卡托普利对病毒性心肌炎小鼠心肌线粒体结构及其酶活性的影响

目的　研究卡托普利对病毒性心肌炎小鼠心肌线粒体结构和三磷酸腺苷 (ATP)酶活性变化的影响。方法　将雄性Balb/c小鼠随机分为柯萨奇病毒B3 (CVB3 )感染组、CVB3 感染加卡托普利治疗组和对照组。以d3、d14为两个时相点 ,比较线粒体超微结构 ,线粒体Na+ K+ ATP酶、Ca2 + ATP酶活性变化。结果　感染组心肌细胞线粒体结构破坏 ,线粒体Na+ K+ ATP酶、Ca2 + ATP酶活性较对照组显著下降 (P均 <0 .0 1)。卡托普利治疗组各时相点线粒体结构破坏较轻 ,线粒体Na+ K+ATP 酶、Ca2 + ATP酶活性较感染组明显增高 (P均 <0 .0 5 )。结论　病毒性心肌炎早期即可见心肌线粒体结构破坏 ,ATP酶活性下降。卡托普利可有效保护心肌线粒体结构和功能     

Effects of adrenocortical steroids and of adrenocorticotrophic hormone on (Na+-K+)-ATPase in immature cerebral cortex.

The effect of cortisol, methylprednisolone, and ACTH on (Na+-K+)-ATPase activity in developing cerebral cortex has been measured. Stimulation of (Na+-K+)-ATPase by these agents has been found in whole brain homogenates of kittens as early as age 8 days, and in whole homogenates and light microsomal fractions in young rats at 14 and 28 days. (Na+-K+)-ATPase activity in animals treated with corticosteroids or ACTH for 4 days was found to be 15--30% higher than activity in littermate controls. Brain potassium concentrations was increased in 14-day-old rats treated with methylprednisolone.     

不同剂量卡托普利对病毒性心肌炎小鼠心肌线粒体的保护效应

目的研究不同剂量卡托普利对病毒性心肌炎小鼠心肌线粒体结构和ATP酶活性变化的影响。方法雄性Balb/c小鼠随机分为柯萨奇病毒B3（CVB3）感染组、CVB3感染加不同剂量卡托普利治疗组（10、30、100mg/kg,2次/d）和对照组。d14电镜观察线粒体超微结构,生化方法测定线粒体Na＋-K＋-ATP酶、Ca2＋-ATP酶活性。结果各剂量卡托普利治疗组线粒体膜Na＋-K＋-ATP酶、Ca2＋-ATP酶活性均较感染组高,但小剂量组差异无显著性（P〉0.05）,且线粒体溶解破坏,失去完整性;中、大剂量组差异具有显著性（P〈0.01）,且线粒体结构改变与同病变期感染组比较明显较轻。结论小剂量卡托普利治疗无明显心肌线粒体保护效应,中、大剂量卡托普利心肌线粒体保护效应明显。     

吸入一氧化氮对感染性急性肺损伤时红细胞变形能力的影响

目的 研究吸入一氧化氮(NO)对红细胞变形能力的影响及其可能机制.方法 将3～4周龄健康雄性幼猪30只麻醉后经口气管插管进行机械通气,随机分为4组.(1)正常组(C,n=6)单纯机械通气;(2)正常幼猪加吸入NO(CNO,n=4);(3)模型组(M,n=10)单纯机械通气;(4)模型制备加吸入N0(MNO,n=10).M和MNO组动物经腹腔注射标准大肠杆菌诱发急性肺损伤(ALI),C及CNO组用无菌生理盐水替代.MNO组出现ALI后进行吸入NO(10×10-6),治疗24h,CNO组则机械通气4 h后(0 h)开始吸入NO并维持24 h.在实验基础状态、ALI时(0 h)、ALI后12以及24 h测血细胞比容、全血黏度、红细胞膜Na+-K+-ATP酶、Ca2+-Mg2+-ATP酶活性及红细胞内丙二醛(MDA)浓度.结果 CNO组吸入NO后12、24 h高切率下血液黏度(反映红细胞变形能力)、红细胞膜Na+-K+-ATP酶、Ca2+-Mg2+-ATP酶活性及红细胞内MDA浓度变化不大.动物出现ALI时其红细胞变形能力降低,红细胞膜Ca2+-Mg2+-ATP酶、Na+-K+-ATP酶活性均下降,红细胞内MDA浓度升高(P＜0.05).MNO组在吸入NO 12 h时红细胞变形能力改善,红细胞膜Ca2+-Mg2+-ATP酶、Na+-K+-ATP酶活性均较M组高(P＜0.05),红细胞内MDA浓度则低于M组(P＜0.05);但这些参数在吸入NO 24 h与C组比较差异均无显著性(P＞0.05).结论 ALI时红细胞变形能力显著下降,可以因吸入NO而改善,但作用不持久.     

The role of active sodium and potassium transport in hyponatremic states in infancy and childhood

Erythrocytes from 14 infants and children with serum sodium concentrations of 125 mmol/l or less were analyzed for total and Na+, K+-ATPase, sodium and potassium content and ATP concentrations to evaluate the role of active Na+-K+ transport in hyponatremia. In six out of nine patients, with a duration of hyponatremia of more than 48 hours low Na+, K+-ATPase activities and high erythrocyte sodium concentrations and Na+-K+ ratios were found indicating that a decreased Na+, K+-ATPase activity leading to an increased intracellular accumulation of sodium ions may have reduced the extracellular sodium concentration. Three subjects with large sodium losses had high Na+, K+-ATPase activities and normal erythrocyte sodium concentrations. In five cases of hyponatremia with a duration of less than 24 hours the variables indicating active Na+-K+ transport were normal. The therapeutic implications with sodium substitution and the use of drugs affecting active Na+-K+ transport are discussed.     

Developmental changes in erythrocyte Na(+),K(+)-ATPase subunit abundance and enzyme activity in neonates

AIM: To study the relation between erythrocyte Na(+),K(+)-ATPase subunit isoform composition, Na(+),K(+)-ATPase activity, and cation pump function in preterm and term neonates. DESIGN: Erythrocyte Na(+),K(+)-ATPase subunit isoform abundance, Na(+),K(+)-ATPase activity, and cation pump function were studied in blood samples obtained from 56 preterm neonates of 28-32 weeks gestation (group 1), 58 preterm neonates of 33-36 weeks gestation (group 2), and 122 term neonates (group 3) during the first two postnatal days. RESULTS: alpha(1) isoform abundance was higher and beta(2) isoform abundance was lower in group 1 than in group 3 (p = 0.0002). alpha(2) and beta(1) isoform abundance did not change with maturation and there was no evidence for the presence of the alpha(3) isoform. Gestational age was inversely related to Na(+), K(+)-ATPase activity (p = 0.0001) and directly related to intracellular Na(+) concentration (p = 0.0025). CONCLUSIONS: Expression of the alpha(1) and beta(2) Na(+),K(+)-ATPase subunit isoforms is developmentally regulated. The increased abundance of alpha(1) isoforms of immature neonates translates to increased ATPase activity. The lower intracellular Na(+) concentration of immature neonates suggests that their erythrocyte Na(+),K(+)-ATPase cation pump function may also be increased.     

Characteristics of active sodium and potassium transport in erythrocytes of healthy infants and children

Erythrocytes were analysed for adenosine triphosphatase (total and sodium-potassium activated) activities, concentrations of sodium and potassium ions and ATP in normal individuals from birth to adulthood age. A decrease of Na+, K+-ATPase activity and an increase of the sodium concentration was seen in infants aged 1-3 and 4-8 months. A decrease of Na+, K+-ATPase was seen during puberty. A correlation was seen between the Na+, K+-ATPase activity and the Na+-K+ ratio. Different influences which might lead to the observed changes in Na+, K+-ATPase activity and erythrocyte sodium concentration are discussed.     

Erythrocyte sodium-potassium transport in cystic fibrosis.

Erythrocytes from 15 patients with cystic fibrosis (CF) aged 8 mo to 22 y (mean age 12.8 y) were analyzed for Na+,K(+)-ATPase activity and sodium, potassium, and ATP concentrations. Sodium concentrations and Na(+)-K+ ratio of erythrocytes were statistically significantly lower in the CF patients [6.6 (SD 1.9) versus 9.2 (SD 1.1) mmol/L (p less than 0.01) and 0.070 (SD 0.023) versus 0.104 (SD 0.016) mmol/L (p less than 0.01), respectively]. The Na+,K(+)-ATPase activity was similar compared with that of reference individuals [536 (SD 100) versus 488 (SD 92) nmol inorganic phosphate/mg protein/h]. Intraerythrocyte sodium concentration and Na(+)-K+ ratio were thus lower in relation to the recorded Na+,K(+)-ATPase activities in controls, indicating a change of the passive transmembrane movements of sodium ions in CF. There was a rise of erythrocyte sodium and Na(+)-K+ ratio despite unchanged Na+,K(+)-ATPase activity after regular infusion of a fat emulsion rich in essential fatty acids, inferring that an altered membrane composition by essential fatty acid deficiency could explain the low intracellular sodium concentration in CF.     

Erythrocyte membrane acetylcholinesterase, Na+, K+-ATPase and Mg2+-ATPase activities in patients with classical galactosaemia

BACKGROUND: Classical galactosaemia is commonly presented by high blood galactose (Gal) and galactose-1-phosphate (Gal-1-P) levels followed by mental retardation, seizures, etc. dependent on the mutation of the patients. AIM: To evaluate Gal and Gal-1-P in the blood of patients and to correlate their levels with their erythrocyte membrane acetylcholinesterase (AChE), Na+,K+-ATPase and Mg2+-ATPase activities. METHODS: Blood was obtained from nine patients on poor diet (group B) followed by a 30-d strict diet (group A) and controls (group C) in order to evaluate Gal and Gal-1-P in Guthrie cards and to correlate their concentrations with the above enzyme activities, which were measured spectrophotometrically. RESULTS: With the patients on a "loose" diet, AChE, Na+,K+-ATPase and Mg2+-ATPase activities were found to be decreased, as compared with those on strict diet and controls. Significantly (p<0.01) inverse correlation coefficients of the enzyme activities were found with Gal-1-P levels. CONCLUSION: (a) AChE, Na+,K+-ATPase and Mg2+-ATPase activities were determined to be decreased in poorly controlled patients with classical galactosaemia. (b) The enzyme activities were inversely correlated with the Gal-1-P blood levels. (c) Since Na+,K+-ATPase in the erythrocyte membranes is the isomer of Na+,K+-ATPase distributed in many tissues and in the brain, evaluation of the enzyme activity in the erythrocytes could be a useful peripheral marker of Gal-1-P toxicity.     

Effects of prolactin on Na+K(+)-ATPase activity in the nephron during maturation in the rat.

The effect of prolactin (PRL) on renal Na+K(+)-ATPase was investigated in 7-d-old neonatal rats. Animals were treated by bromocriptine (Br; a blocker of endogenous PRL secretion), and the enzyme activity was compared with that of untreated controls. Na+K(+)-ATPase was determined in renal sections in the medullary thick ascending limb of Henle's loop and in the distal tubule by cytochemistry. In the distal tubule, Na+K(+)-ATPase activity was significantly lower in Br-treated animals than in controls (330 +/- 169 versus 558 +/- 146 pmol inorganic phosphate/mm/h, respectively); values did not differ in the medullary thick ascending limb of Henle's loop between Br-treated and control animals (132 +/- 74 versus 165 +/- 113 pmol inorganic phosphate/mm/h, respectively). In vitro effects of PRL were investigated by determining the enzyme activity after incubation of renal sections from Br-treated and untreated animals with different concentrations of PRL. Results suggest that PRL may affect renal Na+K(+)-ATPase activity in the distal tubule in the neonatal period but do not support a major role of PRL in the enzyme maturation.     

肥胖儿童红细胞钙镁水平及ATP酶活性与高血压关系的探讨

目的     

室间隔缺损合并心力衰竭治疗后红细胞钙离子代谢变化

本文分别探讨了开搏通和地高辛对室间隔损合并心力衰竭时患红细胞Ｃａ＾２＋代谢的影响。     

THE ISOPRENOID PATHWAY AND THE PATHOGENESIS OF REYE'S SYNDROME

The isoprenoid pathway produces three key metabolites: endogenous digoxin (regulator of neurotransmitter uptake), dolichol, and ubiquinone (free radical scavenger). Because a mitochondrial dysfunction has been described in Reye's syndrome, we thought it pertinent to assess the pathway in this disease. Since endogenous digoxin can regulate neurotransmitter transport, the pathway also was assessed in patients with right hemispheric, left hemispheric, and bihemispheric dominance to find out the role of hemispheric dominance in its pathogenesis. The plasma/serum activity of HMG CoA reductase, magnesium, digoxin, dolichol, ubiquinone, tryptophan/tyrosine catabolic patterns, free radical, and lipid levels aswellas (red blood cell) RBC Na + -K + ATPase activity were measured in the above mentioned groups. Results: In the patient group as well as in individuals with right hemispheric dominance similar patterns were obtained. There was elevated digoxin and dolichol levels with low levels of ubiquinone in patients with Reye's syndrome as well as in those with right hemispheric dominance. The serum magnesium and RBC Na + -K + ATPase activity were reduced. There also was an increase in tryptophan catabolites and a reduction in tyrosine catabolites as well as increased free radical levels. Reye's syndrome is associated with an upregulated isoprenoid pathway, elevated hypothalamic digoxin secretion, and right hemispheric chemical dominance.     

高胆红素血症新生大鼠脑组织Na~+-K~+-ATP酶活力的研究

目的：探讨胆红素神经毒性的作用环节,研究胆红素脑病发病机理。方法：72只新生7d SD大鼠随机分为对照组(C组)和实验组(T组),T组又根据腹腔注射胆红素剂量的依次增加分为T1,T2,T3,T4和T5组。检测各组脑组织和血清中胆红素含量,定磷法测定脑组织中Na+ K+ ATP酶(Na+ K+ ATPase)活力。结果：给药后4 h和8 h均随着腹腔注射胆红素量的增加,血清总胆红素浓度、脑组织内胆红素含量逐渐增加,脑组织Na+ K+ ATPase活力则逐渐降低,除T1组外余各组与对照组相比差异均有显著性(P0.05),但脑组织内胆红素含量、Na+ K+ ATPase活力除T1组外各组4 h,8 h之间差异有显著性(P0.05),脑组织内胆红素含量与Na+ K+ ATPase活力呈负相关(r=-0.86,P<0.01)。结论：脑组织内胆红素对Na+ K+ ATPase活力有抑制作用。     

Cellular response to renal hypoxia is different in adolescent and infant rats

Immature renal tubules are more tolerant to ischemia than mature renal tubules. Here we compared the developmental pattern for some cellular responses evoked by hypoxia and reoxygenation in renal proximal tubules from 10- and 40-day-old rats. Redistribution of Na(+)-K(+)-ATPase from the plasma membrane was studied by confocal microscopy techniques in primary cultured renal proximal tubular cells. The developmental expression of Na(+)-K(+)-ATPase, micro-calpain and heme oxygenase-1 was measured by RT-PCR techniques in rat renal cortex. In response to hypoxia Na(+)-K(+)-ATPase redistribution from the plasma membrane was almost 2-fold increased in cells isolated from mature kidneys compared with cells isolated from immature kidneys. Reoxygenation resulted in a complete reestablishment of Na(+)-K(+)-ATPase in the plasma membrane in the immature but not in the mature cells. The dissociation of Na(+)-K(+)-ATPase from the plasma membrane was associated with a reduced activity and a reduced expression of Na(+)-K(+)-ATPase in the mature but not in the immature tubular cells. The expression of micro-calpain, a factor shown to induce ischemic injury to proximal tubular cells, was significantly lower in the immature compared with the mature kidney, whereas the expression of heme oxygenase-1, a factor shown to protect from renal ischemic injury, was significantly higher in the immature kidney. The results help to explain the increased tolerance of the immature kidney to injury caused by ischemia and reperfusion.     

Regional cerebral Na+K+ ATPase activity following octanoate administration

Sodium octanoate in an 0.2 M solution was administered to rabbits by continuous slow IV infusion over 4 hr. Controls were given identical infusions of normal saline. The animals were then sacrificed, brains were removed, and specific areas were isolated and assayed for Na+K+ ATPase activity. Significant inhibition of regional Na+K+ ATPase activity was detected in cortex, thalamus, hypothalamus, pons, and medulla of rabbits given octanoate when compared to controls.     

Calcium and sodium transport processes in patients with cystic fibrosis. I. A specific decrease in Mg2+-dependent, Ca2+-adenosine triphosphatase activity in erythrocyte membranes from cystic fibrosis patients.

Calcium-ATPase activity (Mg2+-dependent Ca2+-ATPase, ATP phosphohydrolase, EC 3.6.1.3) in erythrocyte membrane preparations from cystic fibrosis (CF) patients was greatly reduced compared to erythrocyte membranes from control subjects. The Km for calcium was found to be similar in the two groups; however, the Vmax, the maximal rate of activation of the Ca2+-ATPase, is reduced by 50% in the erythrocyte membrane preparations of the CF patients (P less than 0.001). In contrast, the Mg2+-ATPase activity of erythrocyte membranes from CF patients was unchanged compared to the control subjects. No difference in the Na+,K+-ATPase activity in erythrocyte membranes from CF patients compared to control patients could be observed. This indicates that the Ca2+-ATPase activity noted in CF erythrocytes is not part of a generalized membrane or membrane-bound enzyme alteration. It remains to be determined whether this alteration in Ca2+-ATPase activity is directly related to a defect in calcium transport in these cells and is a generalized phenomenon in CF present in cell types more directly involved in secretion.     

Effect of cortisone on postnatal development of ion transport in rabbit small intestine

To study the effect of corticosteroids on postnatal maturation of Na+ transport in the small intestine, we studied 10-12-day-old suckling rabbits after they had received cortisone acetate, 20 mg/kg SC on days 3, 4, and 5 of life. When killed, the cortisone-injected animals weighed significantly less than saline-injected controls. In jejunal villus enterocytes isolated from this cortisone-treated group, the specific activities of sucrase and Na+-K+-ATPase were significantly greater than those in control enterocytes. Studied in Using chambers, a significant electrical and ion-flux response to glucose was observed in the jejunal epithelium of the treated group, but not in controls. We conclude that exogenous cortisone, administered early in life, can stimulate the precocious development not only of certain epithelial enzymes but also glucose-facilitated Na+ transport in the jejunum of the rabbit.     

Altered erythrocyte sodium-lithium counter-transport and Na+/K+-ATPase activity in cystic fibrosis

Patients with cystic fibrosis (CF) exhibit normal concentrations of sodium and chloride in spite of the disturbance of Cl^- and Na+ transport in epithelial cells. To characterize compensatory mechanisms in the regulation of sodium homeostasis, erythrocytes of 13 CF patients were analysed for sodium-lithium counter-transport (SLC), Na+/K+ -ATPase activity and intracellular sodium content. Values were compared to those of healthy controls. Patients with CF had normal serum sodium and chloride concentrations and renal excretions of these ions were within the physiological range. Intracellular sodium concentration was similar in the CF and the control group (6.8 ± 2.2 vs 5.7 ± 1.0 mmol/l RBCs). Red blood cells' SLC and Na+/ K+ -ATPase activity were elevated in CF patients (381 ± 106 μmol/h/l RBCs vs 281 ± 64; p < 0.01) and (445 ± 129 μmol ATP mg prot/h vs 322 ± 84, p < 0.01). Our study demonstrates that transmembrane cation transport systems are highly activated in CF. The increased sodium transport may be part of a compensatory mechanism of sodium homeostasis in children with CF.     

Calcium-ATPase activity in cystic fibrosis erythrocyte membranes: decreased activity in patients with pancreatic insufficiency

The activity of Ca-ATPase (Ca2+,Mg2+-ATPase, ATP phosphohydrolase, EC 3.6.1.3) was measured in erythrocyte membrane preparations from 37 cystic fibrosis patients, 27 with pancreatic insufficiency and 10 with pancreatic sufficiency, and from 24 healthy controls. The mean maximal calcium-stimulated specific activities, in the absence and presence of purified calmodulin, of the pancreatic sufficient patients (34.3 +/- 4.2 and 75.9 +/- 6.9 nmol/min/mg) was indistinguishable from that of controls (35.8 +/- 2.6 and 84.3 +/- 4.7 nmol/min/mg), while both activities of patients with pancreatic insufficiency were significantly decreased (28.9 +/- 1.3, p less than 0.02; 65.2 +/- 3.0, p less than 0.001) compared to the control group. Similarly, the mean erythrocyte membrane (Na + K)ATPase activity was decreased only for those patients with a history of steatorrhea and who clinically required pancreatic enzyme therapy and had low immunoreactive trypsin levels (10.6 +/- 0.8 versus control, 13.4 +/- 1.1, and pancreatic sufficient patients, 13.3 +/- 1.4 nmol/min/mg; p less than 0.025). No correlation was found between any of the ATPase activities and the clinical scores of the patients, suggesting the lack of significant contribution of general clinical status to the activities of those cation transporters.