The metabolism of galactose cataracts evaluated by phosphorous-31 nuclear magnetic resonance spectroscopy (2)]

The authors evaluated the metabolic kinetics of organophosphate compounds in the course of the evolution of galactose cataracts in rat lenses using phosphorous-31 nuclear magnetic resonance (31P-NMR) spectroscopy. Three-week-old rats (Lewis) were fed with a 25% galactose diet for three days, and one, two, three and four weeks. Metabolic changes in the lenses were measured and the following results were obtained: (1) Changes in glycerophosphorylcholine (GPC) levels over the time course were analogous to changes for choline phosphate (CP); both GPC and CP level showed a significant decrease in the galactose-fed sample compared with the controls from three days after ingestion, and then continued to decrease gradually. This suggested that the decrease of GPC was associated with the level of CP. (2) Inorganic orthophosphate (Pi) increased gradually after the ingestion of galactose, reaching a maximum at third week, and subsequently falling. Adenosine triphosphate (ATP) levels did not show any significant changes at one week, but had fallen significantly at two weeks. There might be metabolic pathways for production of ATP without requirement of Pi in the lens for at least the first one week. (3) Adenosine diphosphate (ADP) levels did not show any significant changes at three days, but had fallen significantly at one week. Nucleotide sugar (NS) increased gradually after the ingestion of galactose, reaching a maximum at second week, and then decreasing. This suggested that the ADP was converted to ADP sugar.     

Influence of galactose cataract on erythrocytic and lenticular glutathione metabolism in albino rats

Context:

Glutathione depletion has been postulated to be the prime reason for galactose cataract. The current research seeks the prospect of targeting erythrocytes to pursue the lens metabolism by studying the glutathione system.

Aims:

To study the activity of the glutathione-linked scavenger enzyme system in the erythrocyte and lens of rats with cataract.

Materials and Methods:

Experiments were conducted in 36 male albino rats weighing 80 ± 20 g of 28 days of age. The rats were divided into two major groups, viz. experimental and control. Six rats in each group were sacrificed every 10 days, for 30 days. Cataract was induced in the experimental group by feeding the rats 30% galactose (w/w). The involvement of reduced glutathione (GSH) and the linked enzymes was studied in the erythrocytes and lens of cataractous as well as control rats.

Statistical Analysis:

Parametric tests like one-way ANOVA and Student''s ‘t’ test were used for comparison. Correlation linear plot was used to compare the erythrocyte and lens metabolism.

Results:

Theconcentration of GSH and the activity of linked enzymes were found decreased with the progression of cataract, and also in comparison to the control. The same linear fashion was also observed in the erythrocytes.

Conclusion:

Depletion of GSH was the prime factor for initiating galactose cataract in the rat model. This depletion may in turn result in enzyme inactivation leading to cross-linking of protein and glycation. The correlation analysis specifies that the biochemical mechanism in the erythrocytes and lens is similar in the rat model.     

阿司匹林对半乳糖性白内障抑制作用的实验研究

目的观察阿司匹林对大鼠半乳糖性白内障的抑制作用。方法将60只Wistar大鼠分为3组：半乳糖组每日腹腔注射80%的D-半乳糖（20mL/kg）,连续10d,制成白内障动物模型;阿司匹林组同半乳糖组处理的同时每日给予阿司匹林混悬液150mg/kg灌胃至实验结束;对照组无特殊处理。实验前及造模起第3、6、10、14、20天行裂隙灯显微镜观察晶状体情况并拍照;造模起第5天各组随机处死8只大鼠,右眼晶状体匀浆检测超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-PX）、过氧化氢酶（CAT）的活性,左侧晶状体行扫描电镜观察并定量分析。结果对照组晶状体始终透明,实验第3、6、10、14、20天阿司匹林组白内障的发生率分别为0、25%、41.67%、58.33%、83.33%,大多数为囊泡初期,而半乳糖组第3天白内障发生率达65%,第6天后晶状体均发生混浊,最终发展为成熟期白内障;实验第5天扫描电镜下见对照组组织结构正常,半乳糖组损伤严重,阿司匹林组损伤较轻微;与对照组比较,半乳糖组SOD、GSH-PX、CAT活性明显降低（P〈0.05）,阿司匹林组各酶活性强于半乳糖组（P〈0.05）。结论阿司匹林能增强晶状体中SOD、GSH-PX、CAT的活性,对大鼠半乳糖性白内障有抗氧化作用,从而延缓早期白内障的发生发展。     

牛磺酸对实验性半乳糖性白内障的防治作用

目的 观察牛磺酸对大鼠半乳糖性白内障的防治作用。方法 设置对照组,白内障组,预防组,结膜下注射组,腹腔注射组,点眼组。采用Ｄ－半乳糖诱发白内障,预防组诱发当开始腹腔注射１５％牛磺酸,其它３个给药组从实验第４天开始分别结膜下注射,腹腔注射,双眼点１５％牛磺酸。     

乙酰水杨酸对晶状体水合反应的影响作用

目的 评估乙酰水杨酸（ＡＳＡ）对半乳糖 性人障晶状体水合反应的影响作用。方法 应用激光拉曼光谱分析技术（ＬＲＳ）和晶状体温浊度开矿学记录（ＬＯＰ）分别从分子水平和临床开矿学观察ＡＳＡ对大鼠半乳糖性白内障晶状体水合反应的影响作用。结果 ＡＳＡ可降低半乳糖性白内联晶状体水合反应的程度,集中表现在以蛋白质变性为主导的后期核质混浊阶段。结论 ＡＳＡ从细胞膜水平影响Ｎa＋／Ｋ＋失衡,降低晶状体水合反应的程度     

水蛭滴眼液防治半乳糖白内障的实验研究

目的 探讨水蛭滴眼液对半乳糖白内障的防治作用。方法 用SD大鼠复制半乳糖白内障模型,以水蛭为主要成分,配制成水蛭滴眼液,并以白内停滴眼液为阳性对照药,动态观察并比较两组滴眼液对半乳糖白内障的影响。于实验第10天测定两组晶状体的超氧化物歧化酶(SOD),谷胱甘肽过氧化物酶(GSH-Px),谷胱甘肽(GSH)和可溶性蛋白(SP)的含量。结果 水蛭组较对照组晶状体混浊速度慢,程度也轻。水蛭组SOD,GSH-Px,GSH的含量均显著高于对照组。结论水蛭滴眼液具有较好的延缓和减轻半乳糖白内障的作用,且优于白内停滴眼液。     

裂隙燈圖像分析系統對大鼠半乳糖性白内障的動熊觀察和定量分級

白内障的發生機理和藥物防治研究一直是眼科研究的重要課題之一,隨着白内障手術的成熟和廣泛開展,白内障的發生機理和藥物防治研究顯得尤為重要.目前,白内障研究的動物模型有很多种[1],半乳糖性白内障動物模型是比較成熟、常被人們選用的方法之一,但對其進行詳細的眼科動態觀察和客觀定量分級尚未見報道,有鉴于此,我們利用自行研制的裂隙燈數字圖像分析系統對大鼠半乳糖性白内障進行動態觀察和定量分級,為進一步探討白内障的發生機理和藥物防治研究提供理論依據.1 材料與方法     

Regional analyses of the reversal process in the neonatal galactose cataract

Reversal of the galactose cataract in neonatal rat lenses involves a decrease in lenticular galactitol, a recovery of existing fiber contour and interdigitation, and a production of new fibers. The onset of neonatal cataractogenesis appeared at 7 days when the young were nursed by mothers placed on a 50% galactose diet at the time of delivery. On the 7th day, the mothers were returned to a normal diet and reversal of the neonatal cataract was monitored for the remainder of the nursing period. After 5 days on a normal diet, cataract reversal was incomplete; this is evidenced by an abnormal fiber contour with decreased number of interdigitating processes, the presence of galactitol and decreased lens size. Fiber alterations were most pronounced in the anterior superficial cortex (0–200 μm from the capsule). As the reversal period progressed for an additional 8 days, lenticular galactitol declined and normalization of anterior superficial and supranuclear cortical fibers occurred.Growth of the normal and reversal lenses was compared by determining the number of fiber lamellae produced per day. As new fibers were formed, by the anterior lens epithelium, the radius of the lenses increased with time; the increase in lens radius and the average fiber width were measured for the juvenile lenses (12–63 days) and the reversal lenses (12–20 days). The number of fiber lamellae produced during each growth period was calculated. Normal lens growth was a consistent 1 fiber lamella/day. During the reversal period, lens growth was increased with respect to normal; the source of the rapid generation of new fibers may be the differentiation of equatorial, multilayered epithelial cells which were induced by the galactose feeding.     

Further observations on the effect of galactose on the development of X-ray-induced cataract in mice

The effect of a 30% galactose diet on the progression of X-ray-induced cataract in mice was evaluated by following morphological changes as seen by light and transmission electron microscopy in different regions of the lens. Lens opacities as observed with the slit-lamp biomicroscope developed at a slower rate in galactose-fed animals than in those on a normal diet. The protective effect of galactose on X-ray cataract was seen whether galactose feeding was initiated either 1 week before or after exposure to X-ray. At 4 months after X-ray approximately 50% of galactose-fed animals had mature cataracts, compared to 100% in the control group. Similarly, at two weeks after exposure to X-ray, before any lens opacities were observed, morphological changes were more severe in the control group; cells in the meridional row were more disorganized in the control than in the galactose-fed groups. However, the progression of mature cataracts in the two galactose-fed groups were not significantly different. Since free radicals produced by X-ray are thought to be short-lived, the protective effect of galactose feeding after X-ray was unexpected, raising the possibility that some of the active species may be long-lasting. The nature of such radicals, if any, is unknown and remains to be investigated.     

Effect of sodium iodate injection on the development of galactose cataract in the rat

The effect of sodium iodate injection on the development of galactose cataract in the rat was investigated clinically and biochemically. Galactose cataracts were induced in animals which had been injected with a single dose of sodium iodate and compared with those given a saline injection. The degeneration of retinal pigment epithelium was observed electron microscopically after sodium iodate injection. A slit lamp examination of the lens showed that, in animals injected with sodium iodate, galactose-associated lens alterations progressed faster, and mature cataract development was achieved earlier than in the saline-injected animals. Biochemical data which indicated a significantly higher concentration of Na+ and lower concentration of K+ in lenses of sodium iodate-injected animals confirmed the above clinical data. The level of galactitol was higher in lenses of sodium iodate-injected than those of saline-injected animals. Acceleration of the development of galactose cataract following sodium iodate injection is apparently due to the higher level of galactose entering the aqueous humor because of breakdown of blood-ocular barriers.     

维拉帕米在控制半乳糖性白内障中的作用

目的 观察维拉帕为（ｖｅｒａｐａｍｉｌ）在半乳糖性白内障形成和发展过程中的作用。方法 ５５只Ｗｉｓｔａｒ在雄性大鼠分为４组,２组动物每日腹腔注射５０％Ｄ－半乳糖两次,剂量为３０ｍｌ／（ｋｇ．ｄ）,其中１组每天皮下注射维拉帕米１２ｍｇ／（ｋｇ．ｄ）,共３０天。另２组注射相同剂量的生理盐水,其中１组动物也给予皮下注射维拉帕米,观察时间相同。术后不同时间散瞳观察晶状体的动态变化,用日本岛津ＡＡ－６４０－     

半乳糖性大鼠白内障晶体内前列腺素生物合成的研究

对半乳糖性白内障晶体内微粒体生物合成前列腺素能力变化分析发现：用５０％半乳糖喂养２４小时后晶体内ＰＧＦ２α水平降至对照组的３１．１１％；４８小时后为对照组的５８．０４％，第５天时为对照组的５２．１９％，在第九天时为对照组的４８．０２％，第２１天时为对照组的３２．１５％，研究发现半乳糖性白内障晶体内前列腺素合成能力受到明显影响，而这可能与白内障形成有关。     

大鼠半乳糖性白内障模型的表现和病理特征

背景建立稳定的糖尿病性白内障动物模型是研究白内障发病机制和药物治疗的前提。目前半乳糖性白内障模型已被广泛用于相关的研究,但不同的给糖方式会导致白内障出现的时间、程度及形态的差异。目的探讨半乳糖性白内障的眼部表现和病理特征。方法56只sD大鼠按随机数字表法随机分为模型组和对照组,每组28只。模型组大鼠用质量分数50％D－半乳糖饲料喂养SD大鼠共30d,对照组大鼠给予普通饲料喂养。喂养期间隔日在裂隙灯显微镜下观察晶状体的混浊部位及其形态,并对Suryanarayana提出的晶状体混浊的分级标准进行改良。于半乳糖喂养后的第5、10、15、20、25和30天分别观察大鼠的体质量变化,上述各时间点分别获取大鼠的晶状体并制作样本切片,行苏木精一伊红染色,检测晶状体的组织病理学改变。此外分别测量晶状体的湿质量和干质量,评估晶状体内水含量的变化特点。结果实验后10～30d,模型组大鼠的体质量较对照组均明显下降,差异均有统计学意义（P〈0．05）。在喂养半乳糖的过程中,随着时间的延长,模型组大鼠晶状体均发生不同级别的皮质和核的混浊,而对照组大鼠晶状体始终透明。裂隙灯下和晶状体的组织病理学检查均表明晶状体的混浊起始于赤道部皮质纤维,逐渐向中心区皮质扩展,随后晶状体核逐渐混浊、膨胀。组织学检查示晶状体皮质纤维水肿,晶状体上皮细胞分化、脱核延迟。实验第30天,模型组大鼠晶状体的湿质量明显高于对照组,差异有统计学意义（t=138．571,P〈O．05）;模型组大鼠晶状体的干质量明显低于对照组,差异有统计学意义（t=－52．468,P〈0．05）,实验过程中模型组大鼠晶状体干湿质量比明显下降,而对照组无明显变化,各时间点2组间的差异均有统计学意义（P〈0.05）。结论大鼠半乳糖性白内障模型的病程与人年龄相关性皮质性白内障的自然病程和发病机制相似。喂养50％D－半乳糖饲料造模的方法具有成模时间适中、临床分期特征明确等特点,是一种较理想的研究白内障发病机制和药物防治的模型。