(PDR)房水及玻璃体中白细胞介素-8(IL-8)、CXCR1、CXCR2蛋白表达及意义。方法选择本院糖尿病视网膜病变(DR)并行白内障手术及玻璃体切除术的患者94例为病例组,分为非PDR组(非增生组) 50例,PDR组(增生组) 44例,同期选择本院门诊正常体检者68例为对照组。测定糖化血红蛋白(Hb A1c)、空腹血糖(FPG)、超敏C反应蛋白(hs-CRP)以及房水(房)、玻璃体(玻)中的IL-8、CXCR1、CXCR2水平。结果病例组IL-8 (房)、IL-8 (玻)、CXCR1 (房)、CXCR1 (玻)、CXCR2 (房)、CXCR2 (玻)、Hb A1c、hs-CRP、FPG水平高于对照组,差异有统计学意义(P <0. 05);增生组IL-8 (房)、IL-8 (玻)、CXCR1 (房)、CXCR1(玻)、CXCR2(房)、CXCR2(玻)、Hb A1c、hs-CRP、FPG水平高于非增生组,差异有统计学意义(P <0. 05);IL-8(房)、CXCR1(玻)、CXCR2(玻)三者的ROC曲线下面积(AUC)相近,皆小于Hb A1c,IL-8 (房)、CXCR1 (玻)、CXCR2(玻)诊断PDR的灵敏度、特异度相近(P> 0. 05),皆小于Hb A1c(P <0. 05)。结论 PDR患者房水及玻璃体中的高水平IL-8、CXCR1、CXCR2可能与PDR病变的进展密切相关; IL-8(房)、CXCR1(玻)、CXCR2(玻)诊断PDR具有较高的灵敏度、特异度,值得在临床上推广应用;高水平的IL-8(房)、CXCR1(玻)、CXCR2(玻)、Hb A1c均为DR为增生性的危险因素。
Objective To investigate the expression and significance of IL-8,CXCR1 and CXCR2 in the aqueous humor and vitreous body of patients with proliferative diabetic retinopathy( PDR). Methods 94 cases of PDR patients who underwent cataract surgery combined with vitrectomy( case group) and 68 cases of healthy subjects( control group) who attended routine physical examination in our hospital were enrolled. The case group was further divided into two groups according to the presence of proliferation,namely,the non-proliferative group( n = 50) and the proliferative group( n =44). The levels of Hb A1 c and fast plasma glucose( FPG),as well as the levels of IL-8,CXCR1,and CXCR2 in the aqueous humor( AH) and vitreous body( VB) were measured. Results The levels of IL-8( AH),IL-8( VB),CXCR1( AH),CXCR1( VB),CXCR2( AH),CXCR2( VB),Hb A1 c,hs-CRP,and FPG were higher in the case group than in the control group( P < 0. 05); The levels of IL-8( AH),IL-8( VB),CXCR1( AH),CXCR1( VB),CXCR2( AH),CXCR2( VB),Hb A1 c,hs-CRP,and FPG were higher in the proliferative group than in the non-proliferative group( P <0. 05); High levels of IL-8( AH),CXCR1( VB),CXCR2( VB),and Hb A1 c were risk factors for hypertrophic retinopathy( P < 0. 05). The AUC,sensitivity and specificity of IL-8( AH),CXCR1( VB) and CXCR2( VB) were similar( P> 0. 05),which were all lower than those of the Hb A1 c( P < 0. 05). Conclusions High levels of IL-8,CXCR1 and CXCR2 in the AH and VB were closely related to the PDR progression. Levels of IL-8( AH),CXCR1( VB) and CXCR2( VB) have a high sensitivity and specificity in the diagnosis of PDR,and worth recommendation in the clinical practice.High levels of IL-8( AH),CXCR1( VB),CXCR2( VB) and Hb A1 c are all risk factors for PDR.
Objective To investigate the expression and significance of IL-8,CXCR1 and CXCR2 in the aqueous humor and vitreous body of patients with proliferative diabetic retinopathy( PDR). Methods 94 cases of PDR patients who underwent cataract surgery combined with vitrectomy( case group) and 68 cases of healthy subjects( control group) who attended routine physical examination in our hospital were enrolled. The case group was further divided into two groups according to the presence of proliferation,namely,the non-proliferative group( n = 50) and the proliferative group( n =44). The levels of Hb A1 c and fast plasma glucose( FPG),as well as the levels of IL-8,CXCR1,and CXCR2 in the aqueous humor( AH) and vitreous body( VB) were measured. Results The levels of IL-8( AH),IL-8( VB),CXCR1( AH),CXCR1( VB),CXCR2( AH),CXCR2( VB),Hb A1 c,hs-CRP,and FPG were higher in the case group than in the control group( P < 0. 05); The levels of IL-8( AH),IL-8( VB),CXCR1( AH),CXCR1( VB),CXCR2( AH),CXCR2( VB),Hb A1 c,hs-CRP,and FPG were higher in the proliferative group than in the non-proliferative group( P <0. 05); High levels of IL-8( AH),CXCR1( VB),CXCR2( VB),and Hb A1 c were risk factors for hypertrophic retinopathy( P < 0. 05). The AUC,sensitivity and specificity of IL-8( AH),CXCR1( VB) and CXCR2( VB) were similar( P> 0. 05),which were all lower than those of the Hb A1 c( P < 0. 05). Conclusions High levels of IL-8,CXCR1 and CXCR2 in the AH and VB were closely related to the PDR progression. Levels of IL-8( AH),CXCR1( VB) and CXCR2( VB) have a high sensitivity and specificity in the diagnosis of PDR,and worth recommendation in the clinical practice.High levels of IL-8( AH),CXCR1( VB),CXCR2( VB) and Hb A1 c are all risk factors for PDR.
引文
[1]陈淑惠,孟倩丽,张敏,等. 2型糖尿病视网膜病变与糖尿病其他并发症的相关性[J].国际眼科杂志,2016,16(2):309-312.
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[10] Dong L,Bai J,Jiang X,et al. The gene polymorphisms of IL-8(-251T/A)and IP-10(-1596C/T)are associated with susceptibility and progression of type 2 diabetic retinopathy in northern Chinese population[J]. Eye(Lond),2017,31(4):601-607.
[11] Chan LP,Wang LF,Chiang FY,et al. IL-8 promotes HNSCC progression on CXCR1/2-meidated NOD1/RIP2 signaling pathway[J]. Oncotarget,2016,7(38):61820-61831.
[12]刘家琦,李凤鸣.实用眼科学[M].北京:人民卫生出版社,2006:480-483
[13] Yang X,Xu J,Wang R,et al. A randomized controlled trial of conbercept pretreatment before vitrectomy in proliferative diabetic retinopathy[J]. J Ophthalmol,2016,2016:2473234.
[14] Mukhtar A,Khan MS,Junejo M,et al. Effect of pan retinal photocoagulation on central macular thickness and visual acuity in proliferative diabetic retinopathy[J]. Pak J Med Sci,2016,32(1):221-224.
[15] Arjamaa O,Pllnen M. Increased IL-6 levels in the vitreous of proliferative diabetic retinopathy(PDR)[J]. Acta Ophthalmologica,2011,89(246):5-7
[16] Da SPB,Polina ER,Crispim D,et al. Interleukin-10-1082A> G(rs1800896)polymorphism is associated with diabetic retinopathy in type 2 diabetes[J]. Diabetes Res Clin Pract,2018,138:187-192.
[17] Houssen ME,MAB E,El-Kannishy A,et al. Serum and aqueous humor concentrations of interleukin-27 in diabetic retinopathy patients[J]. Int Ophthalmol,2018,38(5):1817-1823.
[18] Mugisho OO,Rupenthal ID,Squirrell DM,et al. Intravitreal proinflammatory cytokines in non-obese diabetic mice:Modelling signs of diabetic retinopathy[J]. PLo S One,2018,13(8):e0202156.
[19] Lamine LB,Turki A,Al-Khateeb G,et al. Elevation in cfirculating soluble CD40 ligand concentrations in type 2 diabetic retinopathy and association with its severity[J]. Exp Clin Endocrinol Diabetes,2018.
[20] Kawasaki R,Kitano S,Sato Y,et al. Factors associated with nonproliferative diabetic retinopathy in patients with type 1 and type2 diabetes:the Japan diabetes complication and its prevention prospective study(JDCP study 4)[J]. Diabetol Int,2019,10(1):3-11.
[2] Arevalo JF,TYA L. Intravitreal bevacizumab in diabetic retinopathy. Recommendations from the Pan-American Collaborative Retina Study Group(PACORES):The 2016 Knobloch Lecture[J]. Asia Pac J Ophthalmol(Phila),2018,7(1):36-39.
[3] Voets M,Mollersen K,Bongo LA. Replication study:Development and validation of deep learning algorithm for detection of diabetic retinopathy in retinal fundus photographs[J],2018,4(2):90-91.
[4] Thomas AA,Feng B,Chakrabarti S. ANRIL:A regulator of VEGF in diabetic retinopathy[J]. Invest Ophthalmol Vis Sci,2017,58(1):470-480.
[5] Parikh RN,Traband A,Kolomeyer AM,et al. Intravitreal bevacizumab for the treatment of vitreous jemorrhage due to proliferative diabetic retinopathy[J]. Am J Ophthalmol,2017,176:194-202.
[6] Loukovaara S,Piippo N,Kinnunen K,et al. NLRP3 inflammasome activation is associated with proliferative diabetic retinopathy[J].Acta Ophthalmol,2017,95(8):803-808.
[7] Gonzalez-Salinas R,Garcia-Gutierrez MC,Garcia-Aguirre G,et al.Evaluation of VEGF gene polymorphisms and proliferative diabetic retinopathy in Mexican population[J]. Int J Ophthalmol,2017,10(1):135-139.
[8] S Feng,H Yu,Y Yu,et al. Levels of inflammatory cytokines IL-1β,IL-6,IL-8,IL-17A,and TNF-αin aqueous humour of patients with diabetic retinopathy[J]. J Diabetes Res,2018,2018(1):1-6.
[9] Cicik E,Tekin H,Akar S,et al. Interleukin-8,nitric oxide and glutathione status in proliferative vitreoretinopathy and proliferative diabetic retinopathy[J]. Ophthalmic Res,2003,35(5):251-255.
[10] Dong L,Bai J,Jiang X,et al. The gene polymorphisms of IL-8(-251T/A)and IP-10(-1596C/T)are associated with susceptibility and progression of type 2 diabetic retinopathy in northern Chinese population[J]. Eye(Lond),2017,31(4):601-607.
[11] Chan LP,Wang LF,Chiang FY,et al. IL-8 promotes HNSCC progression on CXCR1/2-meidated NOD1/RIP2 signaling pathway[J]. Oncotarget,2016,7(38):61820-61831.
[12]刘家琦,李凤鸣.实用眼科学[M].北京:人民卫生出版社,2006:480-483
[13] Yang X,Xu J,Wang R,et al. A randomized controlled trial of conbercept pretreatment before vitrectomy in proliferative diabetic retinopathy[J]. J Ophthalmol,2016,2016:2473234.
[14] Mukhtar A,Khan MS,Junejo M,et al. Effect of pan retinal photocoagulation on central macular thickness and visual acuity in proliferative diabetic retinopathy[J]. Pak J Med Sci,2016,32(1):221-224.
[15] Arjamaa O,Pllnen M. Increased IL-6 levels in the vitreous of proliferative diabetic retinopathy(PDR)[J]. Acta Ophthalmologica,2011,89(246):5-7
[16] Da SPB,Polina ER,Crispim D,et al. Interleukin-10-1082A> G(rs1800896)polymorphism is associated with diabetic retinopathy in type 2 diabetes[J]. Diabetes Res Clin Pract,2018,138:187-192.
[17] Houssen ME,MAB E,El-Kannishy A,et al. Serum and aqueous humor concentrations of interleukin-27 in diabetic retinopathy patients[J]. Int Ophthalmol,2018,38(5):1817-1823.
[18] Mugisho OO,Rupenthal ID,Squirrell DM,et al. Intravitreal proinflammatory cytokines in non-obese diabetic mice:Modelling signs of diabetic retinopathy[J]. PLo S One,2018,13(8):e0202156.
[19] Lamine LB,Turki A,Al-Khateeb G,et al. Elevation in cfirculating soluble CD40 ligand concentrations in type 2 diabetic retinopathy and association with its severity[J]. Exp Clin Endocrinol Diabetes,2018.
[20] Kawasaki R,Kitano S,Sato Y,et al. Factors associated with nonproliferative diabetic retinopathy in patients with type 1 and type2 diabetes:the Japan diabetes complication and its prevention prospective study(JDCP study 4)[J]. Diabetol Int,2019,10(1):3-11.