小剂量多次注射链脲佐菌素建立糖尿病早期视网膜病变动物模型

目的多次小剂量注射链脲佐菌素(STZ)制作糖尿病(DM)早期大鼠视网膜病变(DR)动物模型。方法雄性SD大鼠75只,体重(180±15)g。随机分为对照组(CON组,n=30)和模型组(DM组,n=45)。DM组按30mg/kg体重腹腔注射3%的STZ,连续5 d。成模后每周测量体重、血糖等指标。分别在成模后第4、8、12周各组随机安乐死10只动物,对视网膜组织进行H.E染色、免疫组化、消化铺片及透射电镜超微结构观察。结果模型成立后第2周,动物表现出多食、多饮、多尿的糖尿病症状。与对照组比较,模型大鼠4周时仅见视网膜变薄,8周时视网膜内皮细胞增生,毛细血管基底膜增厚,内皮细胞指状突起,吞饮泡增多。12周时毛细血管膨大,毛细血管细胞凋亡,核固缩、深染。视网膜变薄,神经节细胞数量减少。视网膜周细胞线粒体肿胀,嵴脱落空泡样变。模型组大鼠视网膜GFAP阳性细胞主要分布在节细胞层和神经纤维层,呈条索状连续排列,阳性细胞数明显减少。结论小剂量多次注射STZ诱导的大鼠DR模型表现出人类早期视网膜病变相似的特征,可用于发病机理、药效学等方面的研究。     

STZ诱发实验恒河猴糖尿病性视网膜并发症模型的建立

目的　建立糖尿病性视网膜并发症 (DiabeticRetinopathy ,DR)动物模型。方法　本研究选用 4只健康成熟的雄性恒河猴分别以剂量为 6 0mg kg、4 5mg kg静脉一次注射及 30mg kg静脉二次注射 (中间间隔 15d)链脲佐菌素 (Streptozotocin ,STZ)。结果　使用不同剂量的STZ注射恒河猴 ,分别造成了胰岛素依赖性糖尿病 (InsulinDepen dentDiabetesMellitus ,IDDM)及慢性持续性高血糖症 (StateofChronicHyperglycemia,SCH)两种类型的模型 ,从而诱导出不同程度的DR。眼底荧光造影结果显示∶用药后 6 3～ 91d4只实验猴均出现不同程度的视网膜病 ,分别显示早期眼底微血管动脉扩张 ,视网膜出血瘤 ,微血管瘤及新生血管、晚期白内障等。结论　本研究所建立的糖尿病性视网膜并发症模型 ,对于进一步研究糖尿病及其并发症的发病机理 ,筛选及开发治疗糖尿病性视网膜病的新药及药物安全性评价将会具有广阔的应用前景     

2型糖尿病患者血糖波动与糖尿病视网膜病变的相关性分析

目的:探讨2型糖尿病(T2DM)患者血糖波动与糖尿病视网膜病变(DR)的关系.方法:T2DM患者进行眼底照相或眼底荧光造影,根据DR程度分为糖尿病背景期视网膜病变(BDR)组、糖尿病增殖期视网膜病变(PDR)组、无视网膜病变(NDR)组,记录年龄、性别、体重指数、病程、测量血压、糖化血红蛋白、空腹胰岛素、餐后2h胰岛素、空腹C-肽、餐后2hC-肽、血脂指标.选取三组中上述基线指标具有可比性的病例共106例(BDR组38例,PDR组35例,NDR组33例)纳入观察.采用动态血糖监测系统(CGMS)连续监测患者血糖72 h.结果:各组间平均血糖水平(MBG)、血糖标准差(SDBG)、平均血糖波动幅度(MAGE)及血糖波动最大幅度(LAGE)相比较有统计学差异(P＜0.05).Spearman相关分析显示,糖尿病视网膜病变(DR)与MBG、SDBG、MAGE及LAGE呈正相关(P＜0.05).校正MBG后,糖尿病视网膜病变(DR)与SDBG、MAGE及LAGE的相关系数分别为0.297、0.396、0.284(P＜0.01).结论:血糖波动与糖尿病视网膜病变(DR)的发生发展有关,应尽早干预.     

肾上腺髓质素在糖尿病视网膜细胞高表达的研究

探讨肾上腺髓质素(Adrenomedullin,AM)在糖尿病视网膜病变(Diabeticretinopathy,DR)发病中的作用。Sprague-Dawley雄性大鼠尾静脉注射链脲佐菌素造模,以血糖测定和尿糖水平测定进行筛选,正常对照组尾静脉注射等量枸橼酸钠缓冲液。成模后继续饲养4周,取出眼球视网膜组织,连续冰冻切片,用免疫组织化学SABC法染色观察各组大鼠视网膜RPE细胞AM的表达情况。糖尿病大鼠成模前,两组动物的体重、血糖和尿糖检测结果间无显著性差异(P>0.05)。成模后4周,糖尿病组与正常组大鼠体重、血糖和尿糖数值差异有显著性意义(P<0.01)。AM在正常组大鼠视网膜节细胞层及内核层均有表达,正常组大鼠视网膜AM的光密度值为76.3±5.3,单位面积AM阳性细胞数为(4.5±1.1)×103/mm2。糖尿病大鼠视网膜内RPE细胞肾上腺髓质素表达显著增强,糖尿病大鼠视网膜RPE细胞AM的光密度值为105.7±11.9,单位面积AM阳性细胞数为(17.9±2.3)×103/mm2。两组相比,差异具有显著性(P<0.01)。AM在糖尿病大鼠视网膜RPE细胞表达量增加很可能是DR发生、发展的重要因素。     

糖尿病大鼠视网膜血管铺片技术的改进及形态学观察

近年来我国糖尿病的患病率在逐年增加 ,病例总数居世界第二。糖尿病视网膜病变 (DiabeticRetinopathy DR)是糖尿病最为常见和严重的微血管病的并发症之一 ,也是成人主要致盲的疾病之一 ,病程愈长致盲机率愈高。DR发病机理至今尚未完全阐明 ,认为与多种因素的协同作用有关。目前 ,临床尚无有效的防治手段。因此研究 DR的发病机理 ,研制出有效治疗药物的任务迫在眉睫。视网膜毛细血管铺片技术是一种研究 DR理想的方法 ,不仅可清楚地观察到毛细血管的结构、走行、分布。还可进行定量分析细胞之间的比例、血管的密度、管径的大小等。但是 ,…     

川芎嗪联合氨胍治疗对糖尿病大鼠视网膜血管内皮生长因子表达的影响

目的 观察川芎嗪联合氨胍治疗对糖尿病大鼠视网膜血管内皮生长因子（VEGF）表达的影响。探讨川芎嗪联合氨胍治疗糖尿病视网膜病变（DR）的机制。方法 应用链尿佐菌素（STZ）制作糖尿病大鼠模型。分为正常对照组,糖尿病未治疗组,川芎嗪治疗组,氨胍治疗组和川芎嗪联合氨胍治疗组,分别于第4周,第12周和第20周应用免疫组化方法观察各组大鼠视网膜组织VEGF表达的变化。结果 正常大鼠视网膜组织VEF表达仅见于内核层,糖尿病大鼠视网膜组织VEGF阳性表达随周龄的延长而增强,且在毛细血管内和节细胞层可见VEGF表达,治疗12周和20周后,川芎嗪治疗组和氨胍治疗组大鼠视网膜组织VEGF阳性表达比未治疗组明显减弱,但仍高于正常对照组,而川芎嗪联合氨胍治疗组视网膜组织VEGF表达接近正常。结论 川芎嗪联合氨胍治疗可抑制糖尿病大鼠视网膜VEGF的过度表达。是川芎嗪联合氨胍治疗糖尿病视网膜病变（DR）的机制之一。     

巨噬细胞外泌体在增殖性糖尿病视网膜病变中的研究进展

糖尿病视网膜病变(diabetic retinopathy, DR)是糖尿病患者最常见的微血管系统并发症之一，是视力丧失的主要原因。增殖性糖尿病视网膜病变(proliferative diabetic retinopathy, PDR)是DR的终末期表现，其主要的病理生理学特征是视网膜新生血管形成(retinal neovascularization, RNV)。但PDR现有治疗方式存在局限性。外泌体作为细胞间沟通交流的重要使者，其携带的非编码RNA和生物活性蛋白质等重要信号分子，通过影响血管内皮细胞的增殖和迁移，在RNV中发挥关键作用。巨噬细胞是一种多功能调节细胞，越来越多的研究表明巨噬细胞外泌体在调控新生血管形成中起重要作用。该文就巨噬细胞外泌体在增殖性糖尿病视网膜病变形成中的作用与机制研究进展进行综述。     

早期糖尿病大鼠晶状体和视网膜水通道蛋白4表达的研究

目的观察早期糖尿病大鼠晶状体、视网膜水通道蛋白4(aquaporin 4,AQP-4)表达的变化,探讨糖尿病大鼠眼组织水代谢改变的机制。方法 SD大鼠分为正常对照组和糖尿病组。制作糖尿病大鼠模型,于第4、8周取材,用免疫组化法和计算机图像分析系统半定量分析各组大鼠晶状体、视网膜AQP-4表达的变化。结果正常及糖尿病大鼠AQP-4在晶状体上皮均无表达。AQP-4在视网膜上有表达,正常大鼠主要表达于视网膜视杆视锥层、节细胞层和神经纤维层,糖尿病大鼠从内界膜延伸至视细胞层整个视网膜厚度均可见AQP-4阳性表达,特别是在神经节细胞层毛细血管内皮和神经纤维层阳性表达更明显。糖尿病大鼠视网膜组织AQP-4阳性表达标随周龄的延长而增强。结论糖尿病大鼠视网膜AQP-4的表达较正常组增强,提示水通道蛋白的表达增加是糖尿病早期发生视网膜水肿的机制之一。     

米诺环素对糖尿病大鼠视网膜神经细胞凋亡的影响

目的:观察米诺环素对糖尿病大鼠视网膜神经细胞的凋亡的影响,研究米诺环素对糖尿病视网膜神经保护作用,对米诺环素在糖尿病视网膜疾病中抑制神经细胞凋亡提供理论支持。方法:选择健康成年雄性SD大鼠30只,随机分成正常对照组、糖尿病模型组和米诺环素治疗组,每组10只。腹腔内注射链脲佐菌素(STZ)诱发大鼠糖尿病。米诺环素治疗组给予米诺环素腹腔注射(45mg/kg),共注射10d,模型组和对照组腹腔注射等体积生理盐水,于给药后8周的3组动物处死,冰浴下取其视网膜组织,随后制备视网膜石蜡切片,采用末端脱氧核糖核酸介导生物素化脱氧尿嘧啶缺口末端标记(TUNEL)法进行凋亡细胞原位标记,行视网膜神经细胞凋亡计数,对所有数据进行统计学分析。实验结果拟用均数和标准差(x±s)表示,P<0.05为差异有统计学意义。结果:相同观察时相,与阴性对照组比较,模型对照组大鼠视网膜TUNEL阳性细胞显著增多(P<0.01),在米诺环素组,大鼠视网膜TUNEL阳性细胞数比模型对照组明显减少,差异有统计学意义(P<0.01)。结论:米诺环素能有效降低糖尿病大鼠视网膜神经细胞的凋亡,对糖尿病视网膜神经细胞有保护作用。     

2型糖尿病性视网膜病变临床因素分析

目的:探讨影响2型糖尿病视网膜病变(DR)发病的相关临床因素。方法:回顾性分析483例2型糖尿病患者的临床资料。结果:2型糖尿痛DR患病率为35%(169/483),其中非增殖型视网膜病变(NPDR)73.4%(124/169),增殖型视网膜病变(PDR)26.6% (45/169)。DR患者的病程、SBP、合并肾脏病变、合并心脏病变、HbA1c、TC、TG、LDL-c、BUN和Cr均显著高于NDR患者(P<0.05);Logistic回归分析显示病程、年龄、SBP、TC、LDL-c、合并心脏病变和/或肾脏病变是DR发病的危险因素。结论:DM病程、患病年龄、SBP、HbA1c、TC、LDL-c、合并心脏病变和/或肾脏病变、肾功能是DR发生发展的危险因素。     

Diabetic Retinopathy,Classified Using the Lesion-Aware Deep Learning System,Predicts Diabetic End-Stage Renal Disease in Chinese Patients

Objective: To characterize the relationship between diabetic retinopathy (DR) and diabetic nephropathy (DN) in Chinese patients and to determine whether the severity of DR predicts end-stage renal disease (ESRD).Methods: Bilateral fundic photographs of 91 Chinese type 2 diabetic patients with biopsy-confirmed DN, not in ESRD stage, were obtained at the time of renal biopsy in this longitudinal study. The baseline severity of DR was determined using the Lesion-aware Deep Learning System (RetinalNET) in an open framework for deep learning and was graded using the Early Treatment Diabetic Retinopathy Study severity scale. Cox proportional hazard models were used to estimate the hazard ratio (HR) for the effect of the severity of diabetic retinopathy on ESRD.Results: During a median follow-up of 15 months, 25 patients progressed to ESRD. The severity of retinopathy at the time of biopsy was a prognostic factor for progression to ESRD (HR 2.18, 95% confidence interval 1.05 to 4.53, P = .04). At baseline, more severe retinopathy was associated with poor renal function, and more severe glomerular lesions. However, 30% of patients with mild retinopathy and severe glomerular lesions had higher low-density lipo-protein-cholesterol and more severe proteinuria than those with mild glomerular lesions. Additionally, 3% of patients with severe retinopathy and mild glomerular changes were more likely to have had diabetes a long time than those with severe glomerular lesions.Conclusion: Although the severity of DR predicted diabetic ESRD in patients with type 2 diabetes mellitus and DN, the severities of DR and DN were not always consistent, especially in patients with mild retinopathy or microalbuminuria.Abbreviations: CI = confidence interval; DM = diabetic mellitus; DN = diabetic nephropathy; DR = diabetic retinopathy; eGFR = estimated glomerular filtration rate; ESRD = end-stage renal disease; HbA1c = hemoglobin A1c; HR = hazard ratio; NPDR = nonproliferative diabetic retinopathy; PDR = proliferative diabetic retinopathy; SBP = systolic blood pressure; T2DM = type 2 diabetes mellitus; VEGF = vascular endothelial growth factor     

川芎嗪联合前列地尔治疗背景性糖尿病视网膜病变疗效的临床观察

目的:探讨川芎嗪(Ligustrazine)联合前列地尔(Alprostadil)治疗背景性糖尿病视网膜病变(Diabetic retinopathy,DR)的作用与疗效。方法:收集近年我院糖尿病伴背景性DR共73例(112只眼),分别按治疗中应用川芎嗪联合前列地尔或拜阿司匹林分为治疗组与对照组,比较两组治疗前后患者眼底病变改善情况。结果:川芎嗪联合前列地尔的治疗组疗效比拜阿司匹林的对照组好;眼底荧光检查表明,治疗组眼底病变改善明显好于对照组,差异显著(P<0.05)。结论:川芎嗪联合前列地尔对DR有较好的疗效。     

Diabetic retinopathy in the Eastern Morocco: Different stage frequencies and associated risk factors

Diabetes is a major cause of morbidity and mortality worldwide. It can affect many organs and, over time, leads to serious complications. Diabetic retinopathy (DR), a specific ocular complication of diabetes, remains the leading cause of vision loss and vision impairment in adults. This work is the first in Eastern Morocco aimed at identifying the different stages of DR and to determine their frequencies and associated risk factors. It is a case-control study conducted from December 2018 to July 2019 at the ophthalmology department of Al-Irfane Clinic (Oujda). Data were obtained from a specific questionnaire involving 244 diabetic patients (122 cases with retinopathy vs 122 controls without retinopathy). All results were analyzed by the EPI-Info software. This study shows a predominance of proliferative diabetic retinopathy (PDR) with 57.4% of cases (uncomplicated proliferative diabetic retinopathy (UPDR): 23.8%; complicated proliferative diabetic retinopathy (CPDR): 33.6%). The non-proliferative diabetic retinopathy (NPDR) represents 42.6% (minimal NPDR: 8.2%; moderate NPDR: 26.2%; severe NPDR: 8.2%). The determinants of DR were insulin therapy, high blood pressure, poor glycemic control and duration of diabetes. Regarding the chronological evolution, retinopathy precedes nephropathy. Diabetic nephropathy (DN) was present in 10.6% of cases especially in patients with PDR. In summary, the frequency of PDR was higher than that of NPDR. DR appears before DN with a high frequency of DN in patients with PDR. Good glycemic control and blood pressure control, as well as early diagnosis are the major preventive measures against DR.     

Influence of Uncomplicated Phacoemulsification on Central Macular Thickness in Diabetic Patients: A Meta-Analysis

ObjectiveTo evaluate the effect of uncomplicated phacoemulsification on central macular thickness (CMT) and best corrected visual acuity (BCVA) in both diabetic patients without diabetic retinopathy (DR) and diabetic patients with mild to moderate non-proliferative diabetic retinopathy (NPDR).MethodsPotential prospective observational studies were searched through PubMed and EMBASE. Standardized mean difference (SMD) and 95% confidence interval (CI) for changes in CMT and BCVA were evaluated at postoperative 1, 3 and 6 months. The pooled effect estimates were calculated in the use of a random-effects model.ResultsA total of 10 studies involving 190 eyes of diabetic patients without diabetic retinopathy and 143 eyes of diabetic patients with NPDR were identified. CMT values demonstrated a statistically significant increase after uncomplicated phacoemulsification at 1 month (SMD, -0.814; 95%CI, -1.230 to -0.399), 3 months (SMD, -0.565; 95%CI, -0.927 to -0.202) and 6 months (SMD, -0.458; 95%CI, -0.739 to -0.177) in diabetic patients with NPDR. There was no statistical difference in CMT values at postoperative 1 month (SMD, -1.206; 95%CI, -2.433 to 0.021)and no statistically significant increase in CMT values at postoperative3 months (SMD, -0.535; 95%CI, -1.252 to 0.182) and 6 months (SMD, -1.181; 95%CI, -2.625 to 0.263) in diabetic patients without DR.BCVA was significantly increased at postoperative 1 month (SMD, 1.149; 95%CI, 0.251 to 2.047; and SMD,1.349; 95%CI, 0.264 to 2.434, respectively) and 6 months (SMD, 1.295; 95%CI, 0.494 to 2.096; and SMD, 2.146; 95%CI, 0.172 to 4.120, respectively) in both diabetic patients without DR and diabetic patients with NPDR. Sensitivity analysis showed that the results were relatively stable and reliable.ConclusionUncomplicated phacoemulsification in diabetic patients with mild to moderate NPDR seemed to influence significantly the subclinical thickening of the macular zones at postoperative 1, 3 and 6 months compared with diabetic patients without DR. BCVA was significantly improved in both diabetic patients without DR and diabetic patients with mild to moderate NPDR.     

玻璃体腔注药联合微创玻璃体切除治疗糖尿病视网膜病变的临床疗效研究

目的:探讨玻璃体腔注药联合微创玻璃体切除治疗糖尿病视网膜病变的临床疗效。方法:选择2014年1月至2016年1月在我院确诊并治疗的增生性糖尿病视网膜病变患者80例,共83只患眼,随机分为A、B两组。A组共42例患眼,接受25 G玻璃体微创手术;B组共41例患眼,在A组治疗的基础上给予玻璃体腔注射康柏西普。比较两组患者的手术情况、治疗前后最佳视力的矫正(Best-corrected visual acuity,BCVA)情况、视网膜厚度以及术后1个月不良反应的发生情况。结果:B组患者的手术时间较A组显著缩短(P0.05),且术中使用电凝的患眼、术中出血以及术中发生医源性裂隙的患眼比例显著低于A组(P0.05),新生血管消失的患眼比例显著高于A组(P0.05)。B组患者术后1个月和3个月的BVCA显著高于A组(P0.05),且术后视网膜的厚度显著薄于A组(P0.05),术后发生玻璃体积血和前方出血的患眼比例显著低于A组(P0.05)。结论:玻璃体腔注射康柏西普联合25G玻璃体微创切除术治疗增生性糖尿病视网膜病变的临床疗效显著,有利于患者术后视力以及视网膜恢复。     

A Multi-Branch Convolutional Neural Network for Screening and Staging of Diabetic Retinopathy Based on Wide-Field Optical Coherence Tomography Angiography

BackgroundDiabetic retinopathy (DR) is one of the major causes of blindness in adults suffering from diabetes. With the development of wide-field optical coherence tomography angiography (WF-OCTA), it is to become a gold standard for diagnosing DR. The demand for automated DR diagnosis system based on OCTA images have been fostered due to large diabetic population and pervasiveness of retinopathy cases.Materials and methodsIn this study, 288 diabetic patients and 97 healthy people were imaged by the swept-source optical coherence tomography (SS-OCT) with 12 mm × 12 mm single scan centered on the fovea. A multi-branch convolutional neural network (CNN) was proposed to classify WF-OCTA images into four grades: no DR, mild non-proliferative diabetic retinopathy (NPDR), moderate to severe NPDR, and proliferative diabetic retinopathy (PDR).ResultsThe proposed model achieved a classification accuracy of 96.11%, sensitivity of 98.08% and specificity of 89.43% in detecting DR. The accuracy of the model for DR staging is 90.56%, which is higher than that of other mainstream convolution neural network models.ConclusionThis technology enables early diagnosis and objective tracking of disease progression, which may be useful for optimal treatment to reduce vision loss.     

Relationship between C-Reactive Protein Level and Diabetic Retinopathy: A Systematic Review and Meta-Analysis

Objectives

To date, the relationship between C-reactive protein (CRP) level and diabetic retinopathy (DR) remains controversial. Therefore, a systematic review and meta-analysis was used to reveal the potential relationship between CRP level and DR.

Methods

A systematic search of PubMed, Embase.com, and Web of Science was performed to identify all comparative studies that compared the CRP level of two groups (case group and control group). We defined that diabetic patients without retinopathy and /or matched healthy persons constituted the control group, and patients with DR were the case group.

Results

Two cross sectional studies and twenty case control studies including a total of 3679 participants were identified. After pooling the data from all 22 studies, obvious heterogeneity existed between the studies, so a subgroup analysis and sensitivity analysis were performed. Removing the sensitivity studies, the blood CRP levels in the case group were observed to be higher than those in the control group [SMD = 0.22, 95% confidence interval (CI), 0.11–0.34], and the blood CRP levels in the proliferative diabetic retinopathy (PDR) group were also higher than those in the non-proliferative diabetic retinopathy (NPDR) group [SMD = 0.50, 95% CI, 0.30–0.70].

Conclusions

The results from this current meta-analysis indicate that the CRP level might be used as a biomarker to determine the severity of DR.     

细菌脂多糖(LPS)在糖尿病视网膜微血管病变中的作用

本研究旨在通过Akita小鼠糖尿病模型及糖尿病人群血浆样本,探讨病原体相关性分子细菌脂多糖(lipopolysaccharide,LPS)在糖尿病视网膜病变中的重要作用。本研究选择6个月糖尿病病程的Akita小鼠(Ins2+/Akita)及其同年龄组野生型(wild type,WT)小鼠(C57BL/6J)尾静脉内注射脂多糖(LPS)或生理盐水对照共7 d,从影像学、电生理及病理学水平评估糖尿病视网膜眼病进展。最后收集糖尿病视网膜眼病患者及对照人群血标本,通过ELISA测定血浆LPS表达水平。通过光学相干断层扫描技术分析,发现Akita小鼠的视网膜层间厚度较WT小鼠组相比明显变薄(p=0.000 2),LPS处理进一步加重糖尿病小鼠视网膜结构损害(p=0.000 7)。视网膜电图检测发现LPS处理Akita小鼠组的视网膜细胞幅值较生理盐水处理Akita小鼠显著减慢,有统计学意义(p<0.05)。胰酶消化法分离及PAS染色小鼠眼球视网膜微血管网后,计数测得LPS处理显著增加了Akita小鼠视网膜中无细胞毛细血管数量(p=0.002 6),提示LPS在糖尿病微血管损伤中的重要作用。为保证该研究的临床转化性,我们进一步检测了糖尿病视网膜病变患者(n=19)、糖尿病患者(无微血管并发症)(n=23)及健康对照组(n=20)的血浆LPS水平,发现糖尿病患者血浆LPS水平较健康对照组显著升高(p=0.002 3),其中糖尿病视网膜病变患者LPS升高最为显著(p<0.000 1)。本研究表明,循环中细菌脂多糖增加在糖尿病视网膜病变进展中起到重要作用。     

康柏西普在糖尿病大鼠早期视网膜病变中的作用及对VEGF、ICAM-1及CRP的影响

摘要 目的：探讨康柏西普在糖尿病大鼠早期视网膜病变中的作用及对血管内皮生长因子 (vascular endothelial growth factor,VEGF)和细胞间粘附分子-1(Intercellular adhesion molecule-1,ICAM-1)及C-反应蛋白(C-reactive protein,CRP)的影响。方法：糖尿病大鼠早期视网膜病变模型(n=27)随机平分为三组-模型组、替米沙坦组与康柏西普组,造模成功后当天三组分别给予注射生理盐水、替米沙坦、康柏西普治疗,1次/w,持续4 w,检测VEGF、ICAM-1及CRP表达情况。结果：大鼠造模成功后均出现食欲增多、饮水、尿量、体重减轻的现象。替米沙坦组与康柏西普组治疗第1 w与第4 w的体重高于模型组(P<0.05),康柏西普组高于替米沙坦组(P<0.05)。替米沙坦组与康柏西普组治疗第1 w与第4 w的空腹血糖低于模型组(P<0.05),康柏西普组低于替米沙坦组(P<0.05)。替米沙坦组与康柏西普组治疗第4 w的视网膜VEGF、ICAM-1、CRP蛋白相对表达水平低于模型组(P<0.05),康柏西普组低于替米沙坦组(P<0.05)。康柏西普组视网膜厚度变薄不明显,内、外核层细胞排列整齐,神经纤维层未见明显空泡样变性。结论：康柏西普在糖尿病大鼠早期视网膜病变中的应用能抑制VEGF、ICAM-1及CRP的表达,能促进降低血糖,增加大鼠体重。     

Integrin-Linked Kinase Inhibition Attenuates Permeability of the Streptozotocin-Induced Diabetic Rat Retina

Integrin-linked kinase (ILK), as a multi-functional regulator, has been associated with diabetic retinopathy (DR). In this study, we investigated whether inhibition of ILK could result in therapeutic effects. Diabetes mellitus’s rats were induced by streptozotocin (STZ) injection. After 1 weeks induction, rats were injected intraperitoneally daily with ILK inhibitor, QLT0267, at 5 mg/kg. Then, the rats were examined by 4, 8, and 12 weeks after first STZ injection. We found that QLT0267 treatment could not only lower ILK level in retina at as early as 3 weeks after the onset of diabetes but also attenuate retina permeability, which was measured by Evan’s blue. Maximum effect was found in 11 weeks treatment. Meanwhile, QLT0267 did not disturbed blood glucose concentration. Furthermore, QLT0267 inhibited Akt (Ser473) activation and reduced expression of HIF1α and VEGF which were evaluated by western blot, real time PCR, and immunohistochemistry. We conclude that ILK may be a new target for DR.