核运输因子2在糖尿病大鼠视网膜的时空表达及其意义

目的:探讨糖尿病大鼠视网膜中核运输因子2(NTF2)的时空表达变化及意义。方法:伊凡思蓝(EB)灌注铺片观察糖尿病大鼠视网膜血管分布和形态。逆转录-聚合酶链式反应(RT-PCR)检测与糖尿病大鼠不同时点鼠龄匹配的对照组(N2w,N1m,N3m,N6m)和糖尿病成模后2周、1月、3月、6月(D2w,D1m,D3m,D6m)大鼠视网膜中NTF2、血管内皮生长因子(VEGF)mRNA的表达。免疫组化法检测NTF2蛋白在视网膜中的表达和分布位置。结果:正常组大鼠可见在低背景荧光下视网膜血管对EB有很好的屏障作用,成模1月后糖尿病大鼠视网膜血管仅见背景荧光增强,成模3月后血管出现异常节段性扩张,局部血管周围EB渗漏。与糖尿病大鼠年龄匹配的正常大鼠视网膜NTF2和VEGF并未随时间延长而变化,mRNA表达稳定。糖尿病成模2周后开始,NTF2mRNA有轻度增高,并随病程的延长保持较高水平,病程达6个月时,NTF2表达开始回落,与正常大鼠基本一致。NTF2蛋白在正常大鼠及糖尿病大鼠视网膜中免疫组化均可以检出,主要分布在视网膜内层,以节细胞层、内核层为主。结论:NTF2mRNA水平在糖尿病大鼠视网膜中升高,主要分布在视网膜内层。NTF2很可能在糖尿病视网膜病变中起着一定的调控作用,其作用途径及机制可能与VEGF的作用通路有一定的联系。     

伊文思蓝检测急性高眼压后大鼠血-视网膜屏障的变化

目的:检测急性高眼压后大鼠血-视网膜屏障(BRB)的改变.方法:大鼠随机分为正常对照组、实验对照组和实验组（急性高眼压模型）.动物分别存活3h、12 h、1d、3d、7d,处死前注射伊文思蓝(EB),共聚焦显微镜检测视网膜铺片和切片中EB的分布;用分光光度计定量视网膜EB的含量.结果:在急性高眼压后视网膜中可见,EB红...     

NgR/NR2B信号通路对糖尿病大鼠视网膜神经节细胞的影响

目的:探讨Nogo受体(NgR)在糖尿病视网膜病变中的作用及下游分子机制。方法:雄性SD大鼠腹腔注射链脲佐菌素诱导糖尿病模型,糖尿病大鼠玻璃体腔内注射病毒包装的NgR反义核苷酸序列(siNgR组)、阴性核苷酸序列(scRNA对照组)或空白病毒液(糖尿病组),玻璃体腔内注射空白病毒液的正常SD大鼠为正常对照组。3个月视网膜HE染色,观察视网膜神经层厚度及节细胞密度的变化,免疫荧光组化检测NgR及其下游分子N-甲基-D-天门冬氨酸2B受体(NR2B)在视网膜神经节细胞内的共存情况,Western Blot检测NgR及NR2B在视网膜内的表达。结果:与正常对照组相比糖尿病组及scRNA对照组视网膜明显变薄、神经节细胞密度降低,siNgR组无明显变化。NgR与NR2B均表达于视网膜节细胞层,二者在视网膜神经节细胞内大量共存。与正常对照组相比,糖尿病组、scRNA对照组视网膜NgR及NR2B表达均明显增加(P0.01),而siNgR组NgR及NR2B表达均无明显变化。结论:NgR/NR2B信号通路激活可能是糖尿病大鼠RGC数量减少的重要原因之一。     

早期糖尿病视网膜病变模型大鼠玻璃体腔注射安维汀后房水细胞因子变化

背景：关于抑制血管生成药安维汀治疗早期糖尿病视网膜病变大鼠的机制研究多数局限于血管内皮生长因子,而结缔组织生长因子和色素上皮衍生因子也在其中起重要的作用。 目的：探讨安维汀玻璃体腔注射在早期糖尿病视网膜病变模型大鼠应用后房水细胞因子的变化及意义。 方法：经链脲佐菌素诱导10周建立早期糖尿病视网膜病变模型大鼠,分别采用安维汀(1.25,2.5 mg)和生理盐水进行玻璃体腔注射。 结果与结论：ELISA检测显示,与生理盐水注射组比较,两个安维汀注射组房水中血管内皮生长因子质量浓度降低,色素上皮衍生因子和结缔组织生长因子质量浓度增高(P < 0.05),但两组间上述细胞因子的浓度差异无显著性意义(P > 0.05)。结果证实,安维汀玻璃体腔注射在早期糖尿病视网膜病变大鼠应用促进新生血管的细胞因子血管内皮生长因子水平降低,抑制新生血管的细胞因子色素上皮衍生因子质量浓度升高,促进结缔组织生长因子水平升高。 中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程全文链接：     

微量元素铜/锌比值对糖尿病大鼠视网膜病变的影响

目的 探讨铜／锌（Cu／Zn）比值与糖尿病大鼠视网膜病变的关系，观察适量补Zn并使Cu／Zn比值下降对糖尿病大鼠视网膜病变的影响。方法 将雄性SD大鼠40只随机分为四组，即正常对照组、模型对照组、实验Ⅰ组和实验Ⅱ组。按60mg／kg体质量尾静脉注射链脲佐菌素（STZ）以制造糖尿病大鼠模型。实验Ⅰ组、Ⅱ组分别以葡萄糖酸锌每日Zn^2＋6mg／kg体质量（浓度为0．12mg／ml/kg）和每日Zn^2＋3mg／kg体质量（浓度为0．06mg／ml／kg）用水溶解后单笼喂养。模型对照组、正常对照组饮用自来水。实验周期3个月，采尾血测血糖（BS），再从颈总动脉取血分别测定血清Cu、Zn含量，并计算出Cu／Zn比值。双眼灌流后制作视网膜血管铺片，铺片行PAS染色，光镜下观察大鼠视网膜毛细血管结构。结果 ①实验Ⅰ组血清Zn和Cu／Zn比值接近或超过正常对照组。与模型对照组相比有显著性差异（P〈0．01）；而实验Ⅱ组的血清Zn和Cu／Zn比值与模型对照组相比差异无统计学意义。②视网膜血管铺片正常对照组可见毛细血管形态规整；模型对照组视网膜毛细血管形态发生改变。血管迂曲、扭结，部分血管闭塞。补充Zn剂后，实验Ⅰ组随着Cu／Zn比值的下降。其视网膜毛细血管形态改变较同一时期的模型对照组明显好转．而实验Ⅱ组视网膜毛细血管形态改变类似于模型组。结论对糖尿病大鼠，适量补充Zn剂使Cu／Zn比值下降，可减轻视网膜的毛细血管损伤。     

抑制血管生成药安维汀玻璃体腔注射后房水细胞因子的变化CSCD

背景:关于抑制血管生成药安维汀(Avastin)治疗增殖型糖尿病视网膜病变的机制研究大多数均局限在血管内皮生长因子本身,而结缔组织生长因子、血管增生抑制因子也在其疾病中扮演着重要的角色。目的:考察增殖性糖尿病视网膜病变玻璃体切割术前应用安维汀玻璃体腔注射前后房水细胞因子的变化。方法:选取增殖性糖尿病视网膜病变患者30例(30眼),采用随机数字表法分为3组,每组10例(10眼)。玻璃体切割组:直接行玻璃体切割手术;安维汀注射0.05 mL组:于玻璃体切割前7 d玻璃体腔注射0.05 mL安维汀(1.25 mg);安维汀注射0.1 mL组:于玻璃体切割前7 d玻璃体腔注射0.1 mL安维汀(2.5 mg)。分别于术中抽取少量房水,检查血管内皮生长因子、结缔组织生长因子及色素上皮衍生因子的表达变化。结果与结论:与玻璃体切割组比较,安维汀注射组房水中血管内皮生长因子含量降低,色素上皮衍生因子和结缔组织生长因子含量增高,并能抑制血管内皮生长因子的表达,差异有显著性意义;安维汀注射0.05 mL组与安维汀注射0.1 mL组相比,差异无显著性意义。结果说明玻璃体腔注射安维汀在增殖性糖尿病视网膜病变玻璃体切割前辅助应用可以减少与增殖相关的细胞因子的含量,同时增加了拮抗新生血管生长的细胞因子。     

定量大鼠视神经损伤模型的建立

目的：建立大鼠定量视神经损伤模型，介绍其制作方法。 方法： 健康Wistar大鼠90只，15只为正常组，只进行3%荧光金逆行标记视网膜神经节细胞，以对比正常大鼠左、右眼视网膜神经节细胞数量；另75只大鼠，其中左眼为损伤眼，右眼为未损伤眼，作为对照组，按损伤后存活时间不同分为1 d组、3 d组、7 d组、15 d组、30 d组，每组15只。应用40 g力的视神经夹在大鼠眼球后2 mm处夹视神经9 s,于处死前7 d采用双上丘注射3%荧光金标记双眼视网膜神经节细胞。取眼球标本并分离视神经至视交叉。视网膜铺片做荧光照相，并输入计算机图像分析仪计数视网膜神经节细胞。将视神经沿其长轴做切片在光镜下观察。 结果： 手术获取完整的大鼠眼球，并分离视神经至视交叉。视网膜神经节细胞计数，损伤组与对照组进行比较。正常组中，左眼195.76±36.12，右眼197.52±39.25，两者差异无显著（P＞0.05）；伤后1 d左眼165.12±26.36，右眼191.21±35.26，两者差异显著（P<0.01）；伤后3 d左眼152.26±25.12，右眼192.16±32.12, 两者差异显著（P<0.01）；伤后7 d左眼135.19±21.32,右眼189.26±26.16, 两者差异显著（P<0.01）；伤后15 d左眼123.96±27.19,右眼191.76±25.29, 两者差异显著（P<0.01）；伤后30 d左眼105.75±22.26,右眼186.56±23.76, 两者差异显著（P<0.01）。损伤眼视神经损伤后不同时间RGCs计数逐渐下降（P<0.01）；损伤处视神经肿胀、出血,胶质细胞排列紊乱,空泡样变性，随损伤后时间延长而加重。 结论： 应用40 g力视神经夹建立的定量视神经损伤动物模型是可行的,并可应用于视神经损伤修复的研究中,完整标本的获取需要较为熟练的手术技巧。     

rAAV2／1载体介导 EGFP 对大鼠骶髓转染的实验研究

以重组腺相关病毒载体（recombinant adeno -associated virus,rAAV）携带增强型绿色荧光蛋白（enhanced green fluorescent protein,EGFP）基因转染入大鼠骶髓,观察其定位及表达情况,评价其作为骶髓病变基因治疗载体的可行性。SD 大鼠经膀胱肌层多点注射 rAAV2/1-EGFP,分别按转染复数1×109、1×1010、4×1010转染。分别在2周、4周、8周后,将大鼠深麻醉,经左心室-升主动脉插管4％多聚甲醛灌注固定,慢慢剥离出脊髓,将脊髓放入含30％蔗糖的 PBS 中过夜（4℃）,然后恒温冰冻切片机内连续切片,厚度12μm,免疫荧光染色（GFP 抗体,FITC 标记山羊抗兔 IgG）后,在荧光显微镜下观察 EGFP 表达情况。荧光显微镜下显示,4周时,转染复数为4×1010的大鼠骶髓神经元表达强荧光,可见增强型绿色荧光蛋白弥散表达。rAAV2/1载体可将 EGFP 基因有效地转染入大鼠骶髓,rAAV2/1载体是一种理想的基因治疗载体,为rAAV2/1作为载体转染骶髓治疗神经源性疾病提供理论依据。     

明胶墨汁与荧光微球显示大鼠视网膜微血管灌流效果的对比研究

目的:比较明胶墨汁灌注与荧光微球灌注对大鼠视网膜微血管灌流情况的显示效果。方法:12只成年健康SD大鼠随机分成荧光微球组(6只)和明胶墨汁组(6只)。明胶墨汁组分两步经左心室灌注明胶墨汁40ml。荧光微球组经股静脉注射荧光微球0.5ml。视网膜行铺片和切片,观察荧光微球和改良墨汁灌注显示的微血管灌流情况;两组视网膜切片还进行NeuN、Parvalbumin和GFAP的免疫组化染色。结果:荧光微球零散分布于视网膜铺片周边部和中央部视的网膜血管中;不能显示铺片的血管轮廓和切片中的血管截面。荧光微球与NeuN、Parvalbumin或GFAP免疫组化双标不能在同一组织中准确显示视网膜血管与神经细胞的紧密空间关系。改良墨汁灌注能清晰显示大鼠视网膜铺片中周边部和中央部的血管网,以及切片中的血管截面,而且此方法与NeuN、Parvalbumin或GFAP免疫组化双标能在同一组织中准确显示视网膜血管与神经细胞的紧密空间关系。结论:改良明胶墨汁灌注在显示大鼠视网膜微血管灌流情况方面优于荧光微球,适宜于在视网膜疾病研究中广泛使用。     

玻璃体腔接种视网膜S抗原诱导的免疫偏离

目的：确立玻璃体腔（ＶＣ）是否具有支持针对视网膜可溶性抗原（Ｓ抗原）刺激诱地偏离式免疫反应的能力，并观察白细胞介素－１（ＩＬ－１）对玻璃体腔免疫特性的影响。方法：将视网膜Ｓ抗原接种于Ｗｉｓｔａｒ大鼠的眼前房和玻璃体腔。抗原接种后７ｄ，使用Ｓ抗原和完佐剂免疫受主动物。然后，通过足部刺激评估迟发型超敏反应（ＤＴＨ）。通过腹腔注射ＩＬ－１改变全身的免疫状态。结果：前房和玻璃体腔注射Ｓ抗原的动物没有发生原     

糖尿病大鼠视网膜色素上皮细胞超微结构

目的 :探讨糖尿病大鼠视网膜色素上皮细胞超微结构病变 ,为糖尿病视功能障碍提供有关的行态学依据。方法 :选择清洁级SD大鼠随机分成正常对照组、糖尿病 1月、3月和 6月。腹腔内注射链脲佐菌素 (STZ)诱导大鼠糖尿病 ,每组 1 2只 ,取视网膜制备超薄切片 ,透射电镜观察。处死前每月测体重、血糖 1次。结果 :糖网病大鼠视网膜色素上皮细胞的微绒毛和基底部的质膜内褶随血糖的增高病情加重而逐渐稀疏、低矮直至脱落、低平。胞质内细胞器以线粒体的脱嵴、水肿和内质网的扩张为主要损害 ,而相邻色素上皮细胞之间的连接复合体始终存在。结论 :糖网病大鼠视网膜色素上皮细胞的损害主要表现于微绒毛、质膜内褶及细胞器的损害 ,并无脉络膜与视网膜之间屏障功能的损害。本研究为糖网病的临床研究提供形态学依据     

Pim-1基因重组腺相关病毒2载体的构建及感染大鼠视网膜

目的构建携带大鼠原癌基因Pim-1的重组腺相关病毒2载体(rAAV2-Pim-1),检测其体内感染大鼠视网膜的细胞类型及目的基因Pim-1在视网膜中的表达。方法 p AOV-CAGMINI-EGFP-2A-MCS-3FLAG载体及Pim-1基因PCR产物用Nhel酶切,琼脂糖凝胶电泳鉴定后回收载体及目的基因DNA并连接转化,鉴定质粒阳性克隆及测序。rAAV2-Pim-1表达质粒p AOV-CAGMINI-EGFP-2A-Pim-1-3FLAG及包装质粒p AAV-RC和辅助质粒p Helper,通过Lipofectamine 2000共转染293细胞,纯化获得高滴度的rAAV2-Pim-1。大鼠玻璃体注射rAAV2-Pim-1,用免疫荧光组织化学检测其感染视网膜的细胞类型;用Real-time PCR和Western blotting检测Pim-1在视网膜中的表达。结果rAAV2-Pim-1质粒构建成功并且核苷酸序列比对正确;质粒转染293细胞后出现绿色荧光;包装出的病毒浓缩滴度为5.7×1015vg/L。rAAV2-Pim-1组体内感染视网膜神经节细胞(RGCs)达71%,并感染少量无长突细胞,几乎不感染星形胶质细胞;Pim-1 mRNA和蛋白在视网膜中的表达约为rAAV2-EGFP组的6.61倍和2.29倍。结论成功构建rAAV2-Pim-1病毒载体,并在感染后的大鼠视网膜RGCs中过表达Pim-1。     

Labelling of retinal microglial cells following an intravenous injection of a fluorescent dye into rats of different ages

Retinal microglia were selectively and sequentially labelled in different layers of the retina of postnatal rats following a single intravenous injection of the fluorescent dye, rhodamine isothiocyanate (RhIc). The fluorescent cells were doubly immunostained with OX-42 and ED-1 antibodies that recognise complement type 3 (CR3) receptors and macrophage antigen, respectively. RhIc was first detected in the retinal blood vessels 5 min after injection. At 1 h, a variable number of microglia in the inner layers of the retina, namely, the nerve fibre and ganglion cell layers appeared to emit weak fluorescence. Labelled microglial cells in the inner nuclear and outer plexiform layers were not detected until 1 and 2 d had elapsed following RhIc injection. The number of labelled retinal microglia was progressively increased with time, peaking at 4 d after RhIc injection. The frequency of RhIc labelled cells also increased with age, with the largest number of cells occurring in 7-d-old rats but declined thereafter. In 11 d or older rats, RhIc was confined to the retinal blood vessels. It is concluded that when injected into the circulation, RhIc could readily gain access into the retina tissues due to an inefficient blood-retina barrier in early postnatal stages. It became impeded with maturation of the blood-retina barrier, which was established between 11 and 13 d of age. RhIc that inundated the retinal tissues was thoroughly sequestered by the resident microglial cells. It is therefore suggested that the latter could play a protective role against serum-derived substances that may be deleterious to the developing retina.     

Mechanisms of leukocyte migration across the blood–retina barrier

Immune-mediated inflammation in the retina is regulated by a combination of anatomical, physiological and immuno-regulatory mechanisms, referred to as the blood–retina barrier (BRB). The BRB is thought to be part of the specialised ocular microenvironment that confers protection or “immune privilege” by deviating or suppressing destructive inflammation. The barrier between the blood circulation and the retina is maintained at two separate anatomical sites. These are the endothelial cells of the inner retinal vasculature and the retinal pigment epithelial cells on Bruch’s membrane between the fenestrated choroidal vessels and the outer retina. The structure and regulation of the tight junctions forming the physical barrier are described. For leukocyte migration across the BRB to occur, changes are needed in both the leukocytes themselves and the cells forming the barrier. We review how the blood–retina barrier is compromised in various inflammatory diseases and discuss the mechanisms controlling leukocyte subset migration into the retina in uveoretinitis in more detail. In particular, we examine the relative roles of selectins and integrins in leukocyte interactions with the vascular endothelium and the pivotal role of chemokines in selective recruitment of leukocyte subsets, triggering adhesion, diapedesis and migration of inflammatory cells into the retinal tissue.     

Acceleration of blood-brain barrier formation after transplantation of enteric glia into spinal cords of rats

Enteric glia share morphological, biochemical, and functional properties with astrocytes. Thus, like astrocytes, transplantation of enteric glia into the central nervous system (CNS) might facilitate the development of the characteristics of the blood brain barrier (BBB) in endothelial cells. This study explored this possibility by examining barrier formation after implantation into the spinal cord of rats. Phaseolus vulgaris leucoagglutin (PHAL)-treated enteric glia suspensions were injected into the spinal cord at the T11–T12 level of adult Wistar female rats. Control animals were injected with either 3T3 fibroblast, glioma C6 cells, or culture medium. Evans blue, a dye excluded by the BBB, was injected intravenously from 1 week to 2 months after implantation. Leakage of dye was determined macroscopically and the ultrastructure of the capillaries was examined. During the first week leakage of dye correlated ultrastructurally with predominantly non-overlapping endothelial cell junctions, even with clefts between adjacent cells. Tight junctions were fully formed by 2 months and no dye leaked. Electron microscopic analysis showed that enteric glia had end-feet in close contact with endothelial cells. In contrast, the injection sites in all control animals leaked dye until 2 months, and most of the tight junctions that did form were incomplete. Furthermore, most 3T3 or C6 control cells had died at 2 months and those that survived, unlike enteric glia, had no anatomical relationship to blood vessels. These data demonstrate that implantation of enteric glia accelerates the formation of the characteristics of the BBB in spinal cord capillaries.     

Neuroprotective and blood-retinal barrier-preserving effects of cannabidiol in experimental diabetes

Diabetic retinopathy is characterized by blood-retinal barrier (BRB) breakdown and neurotoxicity. These pathologies have been associated with oxidative stress and proinflammatory cytokines, which may operate by activating their downstream target p38 MAP kinase. In the present study, the protective effects of a nonpsychotropic cannabinoid, cannabidiol (CBD), were examined in streptozotocin-induced diabetic rats after 1, 2, or 4 weeks. Retinal cell death was determined by terminal dUTP nick-end labeling assay; BRB function by quantifying extravasation of bovine serum albumin-fluorescein; and oxidative stress by assays for lipid peroxidation, dichlorofluorescein fluorescence, and tyrosine nitration. Experimental diabetes induced significant increases in oxidative stress, retinal neuronal cell death, and vascular permeability. These effects were associated with increased levels of tumor necrosis factor-alpha, vascular endothelial growth factor, and intercellular adhesion molecule-1 and activation of p38 MAP kinase, as assessed by enzyme-linked immunosorbent assay, immunohistochemistry, and/or Western blot. CBD treatment significantly reduced oxidative stress; decreased the levels of tumor necrosis factor-alpha, vascular endothelial growth factor, and intercellular adhesion molecule-1; and prevented retinal cell death and vascular hyperpermeability in the diabetic retina. Consistent with these effects, CBD treatment also significantly inhibited p38 MAP kinase in the diabetic retina. These results demonstrate that CBD treatment reduces neurotoxicity, inflammation, and BRB breakdown in diabetic animals through activities that may involve inhibition of p38 MAP kinase.     

Genetic difference in susceptibility to the blood-retina barrier breakdown in diabetes and oxygen-induced retinopathy

The breakdown of the blood-retina barrier (BRB) is a common feature of diabetic retinopathy. The purpose of the present study is to determine whether there are genetic differences in susceptibility to the breakdown of the BRB in diabetic retinopathy using two rat models. In streptozotocin (STZ)-induced diabetes, Brown Norway (BN) rats developed sustained vascular hyperpermeability in the retina during the entire experimental period (16 weeks of diabetes), while diabetic Sprague Dawley (SD) rats only showed retinal hyperpermeability from 3 to 10 days after the onset of diabetes. The strain difference in permeability was not correlated with the blood glucose levels in these two strains. In oxygen-induced retinopathy (OIR), BN rats developed retinal vascular hyperpermeability from postnatal day 12 (P12) to P22 with a peak at P16, which was 8.7-fold higher than that in the age-matched normal controls. In OIR-SD rats, however, hyperpermeability was observed from P14 to P18, with a peak only 2.2-fold higher than that in the controls. The strain difference in vascular hyperpermeability was correlated with the different overexpression of vascular endothelial growth factor (VEGF) in the retina of these two models. This finding suggests that genetic backgrounds contribute to the susceptibility to diabetic retinopathy.     

PJ34对脑缺血再灌注大鼠应用rt-PA后血脑屏障完整性的影响

目的　研究多聚ADP核糖聚合酶-1（poly-ADP ribose polymerase-1,PARP-1）抑制剂PJ34能否改善脑缺血再灌注大鼠应用重组人组织型纤溶酶原激活物（recombinant tissue plasminogen activator,rt-PA）后的血脑屏障完整性。 方法　将60只大鼠随机分为假手术组、缺血再灌注（ischemia-reperfusion,IR）组、rt-PA组及PJ34组。IR组：采用改良 Zea Longa 线栓法,制备局灶性脑缺血2 h再灌注模型。PJ34组及rt-PA组：缺血2 h拔出鱼线,同时给予尾静脉注射rt-PA 10 mg/kg,腹腔注射PJ34或生理盐水3 mg/kg。进行神经功能缺损评分、伊文氏蓝测定血脑屏障通透性、免疫组化分析MMP-9、Claudin-5、ZO-1的表达。 结果　rt-PA组的神经功能缺损评分、伊文氏蓝含量及MMP-9表达均高于IR组,PJ34组低于rt-PA组,但高于IR组（P<0.05）;rt-PA组的Claudin-5、ZO-1表达低于IR组,PJ34组高于rt-PA组,但低于IR组（P<0.05）。 结论　PJ34通过抑制MMP-9的表达,增加Claudin-5、ZO-1的表达,可以有效改善脑缺血再灌注后应用rt-PA的大鼠血脑屏障完整性。     

糖尿病大鼠视网膜视细胞超微结构病理变化的研究

目的:探讨糖尿病大鼠视网膜病变（diabetic retinopathy.DR.简称糖网病）,早期视细胞（视感受器）的超微结构病变,为糖网病光感受器功能障碍提供形态学依据。方法:选择清洁级SD大鼠随机分成正常对照组（CON）、糖尿病1月（DM1）、3月（DM3）和6月（DM6）。按60mg/kg腹腔内注射链脉佐菌素（STZ）诱导大鼠糖尿病,每组12只,取大鼠视网膜透射电镜观察。处死前每月测血糖和眼底镜检查1次。结果:病程1个月:视杆、视锥细胞的外节膜盘模糊不清,膜盘间隙略有扩大,椭圆体内中心粒和纤毛仍清晰可见,线粒体规则的排列在周围。病程3个月,视细胞外节膜盘间隙明显扩大,纵横交错,排列紊乱,并发生局灶性断裂,椭圆体内有部分线粒体肿胀、脱嵴。毛细血管扩张,神经纤维中心微管也有水肿。病程6个月:视细胞外节内膜盘断裂溃变,颜色淡,并出现许多泡沫状结构,椭圆体内的线粒体变小,排列不规则,有的脱嵴、水肿,毛细血管已有部分由扩张转为狭窄。结论:糖尿病早期毛细血管由局部扩张转为狭窄,视网膜因缺血、缺氧的加重导致视细胞超微结构的病理改变,并随病程的进展而加重。