Effects of ethyl-CPIB (clofibrate) on tissue lipoprotein lipase and plasma post-heparin lipolytic activity in rats

The role of LPL in reducing the serum triacylglycerol concentration was investigated in rats fed a high sucrose diet containing 0.25% (w/w) ethyl-CPIB. Compared with sucrose-fed controls, drug treatment resulted in a fall in adipose tissue LPL activity and a rise in enzyme activity in thigh and heart muscle. Serum post-heparin lipoprotein lipase activity after a high dose of heparin was lower in ethyl-CPIB-treated rats than controls, but after a low dose of heparin the values were similar. The amount of LPL activator was decreased by the drug. Thus, the low serum triacylglycerol concentration observed in the ethyl-CPIB-treated rats cannot be explained by changes in functional LPL activity. The plasma triacylglycerol-lowering effect of the drug could be explained by the observed decrease in triacylglyerol output by the liver.     

皱褶假丝酵母脂蛋白脂酶的分离纯化及酶学性质的研究

目的从皱褶假丝酵母的发酵液中纯化脂蛋白脂酶,并对其酶学性质进行研究。方法利用硫酸铵盐析、DEAE-Sepharose Fast Flow和Phenyl Sepharose CL-4B层析等方法进行纯化,利用SDS-PAGE、PAGE和HPLC法进行鉴定。结果获得的脂蛋白脂酶为单一组分,相对分子质量为34 kDa;此酶在50℃、pH6～9时保持稳定;在最适条件下测得其米氏常数(Km)为3.4×10-4mol·L-1;用等电点沉淀法测得脂蛋白脂酶的pI=5.5;Hg+、Cu2+、Ag+和SDS是脂蛋白脂酶的抑制剂,Mg2+和Triton X-100对此酶有激活作用。结论文中方法获得了皱褶假丝酵母脂蛋白脂酶的酶学性质,对此酶在食品、医药和生物技术等领域的应用提供了理论支持。     

低氧条件下耐力运动对大鼠血浆三酰甘油的影响

目的探讨低氧条件下耐力运动对大鼠血浆三酰甘油的影响。方法选取雄性SD健康大鼠60只，随机分为6组，即常氧安静组（A）、常氧运动组（B）、低氧安静组（C）、高住高练组（D）、高住低练组（E）、低住高练组（F），A、B、F组在常氧下居住，C、D、E组在低氧下居住。模拟低氧舱内氧浓度为15．4％左右，相当于海拔2500m。B、E组每天以25m／min在常氧动物跑台上运动，D、F组每天以20m／min在相当于海拔2500m低氧环境动物跑台上运动。运动各组要求60min／d、6d／周，共实验6周。结果发现高住高练组、高住低练组和低住高练组与平原训练组相比较，三酰甘油浓度下降幅度更为明显，脂蛋白脂肪酶和骨骼肌脂蛋白脂肪酶的活性提高更明显。结论低氧训练对血脂代谢的改善与其提高了脂蛋白脂肪酶的活性紧密相关。     

Effects of dichlorvos (DDVP) inhalation on the activity of acetylcholinesterase in the bronchial tissue of rats

The experiments presented here deal with the effects of the inhalation of dichlorvos [dimethyl-(2,2 dichlorvinyl)-phosphate, DDVP] vapor on acetyl-cholinesterase (ACHE) activity in rat bronchial tissue. Exposure to DDVP concentrations of 0.8 and 1.8 g/l for 3 days reduced ACHE activity in the bronchial tissue (62.8±0.8 and 51.6±1.6% of the control), but did not elicit any changes in blood ACHE activity (101±4.5% of the control each). Higher concentrations (4.3 g/l) induced a decline in ACHE activity also in the blood (38.2±1.1% of the control). In the histochemical preparations used to demonstrate CHE activity in bronchial tissue (thiolacetic acid method), a staining of the bronchial glands and smooth muscles characteristic of the enzyme activity was strongly reduced after exposure of the animals to even the lowest dose applied (0.2 g/l). The question of whether localized inhibition of ACHE in the bronchial tissue might cause increases in airway resistance due to activation of a broncho-bronchial reflex is discussed. This efferent cholinergic mechanism has been found to be at least partly responsible for maintenance of bronchospasm and hypersecretion in chronic obstructive deseases of the respiratory system.     

Effects of clofibrate,bezafibrate, fenofibrate and probucol on plasma lipolytic enzymes in normolipaemic subjects

Summary Ten male, normolipaemic, non-obese subjects were given clofibrate 2g daily, fenofibrate 300 mg daily, bezafibrate 600mg daily and probucol 1g daily for eight days, in a crossover study with a wash-out period of 4–8 weeks between each drug regimen. Clofibrate, fenofibrate and bezafibrate caused a significant decrease in serum triglycerides, total cholesterol and LDL-cholesterol concentrations. Probucol caused a significant increase in serum LDL-cholesterol concentration. Serum HDL-cholesterol concentration was significantly increased by bezafibrate and significantly decreased by probucol. All drugs but probucol led to a significant rise in the activity of the plasma lipoprotein lipase; there was not a significant increase in the activity of plasma hepatic lipase after any drug. The activity of plasma lecithin: cholesterol acyltransferase was significantly increased by fenofibrate and probucol. Analysis of the correlations between serum lipids and plasma lipolytic enzymes suggests that the mechanism of the hypolipidaemic action of clofibrate and bezafibrate might be related to increased catabolism of triglyceride-rich particles; that of fenofibrate and probucol was less clear and might be multifactorial in origin.     

Dose-dependent effects of chronic ethanol on mouse adipose tissue lipase activity and cyclic AMP accumulation

1. The effects of two chronic ethanol treatment schedules, which produce different plasma ethanol concentrations, on the specific activities of adipose tissue lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) have been investigated in brown and white fat.
2. Mice provided with 20% ethanol solution as sole drinking fluid for 28 days consumed between 13 and 15 g ethanol kg⁻¹ body weight day⁻¹ over days 22–28. The mean plasma ethanol concentration was 4.94±1.4 mM (n=8) at 09 h 00 min on day 28 when the lipase assays were performed. Mice given ethanol in a liquid diet for 7 days consumed between 15 and 18 g ethanol day⁻¹ over days 3–7. The mean plasma ethanol concentration was 15.9±4.7 mM (n=8) at 09 h 00 min on day 7. These concentrations of ethanol had no effect on the activity of either LPL or HSL in vitro.
3. LPL activity in white and brown fat (expressed as nmol fatty acids released h⁻¹ mg⁻¹ acetone powder) was unaltered 60 min following an acute injection of ethanol (2.5 g kg⁻¹, i.p.) which produced a mean blood ethanol level of 37.5±6.7 mM. HSL activity in white fat (expressed as nmol fatty acid released h⁻¹ mg⁻¹ protein) was also unaffected by this acute dose of ethanol, but the activity in brown fat was significantly reduced: 3.07±0.30 (n=8) after ethanol compared to 4.36±0.25 (n=12) in controls (P<0.01).
4. LPL activity in white fat was little altered by either of the chronic ethanol treatment schedules whilst LPL activity in the brown fat from the same animals was significantly increased compared to the respective control values: 0.27±0.03 (ethanol drinking), control: 0.16±0.01; 0.79±0.14 (ethanol liquid diet), control: 0.39±0.05.
5. HSL activity in white fat was significantly increased by the chronic drinking treatment (7.7±0.5; control: 3.78±0.17, n=8) at the same time that the activity in brown fat was reduced (3.76±0.2; control: 4.74±0.16). The ethanol liquid diet also reduced HSL activity in brown fat but had negligible effect in white fat.
6. The effects of the two chronic ethanol treatments on adenosine 3′ : 5′-cyclic monophosphate (cyclic AMP) accumulation in brown and white fat were very similar, both qualitatively and quantitatively, to the effects on HSL.
7. It has been shown that brown and white adipose tissues respond differently to the presence of chronic ethanol and that the response is dependent both upon the concentration of ethanol and the nature of the diet with which the ethanol is administered. The effects of ethanol on adipose tissue HSL activity appear to be mediated via changes in the tissue cyclic AMP level and, in this respect, brown fat is more sensitive to ethanol than white fat.

     

大黄多糖对糖尿病动脉粥样硬化大鼠血糖、血脂、肝脂酶活性的影响

目的 观察大黄多糖对糖尿病动脉粥样硬化大鼠血糖、血脂、肝脂酶活性的影响.方法 将Wistar大鼠分为正常组和建模组,建模成功的糖尿病动脉粥样硬化大鼠随机分为模型组(糖尿病AS组)、大黄高、中、低剂量组,测定血脂生化指标及血浆中HL活性并制备主动脉病理切片.结果 在高剂量大黄多糖的作用下,糖尿病动脉粥样硬化大鼠的血糖、总胆固醇、甘油三酯、低密度脂蛋白胆固醇明显降低,血浆肝脂酶活性增加.结论 大黄其有效成分大黄多糖能降糖、降血脂、增加糖尿病动脉粥样硬化大鼠血浆中HL活性.防止糖尿病大血管并发症的发生发展.     

Influence of two non-steroidal anti-inflammatory drugs on lipolysis and on plasma post-heparin lipoprotein lipase activity in normal man

Summary Indomethacin 50 mg i.v. or p.o. and diclofenac sodium 50 mg p.o produced a prompt and significant increase in plasma free fatty acid concentration. In 10 subjects who took indomethacin 150 mg/d p.o. for 3 days, plasma post-heparin lipoprotein lipase activity was also significantly increased. The same effect occurred in 9 subjects treated for 3 days with diclofenac sodium 50 mg t.d.s. Since both indomethacin and diclofenac sodium are potent inhibitors of prostaglandin synthetase, these findings are consistent with the hypothesis that prostaglandins are involved in the feed-back regulation of lipolysis, and mediate the inhibitory effect of lipolysis on lipoprotein lipase activity.Part of this work was presented at the VIIth International Symposium on Drugs Affecting Lipid Metabolism, Milano, May 28–31, 1980     

Effect of oral mesoglycan on plasma lipoprotein concentration and on lipoprotein lipase activity in primary hyperlipoproteinemia

Mesoglycan extracted from calf aorta was orally administered (96 mg/day) to 15 patients with primary hyperlipoproteinemia: 4 type IIA, 4 type IIB, 6 type IV and one type V. In the seven hypertriglyceridemic patients the drug after two months of treatment reduced total and VLDL-triglyceride from 701 mg/dl to 423 mg/dl (p less than 0.025) and from 562 mg/dl to 377 mg/dl (p less than 0.025) respectively and increased lipoprotein lipase activity from 19.7 mumol/l/min to 27.8 mumol/l/min (p less than 0.05). No change was observed in the group with type IIA-IIB hyperlipoproteinemia.     

In vitro effects of glucidamine on adrenergic stimulated lipolysis and on lipoprotein lipase activity in human adipose tissue

Glucidamine, a purified glycoprotein-mucopolysaccharide complex displays dose-dependent lipolytic effect on human adipose tissue in vitro. On adipose tissue lipoprotein lipase activity glucidamine exhibits an heparin-like effect in eluting the enzyme from the tissue stores to the medium of incubation. No activating effects of glucidamine on lipoprotein lipase eluted from human adipose tissue was observed.     

伊贝沙坦对胰岛素抵抗大鼠脂蛋白脂酶的影响

目的探讨伊贝沙坦改善胰岛素抵抗（IR）、减少动脉粥样硬化疾病发生的危险因素的作用。方法用果糖喂养6周龄雄性SD大鼠8周造成IR,并给予伊贝沙坦干预后,行空腹血糖（FPG）、空腹血清胰岛素（FINS）、血清甘油三脂（TG）、胆固醇（TC）、极低密度脂蛋白（VLDL）、游离脂肪酸（FFA）和血浆脂蛋白脂酶（LPL）活性的测定,分别与对照组比较。结果果糖喂养组的血压、FINS、TG、TC、VLDL及FFA均高于对照组和药物处理组（P〈0.05或P〈0.01）,而胰岛素敏感指数（ISI）及LPL活性却均低于对照组和药物处理组（P〈0.05）。结论伊贝沙坦可以减轻果糖饲料喂养SD大鼠的IR、降低血压、明显提高LPL的活性及减轻机体脂质代谢紊乱。     

Hypocholesterolemic activity of dipyridamole: effects on chick plasma and lipoprotein composition and arachidonic acid levels

We have studied the effects of dipyridamole treatment on chick plasma and lipoprotein composition in postprandial and fasting (12 h) conditions. Plasma cholesterol levels were higher in fasted than in fed chicks, whereas triglycerides declined during starvation. Dipyridamole treatment reduced plasma cholesterol content, mainly of the free cholesterol fraction. In postprandial conditions, total cholesterol content of high and low density lipoproteins decreased in a similar proportion to that observed in plasma. However, cholesterol and other chemical constituents of intermediate and very low density lipoproteins were more drastically reduced by dipyridamole than in plasma. Total amounts of these lipoprotein fractions were also reduced about 50%. The effects of dipyridamole in fasted animals were not significant. To our knowledge, this is one of the first reports about the response of lipoprotein cholesterol to dipyridamole treatment. A strong decrease was also found in the arachidonic acid content of plasma phospholipids and cholesterol esters fractions.     

脂蛋白脂酶基因PvuⅡ酶切位点多态性与胰岛素抵抗关系的研究

目的旨在探讨脂蛋白脂酶基因第6内含子PvuⅡ酶切位点多态性与胰岛素抵抗、2型糖尿病的发生之间是否有关联。方法随机选取163例2型糖尿病患者作为病例组，106例正常人作为正常对照组，对第6号内含子PvuⅡI酶切位点进行多态性分析。结果病例组中P＋P＋组高密度脂蛋白胆固醇水平明显低于P-P-组，而血清三酰甘油、胰岛素抵抗指数指标水平高于P-P-组。结论PvuⅡ酶切位点多态性与2型糖尿病中胰岛素抵抗有关。     

Follow up studies on the respiratory pattern and total cholinesterase activities in dichlorvos-poisoned rats

A human prospective study confirmed that the severity and time-course of organophosphate poisonings depend on the compound. Our purpose was to assess the ventilation at rest and cholinesterase activities from 5min to 72h in rats poisoned with dichlorvos at 40% of the MLD (5.12mg/kg). Ventilation at rest was recorded by whole body plethysmography and core temperature by infrared telemetry (DSI system). Results are expressed as mean±SEM. Statistical analyses used two-way ANOVA. Dichlorvos induced the onset of respiratory effects within 5min and hypothermia which peaked at 15min, both reversed within 90min post-injection. Dichlorvos significantly decreased respiratory frequency, resulting from an increase in expiratory time and associated with increased tidal volume. Tissues and whole blood cholinesterase activities were significantly decreased until the end of experiment. Our study showed that an inhibition of cholinesterase was correlated with an effect on respiratory functions at 15min and 60min. However, 24h post-poisoning, the increase in cholinesterase activity was not completed while ventilatory parameters were within the normal range. Respiratory effects were both qualitatively and quantitatively similar to those induced by diethylparaoxon. However the effects strongly differed between diethylparaoxon lasting hours while dichlorvos lasted tens of minutes.     

Effect of statins on lipoprotein receptor expression in cell lines from human mast cells and basophils

Objective Statins are potent inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase and widely used to treat hyperlipidaemia. Apart from their direct lipid-lowering effects, statins may also influence lipid metabolism through modulation of low-density lipoprotein (LDL) receptors. Basophils and mast cells have been reported to express LDL receptors and have been implicated in atherogenesis. The aim of this study was to investigate the effects of statins on the interactions of ¹²⁵I-LDL with purified primary human blood basophils, a human basophil cell line, KU812, and a human mast cell line, HMC-1.Methods Direct binding experiments were carried out with the primary basophils and KU812 as well as HMC-1 cells before and after pretreatment of the cells with atorvastatin, simvastatin, or cerivastatin. The effects of these three statins on the LDL-uptake and degradation as well as on thymidine incorporation in the cells were also studied.Results Primary basophils, HMC-1 and KU812 cells expressed two classes of LDL binding sites. Exposure to atorvastatin, simvastatin or cerivastatin increased significantly (P<0.05) the number of ¹²⁵I-LDL binding sites on primary basophils and HMC-1 as well as KU812 cells. The effects of the statins were dose dependent. The statins also enhanced the uptake and degradation of LDL in primary basophils, HMC-1 and KU812 cells. The increase in the number of LDL binding sites induced by statins was abolished by mevalonic acid (200 mol/l). Statins had no effect on the thymidine incorporation into the cells in an unstimulated condition.Conclusion Our results provide evidence for the upregulation of LDL binding sites on human basophils and mast cells by statins. We hypothesise that effects of statins on the lipid metabolism might also involve basophils and mast cells.     

Effects of chronically administered nicotine and saline on motor activity in rats

This study investigated the differential effects of chronically administered nicotine and saline on motor activity in the rat. Nicotine was administered via a subcutaneously implanted osmotic minipump to effect an 8 hour off, 16 hour on, flow. Subjects were 48 male and 48 female albino rats, each about 165 days old. Activity was monitored every hour for 192 consecutive hours. Results indicated that the female animals were more active than the males, and that animals receiving nicotine were significantly more active on the first two days of drug administration than control animals; however, by the fourth day there were no significant differences between the activity levels of animals that received nicotine and those of control animals.     

Reduction of adipose tissue lipoprotein lipase activity as a result of in vivo administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin to the guinea pig

Within 1 hr of intraperitoneal administration of 1 microgram 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)/kg, lipoprotein lipase (LPL) activity was reduced 38% from initial levels in the adipose tissue of the guinea pig. Maximal depression was observed after 2 days and persisted throughout the 10-day observation period. Oral administration of glucose restored LPL activity in TCDD-treated animals after 1 day but only partially after 2 and 5 days, and had no effect after 10 days of exposure. Although initial (2-day) serum insulin levels were depressed, the inability of glucose to restore LPL activity after prolonged exposure was not due to malabsorption of glucose nor to changes in serum thyroxine or insulin concentration. TCDD also inhibited the lipolytic pathway in the adipocyte, but had no effect on hormone sensitive lipase (HSL). Since HSL and LPL are reciprocally regulated, it was concluded that TCDD acts on the adipocyte to uncouple HSL-LPL reciprocity as well as to reduce LPL production.