褪黑素对糖尿病视网膜病变防治作用的研究进展

大量的研究已经证实,氧化应激在糖尿病视网膜病变(DR)的发生中起主导作用.褪黑素(MLT)是体内很强的抗氧化剂之一,它可以直接清除体内自由基,或通过提高抗氧化酶的活性促进自由基的清除;MLT易于透过血-脑屏障抑制神经胶质细胞的反应性增生,防止视网膜神经组织的氧化损伤;MLT通过抑制诱导型一氧化氮合酶的表达,起到保护视网膜血管内皮细胞的作用;并具有调节血糖水平等作用.MLT针对DR的病因,从多方面起到防治DR的作用,有望成为主要的治疗药物.就近年来MLT对DR防治作用的研究进展做一综述.     

氧化损伤在青光眼发病中的作用

青光眼是一种多因素诱导的视神经退行性病变,其中氧化应激损伤在复杂的青光眼发病机制中的起着重要作用.青光眼的氧化损伤机制可能对眼部的某些组织细胞产生损伤作用,促使细胞内抗氧化物酶作用下降、抗氧化作用相关蛋白增加,最终导致蛋白沉积、细胞死亡.氧化损伤可以导致小梁网细胞线粒体骨架改变,最终使小梁网发生退行性病理改变.氧化损伤还可促使视网膜神经节细胞内抗氧化作用相关蛋白增加、线粒体内源性凋亡,最终导致视网膜神经节细胞功能丧失.     

异补骨脂素对氧化损伤的人晶状体上皮细胞的防护作用及其机制

白内障是世界范围内最主要的致盲性眼病.晶状体氧化损伤导致白内障,晶状体可依靠一系列抗氧化系统保护其免受氧化损伤.抗氧化系统中,有酶性抗氧化物和非酶性抗氧化物.     

异补骨脂素对氧化损伤的人晶状体上皮细胞的防护作用及其机制

白内障是世界范围内最主要的致盲性眼病.晶状体氧化损伤导致白内障,晶状体可依靠一系列抗氧化系统保护其免受氧化损伤.抗氧化系统中,有酶性抗氧化物和非酶性抗氧化物.     

异补骨脂素对氧化损伤的人晶状体上皮细胞的防护作用及其机制

白内障是世界范围内最主要的致盲性眼病.晶状体氧化损伤导致白内障,晶状体可依靠一系列抗氧化系统保护其免受氧化损伤.抗氧化系统中,有酶性抗氧化物和非酶性抗氧化物.     

高级糖基化终末产物与糖尿病视网膜病变的关系

高级糖基化终末产物(advanced glycation end products,AGE)的堆积是糖尿病视网膜病变(diabetic retinopathy,DR)主要的致病因素,其可促进视网膜色素上皮(retinal pigment epithelium,RPE)细胞AGE受体(receptor of AGE,RAGE)的表达、血管内皮生长因子(vascular endothelial growth factor,VEGF)的分泌及细胞凋亡损伤.RPE细胞参与构成视网膜的外屏障,具有屏障、滤过、吞噬和分泌等作用,在维持视网膜正常生理功能方面具有重要作用,RPE细胞的功能损害会导致多种视网膜疾病.通过研究AGE对RPE细胞的损伤,探讨AGE在DR发生发展中的作用,有利于寻找有效防治DR的新途径.     

Nrf2通路在糖尿病视网膜病变中的研究进展

糖尿病视网膜病变(DR)作为糖尿病的一种严重并发症,可能导致严重的视力下降或丧失.核因子E2相关因子2(Nrf2)是一种在氧化应激及炎症相关组织损伤中发挥重要作用的氧化还原敏感转录因子.越来越多的研究表明,Nrf2在DR的发生和发展中起着重要作用.本文就Nrf2通路在糖尿病、DR发病中的作用及其与血管内皮生长因子(VEGF)表达的相关性进行综述.     

M2型丙酮酸激酶在糖尿病视网膜病变中的作用

糖尿病视网膜病变(DR)是一种糖尿病中最常见的高度特异性微血管并发症,是全球20~65岁人群视力障碍和失明的主要原因,主要表现为视网膜内微血管的异常及新生血管的形成。糖酵解过程是从葡萄糖分解开始到丙酮酸生成的过程,可以为机体迅速提供能量,内皮细胞多数通过糖酵解产生的ATP来维持其功能,包括维持紧密连接和屏障作用。丙酮酸激酶(PK)的M2亚型(PKM2)作为糖酵解的关键酶,在机体的大多数组织中均有表达。内皮细胞和光感受器细胞作为视网膜中的重要细胞成分,在DR的发生发展过程中发挥重要作用。研究表明,PKM2通过代谢和非代谢方式调节内皮细胞和光感受器的功能,在DR发展中发挥重要作用。因此,本文将重点通过内皮细胞和光感受器细胞两个方面来综述PKM2在糖尿病视网膜病变中的研究进展,从而为DR的诊断和治疗提供新思路。     

糖尿病性视网膜病变发病机制研究进展

糖尿病性视网膜病变（DR）是糖尿病最常见和最严重的微血管并发症之一,DR的病理特征为视网膜新生血管形成和BRB破坏,它是糖尿病患者视力丧失的主要原因。高血糖是糖尿病并发症发生和发展的重要危险因素,而糖尿病最终如何导致DR发病的机制十分复杂。长期的高血糖症导致氧化酶损伤,微血栓形成,细胞粘附分子活化,白细胞郁积和细胞因子活化,继之,缺氧调节的生长因子的表达增加和细胞因子的产生。在这个机制中起主要作用的因子为VEGF、IGF-1、TNF-α、IL-1β、FGF等。多种因子相互作用引起视网膜新生血管形成和血—视网膜屏障（BRB）破坏在DR的发生和发展中起着关键作用。本文通过文献回顾,综述了糖尿病性视网膜病变发病机制的研究进展。     

线粒体功能障碍及氧化应激与糖尿病视网膜病变关系的研究

糖尿病视网膜病变(diabetic retinopathy,DR)为糖尿病的严重并发症之一,已成为致盲的主要眼疾。DR的发生发展与多种因素有关,发病机制复杂,尚不明确,早期的资料表明,其发生发展与血糖水平、糖尿病病程、环境等多种因素相关。其中线粒体功能障碍和氧化应激反应是导致DR发生的重要机制之一,已成为近几年的研究热点。细胞内线粒体功能障碍的后果包括因为线粒体活性氧(ROS)的产生率升高而导致的电子传递链蛋白的损伤,以及线粒体DNA(mt DNA)的损害和代谢能力的降低。明确把握高糖下线粒体的功能变化和氧化应激反应在DR发生发展过程中的作用机制,对DR的防治具有重要意义。因此本文就相关研究发展做一综述。     

Role of oxidative stress,inflammation, hypoxia and angiogenesis in the development of diabetic retinopathy

Diabetic retinopathy (DR) is a retinal disease which is one of the most severe complications occuring due to diabetes mellitus and is a major cause of blindness. Patients who have diabetes mellitus for number of years develop characteristic group of lesions in the retina which leads to Diabetic retinopathy. It is a multifactorial condition occuring due to complex cellular interactions between biochemical and metabolic abnormalities taking place in all retinal cells. Considerable research efforts in the past 20?years have suggested that the microvasculature of the retina responds to hyperglycemia through a number of biochemical changes, which includes polyol pathway, protein kinase C activation, upregulation of advanced glycation end products formation and renin angiotensin system activation. Various previous studies had suggest that interaction of these biochemical changes may cause a cascade of events, such as apoptosis, oxidative stress, inflammation and angiogenesis which can lead to the damage of a diabetic retina, causing DR. This highlights that oxidative stress, inflammation, angiogenesis-related factors triggers the occurrence of retinal complication in diabetes are highlighted.     

氧化应激与糖尿病视网膜病变的研究进展

糖尿病视网膜病变（ｄｉａｂｅｔｉｃｒｅｔｉｎｏｐａｔｈｙ,ＤＲ）是糖尿病常见且严重的微血管并发症之一。ＤＲ的发生与多种因素相关,其发病机制至今尚未完全阐明。近年来,人们越来越重视氧化应激和抗氧化治疗对ＤＲ的作用。了解氧化应激与ＤＲ的关系将有助于ＤＲ治疗手段的更新。本文就有关氧化应激与ＤＲ的研究进展作一综述。     

一氧化氮和一氧化氮合酶基因多态性与糖尿病视网膜病变

糖尿病视网膜病变(diabetic retinopathy,DR)是重要致盲性眼病之一,其发生和进展与血糖水平、疾病病程、环境及遗传等多种因素有关。一氧化氮(NO)作为一种重要的血管活性物质,与DR中毛细血管闭塞、微循环障碍、内皮细胞增殖相关。一氧化氮合成酶(NOS)是NO合成过程中的关键酶,我们就NO和NOS基因多态性与DR的关系进行综述。     

Association between endoplasmic reticulum stress and risk factors of diabetic retinopathy

Diabetic retinopathy (DR) is one of the most common and challenging ocular complications of diabetes mellitus. As a chronic, progressive ocular disease that poses a serious threat to vision, DR has gradually become a leading cause of blindness worldwide. Emerging evidence points to an important role of endoplasmic reticulum (ER) stress in not only maintaining the steady-state equilibrium in the body, but also in intracellular synthesis, protein folding, and other essential functions. Recent studies have demonstrated clear associations between ER stress-related physiological functions and the pathogenesis of DR. When cells are stimulated by external stimuli, UPR pathway is activated firstly to protect it. However, long-term harmful factors can induce ER stress. which interferes with the physiological metabolism of retinal cells and participates in the occurrence of DR via the ATF6 pathway, PERK pathway and IRE1 pathway. At present, ER stress blocker is expected to become a new anti-DR therapy. Thus, understanding the relationship between ER stress and DR will help to develop new effective preventative treatments. In this review, we summarize the risk factors of DR pathogenesis induced by ER stress toward revealing potentially new therapeutic targets.     

中药单体治疗糖尿病视网膜病变的研究进展

糖尿病视网膜病变(DR)是一种常见的糖尿病慢性并发症,可导致视网膜中微血管的不可逆性损伤,是糖尿病患者首要致盲性眼病。DR的发病机制主要涉及氧化应激、炎症反应与新生血管形成等因素。临床上多以视网膜激光光凝术、玻璃体切割术或药物治疗为主。我国传统中药组方与中药单体在DR治疗,特别是视网膜保护方面具有独特功效,为DR治疗提供有益补充。本文综述了代表性中药组方与中药单体在DR治疗中的应用实践与作用机制,以期为DR的临床治疗与新药研发提供参考。     

The effect of up- and downregulation of MnSOD enzyme on oxidative stress in human lens epithelial cells

PURPOSE: Gene knockouts serve as useful experimental models to investigate the role of antioxidant enzymes in protection against oxidative stress in the lens. In the absence of gene knockout animals for Mn-containing superoxide dismutase (MnSOD), the effect of this enzyme on oxidative stress was investigated in a human lens epithelial cell line (SRA 01/04) in which the enzyme was up- or downregulated by transfection with sense and antisense expression vectors for MnSOD. METHODS: Human lens epithelial cells (SRA 01/04) were transfected with plasmids containing sense and antisense human cDNA for MnSOD. The enzyme levels were determined by Western blot analysis and immunocytochemistry. The protective effect of the enzyme against the cytotoxicity of H(2)O(2) was evaluated by cell viability, DNA strand breaks, and morphologic changes observed by transmission electron microscopy. In addition, the protective effect of this enzyme against photochemically induced stress and UVB irradiation in cells was assessed by measuring the damage of cellular DNA. RESULTS: The MnSOD level in upregulated cells was three times higher than in downregulated cells, and the enzyme surrounded the nucleus. Cells with elevated enzyme levels were more resistant to the cytotoxic effect of H(2)O(2) with greater cell viability. MnSOD-deficient cells showed dramatic mitochondrial damage when exposed to 50 micro M H(2)O(2) for 1 hour. Similarly, oxidative challenge by H(2)O(2), photochemically generated reactive oxygen species, or UVB irradiation produced greater DNA strand breaks in MnSOD-deficient cells than in those in which the enzyme was upregulated. CONCLUSIONS: These findings demonstrate the protective effect of MnSOD in antioxidant defense of cultured lens epithelial cells. This approach to modulating the enzyme level in cultured cells provides a new experimental model for study of the role of antioxidant enzymes in the lens.     

葡萄籽原花青素调控NLRP3/Caspase-1通路介导的焦亡途径对糖尿病视网膜病变大鼠的保护作用

目的　探讨葡萄籽原花青素调控NLRP3/Caspase-1通路介导的焦亡途径对糖尿病视网膜病变（DR）大鼠的保护作用。方法　建立DR大鼠模型，随机分为模型组、葡萄籽原花青素组、VX-765组、葡萄籽原花青素+VX-765组（每组各12只），另取12只大鼠为对照组，药物干预14 d，HE染色观察各组大鼠视网膜组织病理学变化；TUNEL染色检测各组大鼠视网膜神经节细胞（RGC）焦亡情况；采用试剂盒测定各组大鼠视网膜组织超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、活性氧（ROS）、丙二醛（MDA）及血清中炎症因子糖基化终末产物（AGEs）、白细胞介素（IL）-1β与IL-18水平；Western blot检测各组大鼠视网膜组织NLRP3/Caspase-1通路蛋白表达水平。结果　与对照组相比，模型组大鼠视网膜组织明显变薄，结构疏松，细胞结构层次紊乱、排列不规则，RGC变少、稀疏，呈现严重病理损伤变化，RGC焦亡率，ROS与MDA水平，AGEs、IL-1β、IL-18水平，NLRP3与Caspase-1蛋白表达水平均显著升高（均为P<0.05），SOD与CAT水平均显著降低（均为P<0.05）。与模型组相比，葡萄籽原花青素组、VX-765组大鼠视网膜组织形态结构得到恢复，病理损伤均有不同程度减轻，RGC焦亡率，ROS与MDA水平，AGEs、IL-1β与IL-18水平，NLRP3与Caspase-1蛋白表达水平均降低（均为P<0.05），SOD与CAT水平均升高（均为P<0.05）。与葡萄籽原花青素组及VX-765组分别相比，葡萄籽原花青素+VX-765组大鼠视网膜组织病理损伤进一步减轻，形态结构几乎恢复正常，RGC焦亡率，ROS与MDA水平，AGEs、IL-1β与IL-18水平，NLRP3与Caspase-1蛋白表达水平均降低（均为P<0.05），SOD与CAT水平均升高（均为P<0.05）。结论　葡萄籽原花青素可以抑制炎症发生发展，增强DR大鼠抗氧化活性，减轻过氧化反应，缓解视网膜组织病理学损伤，减少RGC焦亡，可能是通过抑制NLRP3/Caspase-1信号通路实现的。     

The effect of L-carnitine in the prevention of ionizing radiation-induced cataracts: a rat model

Background The objective was to determine the antioxidant role of L-carnitine (LC) against ionizing radiation-induced cataracts in lens after total cranium irradiation of rats with a single dose of 5 Gy. Methods Sprague-Dawley rats were used in this experiment and were divided into three groups. Group 1 did not receive LC or irradiation (control group). Group 2 received a 5 Gy gamma irradiation as a single dose to the total cranium (RT group). Group 3 received total cranium irradiation plus 100 mg/kg body weight/day LC (RT+LC group). The rats were irradiated using a cobalt-60 teletherapy unit. At the end of the 10th day, the rats were sacrificed and their eyes were enucleated. The lenticular activity of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured. Furthermore, the lenticular content of an indicator of lipid peroxidation, malondialdehyde (MDA), was measured. Results Irradiation significantly increased the MDA level as an end product of lipid peroxidation. Irradiation also significantly decreased SOD activity and increased GSH-Px activity, indicating the generation of oxidative stress and an early protective response to oxidative damage. Irradiation with 5 Gy to the total cranium as a single fraction formed cataracts in the rat lenses. Cataract development was detectable in 9 rats in the RT group, and in only 4 rats in the RT+LC group 10 days after irradiation. LC administration plus irradiation significantly decreased the MDA level and increased the activity of SOD and GSH-Px enzymes, which might indicate the protection of the lenses from gamma radiation-induced cataracts. Conclusions L-carnitine may protect against the damage produced by gamma radiation by increasing the activity of the SOD enzyme and by scavenging free radicals generated by ionizing radiation. As a result of this process, MDA as an indicator of lipid peroxidation may decrease.