细胞外基质纤维连接蛋白和层粘连蛋白在糖尿病大鼠视网膜微血管病变表达的研究

目的　探讨细胞外基质纤维连接蛋白 (FN )、层粘连蛋白 (LN )与糖尿病视网膜病变(DR)的关系。　方法　雄性Wistar大鼠 3 0只 ,随机分为糖尿病模型组 (DR组 ,n =2 0 )及正常对照组 (对照组 ,n =10 )。DR组大鼠腹腔注射链脲佐菌素 (STZ) 60mg/kg ,制备DR微血管病变模型。180d时处死大鼠 ,取外周血作血液流变学检查 ,眼球用 3 %胰酶消化 ,制成视网膜血管铺片 ,进行FN、LN免疫组织化学染色 ,并采用LEICA—Q550IW计算机图像分析系统定量分析FN、LN在视网膜微血管中的表达及分布。观察DR的形态学改变 ,计数内皮细胞与周细胞的比例。　结果　图像分析显示 :DR组FN、LN含量表达与对照组比较差异有显著意义 (P <0 0 0 1)。形态学观察 :DR组视网膜微血管周细胞减少、内皮细胞增生与对照组比较差异有显著意义 (P <0 0 0 1) ,毛细血管瘤、无细胞毛细血管形成 ,并有较多的白细胞栓塞血管腔。血液流变学检查 :血黏度、红细胞变形能力等改变与正常对照组比较差异均有显著意义 (P <0 0 5或 0 0 1)。　结论　细胞外基质中FN、LN的过度表达 ,介导细胞与细胞及细胞与间质之间相互作用 ,促进视网膜微血管内皮细胞增生、毛细血管瘤形成 ,并导致毛细血管闭锁、基底膜增厚等病理改变 ,可能是导致DR的重要因素之一     

早期糖尿病大鼠视网膜神经细胞凋亡及胰岛素样生长因子Ⅰ的作用

早期糖尿病大鼠被随机分为正常组、糖尿病未治疗组，糖尿病胰岛素治疗组，糖尿病胰岛素样生长因子Ⅰ（ⅠGF—Ⅰ）治疗组，6周后处死大鼠，用原位末端标记法（TUNEL法）标记大鼠视网膜凋亡细胞，免疫组化法观察Bcl-2、Bax蛋白表达。结果表明ⅠGF—Ⅰ可增加Bcl-2表达、减少Bax表达，抑制视网膜神经细胞凋亡。     

酒精对大鼠血管内皮细胞的促凋亡作用

目的探讨酒精对大鼠血管内皮细胞的促凋亡作用及其机制。方法选择24只雄性健康普通级S—D大鼠，分为对照组6只和实验组18只，验组又按处死时间分为4周（实验1组）、6周（2组）、8周（3组）各6只，通过大鼠酒精灌胃制备动物实验模型，选用内皮细胞平铺、H—E染色、TUNEL和分光光度法，探讨了酒精在一定剂量、不同持续时间对大鼠血管内皮细胞的促凋亡作用及机制。结果H—E染色及TUNEL法对照组均未见凋亡细胞，而实验各组均可见凋亡细胞，实验各组和对照组MDA、T—AOC间差异有非常显著性意义（P〈0．01）。结论过量饮酒使体内氧化-抗氧化系统严重失衡，进而导致内皮细胞凋亡。     

糖尿病小鼠视网膜神经细胞的凋亡及APP17肽对其影响

目的　研究Kkay(KK)小鼠视网膜神经细胞凋亡的情况 ,并观察APP17肽对其影响。　方法　实验小鼠随机分 3组 :正常对照 (NC)组 ,糖尿病 (DM )组 ,APP17肽组。分别于 1,3个月后取眼球作视网膜组织切片 ,TUNEL法标记凋亡细胞 ,光镜观察。　结果　DM组较NC组小鼠视网膜神经细胞凋亡显著增加 (P <0 .0 1) ,APP17肽治疗能显著减少视网膜神经细胞凋亡。　结论　DM早期即有视网膜神经细胞凋亡异常增多 ;APP17肽有抑制视网膜神经细胞凋亡的作用。     

法舒地尔对大鼠蛛网膜下腔出血早期脑损伤的行为能力及海马区神经细胞凋亡的影响

目的探讨法舒地尔对大鼠实验性蛛网膜下腔出血(SAH)早期脑损伤的行为能力及海马区神经细胞凋亡的影响。方法雄性成年健康SD大鼠随机分为假手术(sham)组、蛛网膜下腔出血(SAH)组、药物(Fasudil)组,每组各8只。颈内动脉刺破法建立大鼠SAH模型,各组干预后72 h穿梭箱实验测试大鼠行为能力,麻醉处死,海马区组织进行HE染色观察细胞形态,TUNEL染色观察凋亡细胞数量。结果对比sham组,SAH组逃避反应时间(ERT)延长,主动回避反应率(AARR)降低,海马区HE染色正常神经细胞较少,TUNEL染色表达细胞增多,差异均有统计学意义(均P0.05)。对比SAH组,Fasudil组ERT缩短,AARR升高,海马区HE染色正常神经细胞较多,TUNEL染色表达细胞减少,差异均有统计学意义(P0.05)。结论 SAH后大鼠行为能力较差,海马区神经细胞凋亡明显。法舒地尔可减轻早期脑损伤,减少神经细胞的凋亡,改善大鼠的行为能力。     

20(S)人参皂苷Rg3对糖尿病大鼠肾小管上皮细胞TGF-β1表达及凋亡的影响

目的观察20(S)人参皂苷Rg3对糖尿病大鼠肾小管上皮细胞转化生长因子(TGF)-β1表达及凋亡的影响。方法利用高糖高脂喂养联合腹腔注射链脲佐菌素(STZ)建立糖尿病大鼠模型。实验分为正常对照组、糖尿病组和Rg3治疗组。Rg3治疗组以20 mg/kg体重每日灌胃给予人参皂苷Rg3。监测大鼠体重和血糖,于12 w结束实验时处死大鼠,留取肾脏。用过碘酸雪夫(PAS)染色检测各实验组大鼠肾脏组织,观察其形态学改变;免疫组化法检测各实验组大鼠肾脏组织中TGF-β1的表达;TUNEL染色观察各实验组大鼠肾脏组织凋亡的情况。结果通过PAS染色可以观察到糖尿病组大鼠肾脏组织中肾小球毛细血管袢开放尚可,部分肾小球体积增大、囊腔裂隙变窄,肾小球系膜基质和系膜细胞弥漫性增生。Rg3治疗组大鼠肾脏组织中肾小球形态接近正常。各实验组大鼠肾脏组织中,TGF-β1均主要表达于肾小管上皮细胞,其中糖尿病组TGF-β1的表达增高,与对照组比较差异有统计学意义(P0.05);Rg3治疗组TGF-β1的表达较糖尿病组明显降低(P0.05),与正常对照组比较差异无统计学意义(P0.05)。TUNEL染色见糖尿病组肾小管上皮细胞大量凋亡,显著高于对照组与Rg3治疗组;Rg3治疗组与正常对照组之间凋亡阳性率差异有统计学意义(P0.05)。相关性分析结果显示,肾小管上皮细胞TGF-β1的表达与细胞凋亡率呈正相关。结论 20(S)人参皂苷Rg3显著抑制了糖尿病大鼠肾小管上皮细胞的凋亡,这与其下调肾小管上皮细胞TGF-β1的表达相关,该研究证实了20(S)人参皂苷Rg3对糖尿病大鼠肾脏的保护作用。     

糖尿病大鼠冠状动脉内皮细胞凋亡的研究

目的　探讨糖尿病大鼠冠状动脉内皮细胞(下称内皮细胞)凋亡的机制,以及凋亡与Fas基因、bcl-2基因表达之间的关系。　方法　实验大鼠分为未治疗组、胰岛素治疗组和正常对照组,每组8只,分别于第0周和第16周时处死检测一般指标,并观察内皮细胞的凋亡百分数(TUNEL法)、bcl-2基因、Fas基因的表达(免疫组化法)、内皮细胞超微结构的改变(电镜)。　结果　(1)16 周时,未治疗组比治疗组、正常对照组大鼠体重减轻,差异有统计学意义(P<0.05);血糖及糖化血红蛋白(HbA1c)显著高于后两组(P<0.05),内皮细胞凋亡数目明显增加,差异有统计学意义(P<0.05)。未治疗组Fas基因表达增加,而 bcl-2 基因表达降低,差异有统计学意义(P<0.01)。未治疗组可观察到较明显的内皮细胞凋亡的形态学改变。　结论　高血糖是实验大鼠内皮细胞凋亡强烈相关因素,凋亡的发生与Fas基因表达上调、bcl-2基因表达降低相关。     

前列腺素E1对糖尿病肾病大鼠肾功能及肾组织细胞凋亡的影响

目的观察前列腺素E1(PGE1)对糖尿病肾病(DN)大鼠肾功能及肾组织细胞凋亡的影响。方法雄性Wistar大鼠65只,其中55只采用单次腹腔注射链脲佐菌素(STZ)制备DN大鼠模型。将造模成功的46只大鼠随机分为4组。P组予凯时10μg/(kg.d)尾静脉静注,连续10 d。A组予洛汀新10 mg/d,灌胃8周。P+A组同时给予上述两种药物,用法同上。DN组仅给予相同体积生理盐水。10只不造模的大鼠为正常对照组,处理同DN组。8周后处死所有动物,测定24 h尿白蛋白、BUN、血肌酐(sCr),同时取肾组织行HE染色行形态学观察,采用TUNEL法染色观察细胞凋亡情况。结果治疗后8周,DN组尿白蛋白水平显著高于N组(P<0.01),各用药组尿白蛋白水平显著低于DN组(P<0.01)。各用药组的BUN、sCr水平均低于DN组(P<0.01或P<0.05。DN组出现肾脏损伤的病理改变,而各用药组病理改变较DN组减轻。TUNEL检测可见在肾小球区域细胞凋亡不明显,不同组之间凋亡细胞数无统计学差异。肾小管区域细胞凋亡明显,细胞凋亡数显著多于肾小球。结论 PGE1可以明显减少DN大鼠尿蛋白排泄,降低血清BUN、sCr,减少肾小管细胞凋亡,但对肾小球细胞凋亡无明显影响。     

针灸对2型糖尿病胰岛β细胞凋亡的影响

目的 探讨针灸对2型糖尿病胰岛β细胞凋亡的影响及作用机制.方法 将造模成功的大鼠按随机化原则分为针刺组、用药组、安慰剂组,同时将普食大鼠作为正常对照组,每组各10只.针刺组大鼠取"后三里"(相当于足三里)、内庭和胰俞穴给予针刺治疗,用药组用罗格列酮(0.2 mg/kg体重)灌胃,安慰剂组用生理盐水(2 ml/kg体重)灌胃,均1次/d,连续4 w.观察治疗前后空腹血糖变化;实验结束时,HE染色观察大鼠胰腺组织学改变,免疫组化标记胰岛β细胞,末端脱氧核糖核酸缺口标记法(TUNEL)+免疫组化法标记凋亡的胰岛β细胞.结果 针刺组、用药组胰岛β细胞凋亡率均明显低于安慰剂组(P＜0.01),针刺组胰岛β细胞凋亡率有低于用药组的趋势,但无显著性差异(P＞0.05).结论 针刺可有效抑制2型糖尿病大鼠胰岛β细胞的凋亡.     

槲皮素腹腔注射对大鼠视网膜缺血再灌注损伤的影响及其机制

目的 观察槲皮素（QU）腹腔注射对大鼠视网膜缺血再灌注损伤（RIRI）的影响并探讨其机制。方法 96只成年雄性无眼疾SPF级大鼠采用随机数字法分为对照组6只，RIRI组、阴性对照组及QU组各30只。QU组于建模前连续7 d及建模前10 min腹腔注射QU,RIRI组、阴性对照组分别腹腔注射等量生理盐水及阴性对照溶剂DMSO，对照组不作任何处理。除对照组外，RIRI组、QU组及阴性对照组均采用升高眼压法建立RIRI模型。分别于建模后6、12、24、48、72 h制作大鼠视网膜组织标本，采用HE染色观察大鼠视网膜组织形态变化，计算机图像分析系统测量大鼠视网膜组织内层厚度。采用TUNEL法观察视网膜组织细胞凋亡情况，免疫组织化学染色检测视网膜组织半胱氨酸天冬氨酸蛋白酶3(Caspase-3)表达。结果 对照组大鼠视网膜细胞形态及各层分界均正常；RIRI组、阴性对照组大鼠建模6 h后视网膜呈高度水肿，12 h后视网膜神经节细胞数目减少、神经节细胞及内核层细胞排列紊乱，24 h后视网膜水肿较前有所减轻、细胞结构遭到进一步破坏，48 h后可见视网膜水肿基本消失且神经节细胞数、内核层细胞数减少；QU...     

链脲佐菌素诱导2型糖尿病大鼠的心肌损伤观察及机制初探

目的观察链脲佐菌素（STZ）诱导2型糖尿病后不同时期大鼠心肌损伤及凋亡的程度,并对其机制进行分析。方法使用高糖、高脂加STZ注射造成大鼠2型糖尿病模型,于STZ注射后不同时间点分批处死动物,对心肌损伤及凋亡指标进行测定。结果糖尿病大鼠经STZ处理1周后,与对照组大鼠相比,空腹血糖明显升高（FBG≥16．7mmol／L）,而血清胰岛素含量升高或无明显变化,提示2型糖尿病造模成功。糖尿病大鼠第12周起LVSP、＋dp／dtmax、-dp／dtmax显著降低,提示糖尿病可引起心功能下降。糖尿病大鼠第2周、4周和12周CK—MB明显增高,第12周和24周cTnI明显增高,提示糖尿病第2周即可诱发心肌损伤,并随着病程的发展加重。凋亡指标测定表明,糖尿病大鼠在第4周和12周时,caspase-3和caspase-8活性显著增高,第12周和24周时caspase-9活性显著增高,提示糖尿病第4周即可造成心肌细胞凋亡,且可能依赖caspase-8途径早于依赖caspase-9途径。结论糖尿病可以引起心肌损伤和细胞凋亡,并随病程的延长而加重,这种凋亡与caspase-8和caspase-9依赖的凋亡途径有关。     

Diabetes induces IL-17A-Act1-FADD-dependent retinal endothelial cell death and capillary degeneration

PurposeDiabetes leads to progressive complications such as diabetic retinopathy, which is the leading cause of blindness within the working-age population worldwide. Interleukin (IL)-17A is a cytokine that promotes and progresses diabetes. The objective of this study was to determine the role of IL-17A in retinal capillary degeneration, and to identify the mechanism that induces retinal endothelial cell death. These are clinically meaningful abnormalities that characterize early-stage non-proliferative diabetic retinopathy.MethodsRetinal capillary degeneration was examined in vivo using the streptozotocin (STZ) diabetes murine model. Diabetic-hyperglycemia was sustained for an 8-month period in wild type (C57BL/6) and IL-17A^?/? mice to elucidate the role of IL-17A in retinal capillary degeneration. Further, ex vivo studies were performed in retinal endothelial cells to identify the IL-17A-dependent mechanism that induces cell death.ResultsIt was determined that diabetes-induced retinal capillary degeneration was significantly lower in IL-17A^?/? mice. Further, retinal endothelial cell death occurred through an IL-17A/IL-17R ? Act1/FADD signaling cascade, which caused caspase-mediated apoptosis.ConclusionThese are the first findings that establish a pathologic role for IL-17A in retinal capillary degeneration. Further, a novel IL-17A-dependent apoptotic mechanism was discovered, which identifies potential therapeutic targets for the early onset of diabetic retinopathy.     

氨基胍对糖尿病大鼠视网膜神经细胞改变及caspase-3表达的影响

目的观察早期糖尿病大鼠视网膜神经细胞结构变化、caspase-3表达及氨基胍的治疗作用。方法健康成年Wistar大鼠50只,12只作为正常对照组,其他大鼠链脲佐菌素(streptozotocin,STZ)腹腔注射建立糖尿病(DM)大鼠模型,并随机分为氨基胍治疗组及DM模型组,每组又按时间分为1、3、6个月组。透射电镜下观察视网膜超微结构改变,免疫组织化学法检测视网膜组织caspase-3蛋白的表达变化。结果电镜变化:模型1个月组内核层细胞胞质出现不均匀现象;3个月组内核层细胞核个别染色质出现浓缩现象,神经节细胞亦出现超微结构的变化;6个月组上述变化进一步加重,并可在内核层及神经节细胞层发现个别凋亡小体,氨基胍治疗组变化较糖尿病组轻微。免疫组织化学表达:模型3个月组caspase-3蛋白开始表达,主要见于神经节细胞层;模型6个月组阳性表达进一步增加,扩展到内核层。氨基胍组caspase-3表达变化规律与模型组基本一致,治疗组3个月、6个月阳性表达均分别低于未治疗组(P<0·05)。结论早期DM大鼠视网膜出现了电镜组织学改变,caspase-3参与了糖尿病视网膜病变的发病机制。氨基胍对糖尿病视网膜病变有一定的治疗作用。     

糖尿病不同病程大鼠背根神经节和坐骨神经细胞凋亡的研究

目的 研究糖尿病大鼠不同病程背根神经节神经元和坐骨神经细胞的凋亡。方法尾静脉内注射链脲佐菌素诱导建立糖尿病大鼠模型。应用TUNEL法观察糖尿病不同病程大鼠背根神经节神经元和坐骨神经细胞的凋亡情况。结果糖尿病1个月、3个月和6个月时背根神经节神经元和坐骨神经施万细胞的凋亡细胞数与同期对照组相比明显增加（背根神经节分别为3．5％、5．2％和8．5％,坐骨神经分别为3．8％、5．5％和9．8％）,并且随着糖尿病病程的延长,细胞凋亡加重。结论在糖尿病早期背根神经节和坐骨神经即已存在细胞凋亡增加,细胞凋亡在糖尿病神经病变中起着重要作用。     

Aging increases retinal vascular lesions characteristic of early diabetic retinopathy

The goal of this study was to determine whether aging induces retinal vascular lesions that are similar to those seen in diabetic retinopathy. Female rats were randomly divided into four groups; each group represented a time point and consisted of four non-diabetic rats and four diabetic rats. At time points of 3, 12, 18, or 22 months of age, retinas were isolated and subjected to retinal trypsin digestion (RTD) for isolation of retinal capillary networks. Blood glucose, body weight, and hemoglobin A1c (HbA1c) levels were monitored throughout the study. One RTD from each animal was stained with Hematoxylin and Periodic Acid Schiff’s (PAS) reagent to analyze acellular capillaries and pericyte loss, while the contralateral RTD from each animal was subjected to TUNEL assay to assess apoptosis in the retinal vascular cells. The numbers of acellular capillaries and pericyte loss were significantly increased between the 12 vs. 18 month groups, and the 18 vs. 22 month groups. Similarly, acellular capillaries and pericyte loss increased with aging in the diabetic rat retinas; however, the appearance of acellular capillaries and pericyte loss occurred at 3 months of diabetes. TUNEL assay showed increased apoptosis associated with acellular capillaries and pericyte loss in both normal, aged rats and diabetic rats. In conclusion, retinal vascular lesions that develop in aged rat retinas have striking similarities to those of diabetic rat retinas. The breakdown of normal vascular architecture with aging appears to have resemblance with the anatomical and histological lesions associated with diabetic retinopathy.     

Expression and significance of HIF-1α and VEGF in rats with diabetic retinopathy

Objective:To investigate the expression of hypoxia inducible iaclor-1α(HIF-1α)and vascular endothelial growth factor(VECF)in diabelic retinopathy(DR)rats and its effect on the DR occurrence and development.Methods:A total of 120 SD rats were randomly divided into trial group and control group with 60 in each.STZ.i.p.was used in the trial group to establish the DM model,citrate buffer salt of same amount was used up.to the control group.1,3 and 6 months after injection,respective 20 rats were sacrificed in each group to observe expression of HIF-1αand VEGF in the rat retina tissue at different lime points.Results:Expression of HIF-1αand VEGF were negative in the control group;expression of HIF-1αand VKGF protein in retinal tissue were weak after 1 month of DR mold formation.It showed progressive enhancement along with the progression in different organizations,differences between groups were significant(P0.05).Conclusions:Expressions of HIF-1αand VF.GF were;correlated with disease progression in early diabelic relinopathy.Retinal oxygen can induce over-expression of HIF-1αand VEGF.It shows that HIF-1αand VEGF play an important role in the pathogenesis of DR.     

Chronic changes of the iris microvasculature of streptozotocin-induced diabetic rats using fluorescence videomicroscopy

This study was aimed to investigate chronic changes of the iris microvasculature in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in male Wistar-Furth rats by intravenous injection of STZ (55 mg/kg.bw). The rats were divided into control (CON) and diabetic (STZ) groups. The experiments were performed at 8, 12, 24 and 36 weeks after the injection of STZ. The iris microcirculation was visualized under a fluorescence videomicroscope. Intraluminal diameters of microvessels were measured based on the FITC-dextran images. Leukocyte adhesion to the microvascular endothelium was evaluated by counting leukocytes (labeled with rhodamine 6G). The iris blood perfusion was measured using laser Doppler flowmetry. Tissue lipid peroxidation of the eye was evaluated. The results demonstrated that the lipid peroxidation increased significantly after the injection of STZ. Both the diameters of arterioles (or precapillaries) and the iris blood perfusion decreased significantly in STZ rats, compared to the control levels. Adherent leukocytes increased significantly at 8, 12, 24 and 36 week after the injection of STZ, compared with the control levels. This indicates that the increased in oxygen-derived free radicals may be a major contributor for iris vascular endothelial dysfunction in diabetes mellitus, including leukocyte adhesion and reducing the arteriolar diameter. The present model may be useful for assessing long-term effects of therapeutic agents on diabetic retinopathy.     

阿托伐他汀对糖尿病大鼠内皮祖细胞及视网膜病变影响的研究

目的探讨他汀类药物对糖尿病大鼠循环内皮祖细胞（EPCs）及视网膜病变的影响及作用机制。方法成年Wistar大鼠150只,随机分为2组。正常对照组（阴性组）,糖尿病组（阳性组）。注射链尿佐菌素（STZ）,造糖尿病大鼠模型。将糖尿病大鼠再随机分为3组：低剂量组（他汀10mg／Kg·d）,高剂量组（他汀20mg／Kg·d）,单纯糖尿病组。灌胃给药,对照组及单纯糖尿病组给予等量生理盐水。大鼠分别于3个月,6个月时按比例随机处死。取动脉血检测EPCs数量、取眼球固定后观察视网膜血管内皮生长因子（VEGF）蛋白表达情况。结果糖尿病大鼠造模成功率81％。3个月及6个月时,低剂量组存活率均较高剂量组及单纯糖尿病组有所增加（P〈0．05）。他汀类药物促进EPCs数量上升,低剂量组与对照组、糖尿病组、高剂量组比较,3个月及6个月时各组间均有统计学意义（P〉0．05）,高剂量组与对照组及糖尿病组比较无统计学差异（P〈0．05）。不同剂量的他汀类药物对视网膜VEGF蛋白表达情况：糖尿病组VEGF免疫阳性表达最强,高剂量组VEGF免疫阳性表达比糖尿病组减弱,低剂量治疗组VEGF免疫阳性表达最低。结论他汀类药物能够促进EPCs数量增加。小剂量他汀类药物可抑制糖尿病大鼠视网膜VEGF表达,减缓视网膜病变进展;并降低糖尿病大鼠的死亡率。     

Long-term effects of oral vitamin C supplementation on the endothelial dysfunction in the iris microvessels of diabetic rats

The current study was aimed to investigate effects of long-term supplementation of vitamin C on the iris microcirculation in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in male Wistar-Furth rats by intravenous injection of STZ (55 mg/kg b.w.). The rats were divided into three groups: control rats (CON), STZ-induced diabetic rats (STZ), and STZ rats supplemented with vitamin C (STZ-vitC). For supplementation of vitamin C, ascorbic acid (1 g/l) was added into the drinking water. The experiments were performed at different periods (8, 12, 24 and 36 weeks) after injection of STZ. Blood glucose, tissue lipid peroxidation and plasma vitamin C were measured. To examine the endothelial function, leukocyte adhesion to the venular endothelium was evaluated in the iris post-capillaries by means of counting the number of leukocytes labeled with rhodamine 6G. Blood flow perfusion in the iris was monitored using a laser Doppler flow meter. In the STZ rats, hyperglycemia was induced with an increase in HbA(1c) and lipid peroxidation but with a decrease in the plasma vitamin C level which improved by vitamin C supplementation. The number of adherent leukocytes increased significantly, associated with reduction in the iris blood flow perfusion, at 8, 12, 24 and 36 weeks after injection of STZ. In the STZ-vitC rats, the iris blood flow perfusion was significantly increased in comparison with the STZ rats, while the leukocyte adhesion was decreased at 24 and 36 weeks. The statistical analysis shows that the leukocyte adhesion decreased with increase in the iris blood flow perfusion in STZ and STZ-vitC rats. In conclusion, vitamin supplementation suppressed leukocyte adhesion and thus endothelial dysfunction, associated with increase in iris blood flow perfusion in diabetes. The antioxidant vitamin C may be a therapeutic agent for preventing diabetic retinopathy.