丙烯腈亚急性中毒对大鼠肝脏的影响

本研究以灌胃染毒的方法,通过光镜、电镜观察和酶组化及血清生化指标测定,探讨了丙烯腈对大鼠肝脏的亚急性毒作用。结果表明,丙烯腈能引起肝细胞线粒体、粗面内质网及生物膜功能障碍和结构损伤。     

D-半乳糖衰老大鼠下颌下腺超微结构的改变

目的探讨实验性衰老大鼠下颌下腺超微结构的改变。方法用D-半乳糖制造衰老大鼠模型。2组大鼠经4%多聚甲醛＋2.5%戊二醛灌注固定,常规方法制备下颌下腺超薄切片,透射电镜下观察主要细胞的超微结构。结果正常组大鼠颗粒曲管（GCT）及腺细胞内粗面内质网、线粒体、高尔基复合体发达,粗面内质网网腔均匀、表面附有较多核糖体颗粒;核膜清晰,染色质分布均匀,可见丰富的质膜内褶。模型组GCT及腺细胞核固缩,染色质浓缩,部分细胞膜断裂,可见线粒体肿胀及嵴断裂,粗面内质网减少、有核糖体脱落现象。结论D-半乳糖模型大鼠下颌下腺超微结构发生明显衰老改变。     

氰戊菊酯染毒大鼠肺泡巨噬细胞超微结构的定量分析

根据立体学原理和方法,对染毒氰戊菊酯大鼠肺泡巨噬细胞超微结构改变进行了定量分析。主要结构参数包括细胞核、细胞浆、线粒体、溶酶体、高尔基体、粗面和滑面内质网以及脂滴的体密度,脂滴、溶酶体、线粒体外膜的面密度和数密度。绝大多数参数呈现明显的剂量依赖关系和时间反应特征。     

清肺口服液含药血清对呼吸道合胞病毒感染细胞超微结构改变影响的实验研究

目的观察清肺口服液含药血清对呼吸道合胞病毒（RSV）感染后细胞超微结构改变的影响。方法制备清肺口服液含药血清,应用细胞培养技术,将培养的人胚肺成纤维细胞（Hep-2）分组,利用电镜观察呼吸道合胞病毒攻击后各组人胚肺成纤维细胞超微结构的变化。结果病毒攻击组细胞核增大,核质比增加,核仁凝聚,核膜凹陷成夹层,包涵体形成,线粒体凝聚,粗面内质网扩张,溶酶体增多,核染色质浓缩,细胞外可见病毒颗粒。含药血清感染时给药组细胞核大小基本正常,有的轻度增大,无核仁凝聚,无包涵体形成,粗面内质网形态正常,线粒体基本正常,偶有凝聚现象,细胞间很少找到病毒颗粒。含药血清感染后给药组细胞核增大,核仁凝聚,粗面内质网扩张,线粒体凝聚,但程度较轻。结论RSV感染人胚肺成纤维细胞后,细胞可出现超微结构的改变,清肺口服液含药血清可以减轻这种改变。感染时给药比感染后给药作用更明显。     

3-硝基丙酸对沙土鼠海马CA1区锥体细胞超微结构的影响

目的观察小剂量3-硝基丙酸(≤20mg/kg)对沙土鼠海马CA1区锥体细胞超微结构的影响.方法将沙土鼠腹腔注射不同剂量3-硝基丙酸或双蒸水后3d,取海马CA1 区用戊二醛和锇酸固定,电镜下观察CA1区锥体细胞层神经元细胞核和细胞器超微结构形态变化,用体视学方法计算每张照片线粒体和粗面内质网体面积变化.结果实验组与对照组比较细胞核无明显变化,线粒体和粗面内质网轻度肿胀,体密度高于对照组.结论小剂量3-硝基丙酸可引起神经元缺氧代偿性反应,无致死性损害.     

二氧化碳激光辐射损伤区水肿外带的超微病理研究

CO_2激光对神经组织的辐射损伤光镜下分为碳化带、凝固带和水肿带。我所在电镜下发现在水肿带外层仍有神经组织的輻射损伤,主要表现为细胞的线粒体、粗面内质网、高尔基复合体、突触等细胞器肿胀,变性的移行性病理改变。我们将这一病变区命名为“水肿外带”。     

线粒体及内质网对铅引起的[Ca2+]i升高的作用

目的 研究线粒体、内质网Ca^2 -ATP酶以及Na^ 和K^ -ATP酶活力的改变对铅引起的[Ca^2 ]i升高的调节作用，探讨铅引起的[Ca^2 ]i增高对学习记忆功能的影响。方法 Wistar大鼠神经肉瘤C6细胞培养于含醋酸铅的培养液中，于不同时间终止染铅，检测[ca2’]；及线粒体、内质网Ca^2 -ATP酶、Na^ 和K^ -ATP酶活力。结果 (1)0．2μmol／L染铅组：[Ca^2 ]i轻度升高，线粒体Ca^2 -ATP酶、Na^ 和K^ -ATP酶活力升高，内质网酶活力略增高；(2)1．0μmol／L染铅组：[Ca^2 ]；于染铅后0．5h升至最高，以后逐渐降低，波动于iL60～190nmol／L之间；线粒体、内质网Ca^2 -ATP酶、Na^ 和K^ -ATP酶于染铅后0．5h升至最高(分别为未染铅前酶活力的29．1、39．2、10．8和19．8倍)，2d后降至接近正常水平。结论 (1)铅可使Wistar大鼠神经肉瘤C6细胞Ca^2 浓度及线粒体、内质网Ca^2 -ATP酶、Na^ 和K^ -ATP酶活力增高；(2)当[Ca^2 ]i增高不显著时以线粒体Ca^2 -ATP酶、Na^ 和K^ -ATP酶活力增高为主；当[Ca^2 ]i急剧升高时，线粒体、内质网Ca^2 -ATP酶、Na^ 和K^ -ATP酶活力均明显增高，尤其是线粒体Ca^2 -ATP酶、Na^ 和K^ -ATP酶活力增高更为显著。     

3-硝基丙酸对沙土鼠海马CA1区锥体细胞超微结构的影响

目的　观察小剂量3-硝基丙酸(≤2 0mg/kg)对沙土鼠海马CA₁区锥体细胞超微结构的影响。方法　将沙土鼠腹腔注射不同剂量3-硝基丙酸或双蒸水后3d ,取海马CA₁区用戊二醛和锇酸固定,电镜下观察CA₁区锥体细胞层神经元细胞核和细胞器超微结构形态变化,用体视学方法计算每张照片线粒体和粗面内质网体面积变化。结果　实验组与对照组比较细胞核无明显变化,线粒体和粗面内质网轻度肿胀,体密度高于对照组。结论　小剂量3-硝基丙酸可引起神经元缺氧代偿性反应,无致死性损害。     

青岛市卫生技术人员2001年继续教育试题(三)

121、骨骼肌收缩时释放到肌浆中的Ca~(2+)被何处的钙泵转运? A、横管 B、肌膜 C、线粒体膜 D、肌浆网膜 E、粗面内质网122、下列生理过程需当时耗能的是     

日本鹌鹑睾丸的电镜观察

本文是通过透射电镜观察日本鹌鹑(Coturnix coturnix japonica)雄性生殖细胞及间质细胞的超微结构。精原细胞呈椭圆形。核圆形,异染色质少,常呈小块状,多靠近核被膜,核仁明显。染色质周围颗粒及染色质间颗粒清晰可见。线粒体有时呈空泡状,嵴短而稀疏,均匀分布于胞质中。精母细胞的异染色质散在分布于核质中,由颗粒状物质聚成团块,核仁明显。线粒体数量不多,分布情况如精原细胞。这与鸡的线粒体分布位置存有差异。粗面内质网和高尔基复合体发育良好,并可见环孔板。精子细胞核大而圆,异染色质少,呈稀疏的颗粒状分布在核被膜附近及分散于核液中。线粒体电子密度较高,内质网及高尔基复合体发育中等。间质细胞形状不规則,核仁清晰,内质网及线粒体丰富,二者有极性分布现象。线粒体嵴既有小管状,又有板层状。     

Reversible, hepatic, lysosomal phospholipidosis in rat induced by subchronic daily administration of trospectomycin sulfate

Trospectomycin sulfate is an experimental aminocyclitol antibiotic which has been shown previously to induce the formation of cytoplasmic lamellar bodies in rat and dog liver in subchronic experiments. The effect of repeated daily administration of trospectomycin sulfate on hepatic phospholipid levels and activities of marker enzymes for subcellular organelles was examined. Rats were treated for 30 or 90 days with 0, 50, or 250 mg/kg/day of trospectomycin sulfate prior to being killed, and another group was dosed for 90 days and then allowed to recover for 79 days prior to sacrifice. Transmission electron microscopy showed the presence of lamellar bodies in hepatocytes in both 50 and 250 mg/kg groups at 90 days but no other apparent changes in cellular morphology. Total phospholipids were increased significantly (1.6-fold) only at 90 days (P less than 0.01) and only in the 250 mg/kg group. Phosphatidylcholine, phosphatidylinositol, and two acidic lysosomal phospholipids, bis(monoacylglycero)phosphate and acylphosphatidylglycerol, accounted for 42, 35, and 21% of the increase in total phospholipids. Changes in the activities of marker enzymes were generally confined to the 250 mg/kg group at 90 days, with the largest and most significant increases being in the lysosomal enzymes acid phosphatase and hexosaminidase (P less than 0.01). Levels of all phospholipids and marker enzymes, with the exception of succinate dehydrogenase, were not significantly different from controls 79 days after cessation of dosing, and lamellar bodies had disappeared. We conclude that repeated trospectomycin sulfate treatment in rat induces a reversible, dose- and time-dependent lysosomal phospholipidosis in liver which is characterized by an increase in lysosomal enzymes and selected anionic phospholipids.     

Comparison of the toxicity of orally administered L-triiodothyronine (T3) in rat and cynomolgus monkey

Oral administration of L-triiodothyronine (L-T3) (0.015-1 mg/kg) for 30 days to mature rats or cynomolgus monkeys resulted in both species in a high mortality at 1 mg/kg (after 2 weeks of treatment) and a progressive loss in body weight. Dose-related elevations in plasma marker enzymes occurred, mainly after 1-2 weeks of treatment. The approximate no-effect dose for these changes was around 0.015-0.020 mg/kg for both rat and primate. The large elevations of leucine aminopeptidase (LAP) at 1 mg/kg L-T3 in monkey indicated hepatocellular toxicity although in the rat such large increases in alanine aminotransferase (ALT) and glutamate dehydrogenase (GLDH) were not seen. L-T3 also showed little toxicity to rat hepatocytes in vitro. High concentrations of L-T3 (7 x 10(-9) to 7 x 10(-7) M) had minimal effects on parameters of cell viability such as lactate dehydrogenase (LDH) leakage, chromium-51 release and [3H]leucine incorporation. Urinary enzymes in the rat showed a similar profile to those in plasma. Large rises in alkaline phosphatase (AKP) and N-acetyl glucosaminidase (NAG) at 1 mg/kg indicated possible proximal tubular damage although this was not supported histologically. Clinically, in both species L-T3 appeared more toxic to males than females but this was not supported histologically. The histological lesions observed were different in the 2 species. In the monkeys there was extensive lipid vacuolation of hepatocytes and changes in thyroid and adrenal cortex. In the rat there was fine, non-lipid vacuolation of hepatocytes and thyroid changes. In the rat, 2 previously unreported lesions were also noted. There were multinucleated cells in the renal distal tubular epithelium, and focal fibroplasia of serosal surfaces of abdominal viscera.     

急性黄磷中毒大鼠肝脏的脂质过氧化与肝损害的关系

本研究以黄磷3,6和9mg/kg ig,观察大鼠3,6,12和24h急性中毒时肝脏发生脂质过氧化程度、部位,以及与肝损害之间的关系。结果发现中毒大鼠肝匀浆、肝线粒体与微粒体MDA含量显著升高。肝匀浆Schiff碱荧光强度显著增强。肝线柱体与微柱体各自的标志酶SDH酶与G-6-P酶活性均显著降低,而且两亚细胞器的MDA含量升高与各自标志酶活性降低存在显著的负相关。肝TG含量显著升高与肝GSH含量显著降低的肝损害指标变化与脂质过氧化指标变化存在一定的平行关系。     

Enzymatic changes in rat liver associated with low and high doses of a peroxisome proliferator

The activities of a number of lipid-metabolizing and subcellular marker enzymes were measured in total homogenates and subcellular fractions prepared from the livers of male rats fed diets containing 0.05, 0.1, 0.3, and 0.5% of the hypolipidemic drug tiadenol, resulting in mean drug intake of 45, 90, 330, and 530 mg/day/kg body wt, respectively. In the total homogenates, a massive induction of palmitoyl-CoA hydrolase and peroxisomal palmitoyl-CoA oxidation accompanied by increased free CoASH and long-chain acyl-CoA content was observed at the highest dose levels whereas little change occurred up to 90 mg/day/kg/body wt. The palmitoyl-CoA synthetase activity increased slightly up to 90 mg/day/kg body wt, but higher doses resulted in decreased enzyme activity. Catalase activity increased with the dose to be elevated by a factor of approximately 1.6 at 330 mg/day/kg, whereas the activities of urate oxidase decreased. The specific activities of palmitoyl-CoA hydrolase and peroxisomal palmitoyl-CoA oxidation increased in all fractions, but most markedly in the cytosol. The changes in the activities and the distribution of subcellular marker enzymes and the increase of the peroxisome-associated polypeptide (PPA-80) are in keeping with a peroxisome proliferating effect resulting in formation of premature organelles with altered properties. Since high doses of many hypolipidemic drugs produce hepatic tumors and peroxisomal proliferation in rodents and since no increase in peroxisomes is found in human liver after therapeutic use of lower doses, the dose-response relationship is of interest for the evaluation of the toxicology of this class of agents.     

Acute Metabolic Effects of Olanzapine Depend on Dose and Injection Site

Atypical antipsychotics (AAPs), such as olanzapine (OLZ), are associated with metabolic side effects, including hyperglycemia. Although a central mechanism of action for the acute effects on glycemia has been suggested, evidence for peripheral versus central effects of AAPs has been mixed and has not been explored for an effect of OLZ on the respiratory exchange ratio (RER). Here, we tested the hypothesis that some inconsistencies in the glycemic responses are likely a result of different doses and central sites of injection. We also compared the effects of central versus peripherally administered OLZ on the RER of unsedated rats. Third ventricle infusion of OLZ at 0.3 mg/kg caused hyperglycemia within 30 minutes, with a higher dose (1.8 mg/kg) needed to elicit a similar response in the lateral ventricles. In contrast, 3 mg/kg of OLZ was needed to raise blood glucose within 30 minutes when given intragastrically, and 10 mg/kg resulted in a prolonged hyperglycemia lasting at least 60 minutes. Third ventricle injection of OLZ significantly decreased RER after 75 minutes, whereas intragastric OLZ resulted in a faster drop in RER after 30 minutes. Since changes in glycemia were most sensitive when OLZ was infused into the third ventricle, but effects on RER were more rapidly and efficaciously observed when the drug was given peripherally, these results raise the likelihood of a dual mechanism of action involving hypothalamic and peripheral mechanisms. Some discrepancies in the literature arising from central administration appear to result from the injection site and dose.     

Alteration of hepatocellular structure and function by thallium chloride: ultrastructural, morphometric, and biochemical studies

The effects of thallium chloride (TlCl3.4H2O) on hepatocyte structure and function were studied in male rats at 16 hr following treatment by ip injection with doses of 0, 50, 100, and 200 mg/kg. Ultrastructural examination of hepatocytes from thallium-treated rats showed a dose-related loss of ribosomes from the endoplasmic reticulum and proliferation of the rough endoplasmic reticulum segment. Generalized mitochondrial swelling and increased numbers of electron-dense autophagic lysosomes were also observed. Morphometric analysis of hepatocytes from thallium-treated rats disclosed a 3-fold increase in the volume density of the lysosomal compartment and a 1.3-fold increase in the volume density of mitochondrial. Surface density measurements of mitochondrial and endoplasmic reticulum membranes showed dose-related increases in the surface density of both inner and outer mitochondrial membranes as well as of the rough endoplasmic reticulum. These structural changes were associated with pronounced increases in the specific activities of the mitochondrial membrane-associated enzymes monoamine oxidase and ferrochelatase to 145 and 144% of control values, respectively, and a 42% decrease in the activity of aminolevulinic acid (ALA) synthetase. Similarly, structural alteration of the endoplasmic reticulum in thallium-treated rats was associated with concomitant impairment of the microsomal enzymes NADPH cytochrome c (P-450) reductase, aniline hydroxylase, and aminopyrene demethylase to a maximum of 49, 43, and 77% of activities seen in untreated controls, respectively. In contrast, the non-membrane-bound enzymes malate dehydrogenase, ALA dehydratase, and uroporphyrinogen I synthetase were unaltered in vivo following thallium treatment at any doses. These results indicate that thallium-induced alteration of hepatic biochemical processes may arise from physical disruption of the membranal integrity of subcellular organelles with which those processes are functionally associated. These findings are consistent with those from previous studies in demonstrating a positive quantitative correlation between metal-induced subcellular organelle membrane structural injury and impairment of associated biological functions in vivo.     

Activity of lysosomal system in mouse liver after taxol administration

• 1.1. The effect of taxol on selected lysosomal enzymes (cathepsin D, lysosomal lipase, β-glucuronidase, β-glucosidase, alanine aminopeptidase) in mouse hepatocytes after 24-hr treatment by increasing doses (0.75 mg/kg bw, 1.25 mg/kg bw and 2.5 mg/kg bw) was studied.
• 2.2. The segments were also taken from the mice for ultrastructural studies with the use of electron microscopy. The greatest changes in activity of enzymes at the taxol dose of 2.5 mg/kg bw were as follows: the activity of cathepsin D increased by 71%, that of alanine aminopeptidase increased by 103%, that of β-glucuronidase decreased by 45% and that of β-glucosidase decreased by 63%.
• 3.3. The significant changes observed in the hepatocyte ultrastructure were closely correlated with biochemical changes that were dependent on the taxol dosage.

     

Protective effect of ascorbic acid after single and repetitive administration of cadmium in Swiss mice

The aim of the study was to delineate the protective effect of ascorbic acid with plausible mechanism after single and repetitive cadmium administration to Swiss mice. The effects of single high dose administration of CdCl(2) (6?mg/kg) or ascorbic acid (AsA) (50?mg/kg) and chronic (three times) administration of Cd at low dose (2?mg/kg) or AsA at same dose (50?mg/kg) were compared in Swiss albino mice. Changes of lipid peroxidation [determined by the malonyldialdehyde (MDA) concentration] were taken as a measure of the oxidative stress intensity. Lipid fatty acid's unsaturation related to the permeability of cell membranes was also examined. Mobilization of the immune system was determined by analyzing changes in antioxidant concentrations of AsA and glutathione (GSH), and by measuring the activation of antioxidant enzymes SOD, GPx and CAT. In addition, the level of free polyamines and variation in their proportions were examined. In conclusion, exposure to higher levels of cadmium will have more deleterious effects on the body rather than chronic exposure at lower levels with this toxic metal, while this study clearly demonstrated the protective effects of AsA in a mouse model.     

Protective effect of ascorbic acid after single and repetitive administration of cadmium in Swiss mice

The aim of the study was to delineate the protective effect of ascorbic acid with plausible mechanism after single and repetitive cadmium administration to Swiss mice. The effects of single high dose administration of CdCl₂ (6?mg/kg) or ascorbic acid (AsA) (50?mg/kg) and chronic (three times) administration of Cd at low dose (2?mg/kg) or AsA at same dose (50?mg/kg) were compared in Swiss albino mice. Changes of lipid peroxidation [determined by the malonyldialdehyde (MDA) concentration] were taken as a measure of the oxidative stress intensity. Lipid fatty acid’s unsaturation related to the permeability of cell membranes was also examined. Mobilization of the immune system was determined by analyzing changes in antioxidant concentrations of AsA and glutathione (GSH), and by measuring the activation of antioxidant enzymes SOD, GPx and CAT. In addition, the level of free polyamines and variation in their proportions were examined. In conclusion, exposure to higher levels of cadmium will have more deleterious effects on the body rather than chronic exposure at lower levels with this toxic metal, while this study clearly demonstrated the protective effects of AsA in a mouse model.     

Chronic intravenous toxicity studies of potassium clavulanate and BRL28500 in dogs

The chronic toxicity of potassium clavulanate (CVA-K) and BRL28500 were evaluated using dogs in 26-week intravenous administration studies followed by a 5-week off-dose period. The doses for CVA-K and BRL28500 were 10, 20, 50 and 100 mg/kg (p.f.a.), and 80, 160, 320 and 800 mg/kg (p.f.a.) respectively. There were no deaths in either of the groups. For general condition, dogs dosed with CVA-K at 100 mg/kg showed reddening of the skin and mucous membranes, shaking of the head, facial oedema, a decrease in food intake and a reduction in body weight. Also some dogs of the same group showed decreased spontaneous activity, emaciation and signs of dehydration. In the BRL28500 treatment groups, there was reddening of the skin and mucous membranes, vomiting and salivation at 800 mg/kg. Urinalysis of dogs dosed with CVA-K showed occasional dark yellow coloration of the urine. There was also a very weak and equivocal response or positive reaction for protein, occult blood, and urine sugar in some animals at 100 mg/kg. Some dogs dosed with BRL28500 also showed either a very weak and equivocal response or slight positive reaction for occult blood at 320 mg/kg and above, and dark yellow coloration of the urine at 800 mg/kg. Haematological examination of the CVA-K groups showed increases in leukocyte count and platelet count at the highest dose of 100 mg/kg. No haematological abnormalities were noted in any of the BRL28500 groups. Serum biochemical studies of dogs dosed with CVA-K revealed a decrease in total protein at 50 mg/kg and above, and increases in Al-P, total bilirubin, GPT, BUN and creatinine at 100 mg/kg. In the BRL28500 treatment groups, there were increases in total cholesterol and triglyceride at 160 mg/kg and above. In dogs dosed with CVA-K there was an increase in liver weight at 100 mg/kg. Histopathological examination showed a ground glass-like appearance of the hepatocyte cytoplasm and also altered distribution of PAS positive material at 50 mg/kg and above. In the BRL28500 groups, there was an increase in liver weight at 320 mg/kg and above. There were the same ground glass-like appearance in hepatocytes and altered distribution of PAS positive material at 800 mg/kg. In view of the above results, the maximum non-effect dose levels in the present studies were considered to be 20 mg/kg for CVA-K and 80 mg/kg for BRL28500.(ABSTRACT TRUNCATED AT 400 WORDS)