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。     

蚕蛹油对D-半乳糖模型小鼠学习记忆及氧化应激的影响

目的：观察蚕蛹油对D-半乳糖致衰老小鼠学习记忆能力及机体抗氧化能力的影响,为蚕蛹油的临床应用积累资料。 方法：连续给小鼠腹腔注射D-半乳糖30 天,同时用蚕蛹油灌胃给药,给药结束后用Morris水迷宫进行4天的定位航行试验,测定逃避潜伏期;第5天进行空间搜索试验,测定其穿越平台次数;并比较了各组小鼠组织中超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-PX）活性和丙二醛（MDA）含量。 结果：与模型组比较,蚕蛹油6 ml/kg·d组逃避潜伏期明显短于模型组（P<0.05）;蚕蛹油6 ml/kg·d组与12 ml/kg·d组穿越平台次数明显多于模型组（P<0.05）;蚕蛹油12 ml/kg·d组能显著提高D-半乳糖所致衰老小鼠脑组织SOD、GSH-PX活性,降低脂质过氧化产物MDA的含量。 结论：蚕蛹油能改善D-半乳糖致衰老小鼠的学习记忆能力,有抑制其脑组织脂质过氧化的作用。     

Effect of sodium concentration and plasma sugar concentration on hexose absorption by the rat jejunum in vivo

The sodium-dependency of both the saturable and non-saturable components of glucose and galactose absorption across the rat jejunum in vivo has been determined. The non-saturable process appears to be unaffected by sodium removal but when Na⁺ concentrations in the lumenal fluid are progressively reduced from 143 mM to 0 mM theJ _max for active absorption is greatly decreased.In a separate study these two components of glucose transport were further investigated using intravenous sugar infusion to modify the transepithelial sugar concentration gradient. When identical glucose concentrations were present in plasma and intestinal lumen, the reduction in glucose absorption was fully accounted for by the elimination of the non-saturable component from the overall absorptive process. Together, these observations can be interpreted as further evidence for the existence of at least two absorption processes in vivo. The implication for analysing results from experimental studies of intestinal sugar absorption in vivo is discussed.     

A PATIENT WITH HEREDITARY GALACTOSEMIA STUDIED WITH A SCREENING METHOD FOR GALACTOSE IN URINE

A case of hereditary galactosemia in a newborn infant is reported. Dietary treatment was started on the 9th day of life, which caused a dramatical improvement in the patient's condition. Diagnosis was confirmed by assay of galactose in urine and blood, and finally by demonstration of the enzyme deficiency in the red blood cells of the patient. Both parents had low values for galactose-1-phosphate uridyl transferase activity in red blood cells, in agreement with the fact that they are heterozygotes for hereditary galactosemia. A recently described test paper for galactose in urine was used both in the diagnosis of the disease and for the control of the suitability of the patient's diet. In addition to galactose, the urine also contained large anounts of galactitol. On the introduction of galactose-free diet, galactitol dis-appeared from the urine more slowly than did galactose. There was an increased concentration of amino acids in the blood and in the urine, as a result of liver damage and also decreased tubular reabsorption. Also the aminoaciduria and the increased blood amino acid concentration disappeared on galactose-free diet.     

2-deoxy-2-[18F]fluoro-d-galactose: A new tracer for the measurement of galactose metabolism in the liver by position emission tomography

We prepared 2-deoxy-2-[¹⁸F]fluoro-d-galactose as a potential radiopharmaceutical for liver imaging and for the assessement by position emission tomography of regional metabolic function of the liver. In biodistribution studies of rats, the liver uptake of the compound was very high, almost reaching a plateau (6.33% dose/g) at 30 min and remaining constant until 120 min. This high uptake was reduced by simultaneous administration of d-galactose, but d-glucose had no effect. The compound was much less concentrated in the liver that had been damaged by CCl₄ treatment. Positron imaging of a rabbit liver showed a remarkable uptake of the compound with a high liver-to-blood ratio. The high concentration in the liver was also reduced by the administration of d-galactose. These data suggest that the compound was trapped in the liver by a metabolic process and could be used for the measurement by position emission tomography of galactose metabolism in the liver.     

Histochemical studies on alkaline phosphatases in mineralizing oral tissues in the mouse

The effect of galactose on bone metabolism was studied by feeding young rats a semisynthetic diet containing 35% of this monosaccharide. Control animals received the same diet without galactose but with glucose. Both a low, and a normal, Ca–P intake were studied in the control and galactose fed groups. Bone glucose-6-phosphate dehydrogenase was inhibited as galactose accumulated in the tissue. Urinary excretion of calcium, pyrophosphate, aminopolysaccharides, hydroxyproline and plasma alkaline phosphatase (bone isoenzyme) were significantly increased above control levels. Galactose fed animals on a low Ca and P diet showed a negative Ca balance, primarily due to a fecal excretion which was greater than intake. An inverse relationship between calcium balance and food intake was observed. The adverse effect of galactose on calcium metabolism may be mediated by an effect on bone cells and on renal and intestinal function, related perhaps to an as yet non-defined disturbance of carbohydrate metabolism.

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Zusammenfassung Die Wirkung von Galaktose auf den Knochenstoffwechsel junger Ratten wurde untersucht, indem diese eine semisynthetische Nahrung erhielten, welche 35% dieses Monosaccharids enthielt. Kontrolltiere erhielten dieselbe Nahrung ohne Galaktose, aber mit Glukose. Die Kontrollgruppe und die Gruppe mit Galaktosenahrung erhielten eine niedrige und eine normal Ca–P-Einnahme. Die Glukose-6-Phosphat-Dehydrogenase des Knochens wurde gehemmt, wenn Galaktose im Gewebe zunahm. Die Urinausscheidung von Calcium, Pyrophosphat, Aminopolysacchariden, Hydroxyprolin und alkalischer Phosphatase des Plasmas (Knochen-Isoenzym) war signifikant höher als bei den Kontrollen. Die Tiere mit Galaktosezusatz und niedriger Ca–P-Aufnahme zeigten eine negative Calciumbilanz, die hauptsächlich durch eine fäkale Ausscheidung bedingt war, welche höher war als die Einnahme. Es wurde eine umgekehrt proportionale Beziehung zwischen Calciumbilanz und Nahrungseinnahme beobachtet. Die nachteilige Wirkung von Galaktose auf den Calciumstoffwechsel mag von einer Wirkung auf die Knochenzellen und auf die Nieren- und Darmfunktion herrühren, vielleicht im Zusammenhang mit einer noch unbestimmten Störung des Kohlenhydratstoffwechsels.

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Résumé L'effet du galactose sur le métabolisme osseux est étudié en soumettant de jeunes rats à un régime semi-synthétique contenant 35% de ce monosaccharide. Les animaux témoins reçoivent le même régime sans galactose, avec du glucose. L'effet d'une consommation de Ca–P, normal et faible, est étudié chez les témoins et les groupes soumis au galactose. La glucose-6-phosphate deshydrogénase osseuse est inhibée lorsque le galactose s'accumule dans les tissues. L'excrétion urinaire de calcium, pyrophosphate, aminopolysaccharides, hydroxyproline en phosphatase alcaline plasmatique (isoenzyme osseuse) est augmentée de façon significative par rapport aux témoins. Les animaux, recevant du galactose avec un régime faible en Ca et P, présentent une balance négative en Ca, due surtout à un excretion fécale plus élevée que les apports. Un rapport inverse est observé entre la balance calcique et l'ingestion alimentaire. L'effet nocif du galactose sur le métabolisme du calcium pourrait agir par l'intermédiaire d'une action sur les cellules osseuses et les fonctions rénales et intestinales, en rapport, peut-être, avec un trouble inconnu du métabolisme hydro-carboné.

     

大鼠内耳拟老化模型对卡那霉素耳毒性的易感性

目的 研究大鼠内耳拟老化模型对卡那霉素的易感性.方法 Wistar大鼠50只,随机分为4组,A组(半乳糖组,14只)5%D-半乳糖颈部皮下注射(150 mg·kg-1·d-1),共8周,继以生理盐水腹腔注射10 d;B组(半乳糖加卡那霉素组,14只)皮下注射半乳糖同A组,8周后,腹腔注射硫酸卡那霉素(500 mg·kg-1·d-1)10 d;C组(卡那霉素组,12只)前8周用生理盐水代替半乳糖,后10 d注射卡那霉素同B组;D组(空白对照组,10只)仅给予生理盐水注射.听性脑干反应(auditory brainstem respones,ABR)检测各组大鼠反应阈,比色法检测各组大鼠膜迷路谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-PX)活性.利用巢式聚合酶链式反应技术检测内耳组织线粒体DNA4834 bp缺失突变的发生情况.结果 用药后A组大鼠线粒体DNA 4834 bp缺失突变发生率为100%(28耳/28耳),B组为92.86%(26 耳/28耳),C组和D组均无线粒体DNA 4834 bp缺失突变检出.A组GSH-PX活性为(59.07±8.70)U(-x±s,下同),B组(63.29±12.40)U,C组(136.67±9.53)U,D组(142.10±7.02)U;A组和D组之间差异具有统计学意义(P=0.000),A组和B组、C组和D组之间差异无统计学意义(P值分别为0.307和0.151).ABR阈值(峰值等效声压级)A组平均提高(5.36±3.08)dB,B组为(61.79±11.20)dB,C组为(34.17±4.69)dB,D组为(6.50±3.37)dB;A组和D组之间差异无统计学意义(P=0.398),B组和D组、B组和C组、C组和D组之间差异具有统计学意义(P值均为0.000).结论 D-半乳糖可以诱导大鼠内耳拟老化模型,内耳组织中线粒体DNA 4834 bp缺失突变率极高,该模型对卡那霉素耳毒性的易感性增强.     

Exposure to Topical Bovine Thrombin During Surgery Elicits a Response Against the Xenogeneic Carbohydrate Galactose α1-3Galactose

Exposure of humans to topical bovine thrombin has been associated with development of antibodies against bovine and human coagulation factors and blood coagulation abnormalities. However, the nature of this humoral response is unknown. In this study, numerous glycoproteins in the topical bovine thrombin were found to contain the Gal1-3Gal epitope, which is known to be highly immunogenic. More importantly, Gal1-3Gal is recognized by natural antibodies that are found in all normal individuals and are known to effectively mediate complement activation and subsequent destruction of xenogeneic tissues. Thus, primary exposure of normal individuals to topical bovine thrombin is expected to result in an immediate immune reaction against that reagent. Further, following exposure to topical bovine thrombin, the levels of anti-Gal1-3Gal IgG rose to levels tenfold greater than the average level of natural anti-Gal1-3Gal IgG in naive individuals. Thus, Gal1-3Gal in topical bovine thrombin accounts for, at least in part, the highly immunogenic nature of this reagent.     

半乳糖氧化酶法检测直肠粘液T－抗原

为建立一种用于大肠癌早期筛检的指标，采用半乳糖氧化酶法检测了２４６例直肠粘液标本中的Ｔ抗原。其中３５例大肠癌患者的阳性检出率为８２．８％；８６例大肠息肉患者中肿瘤性息肉阳性率为４９．０％，炎性息肉阳性率为１４．２％；在７３例肠道慢性炎症患者中阳性率为１６．４％；在５０例大肠粘膜正常的患者中阳性率为８．０％。结果表明，用半乳糖氧化酶法检测Ｔ抗原对大肠癌的筛检具有较高的敏感性（８２．８％）和特异性（９２．０％），方法简便，重复性好，并且，也为大肠息肉的筛检及其恶变的监测提供了一种可供选择的方法。