耐力训练和急性力竭运行对大鼠组织金属硫蛋白含量的不同…

为探讨金属硫蛋白（ＭＴ）在运动提高机体自我贩作用,本文实验观察了游泳运动对大鼠心、肝、肺、脑、血管、因浆和骨骼肌等组织金属硫蛋白含量的影响。结果表明耐力训练组大鼠心、肝、肺和骨骼组织金属硫蛋白含量较政党对照组明显降低１３－３４％（Ｐ〈０．０５）;急性力竭运动组大鼠心、肝、脑、肺和骨骼肌组织其含量较正常对照则明显或高２１－７５％（Ｐ〈０．０５）;但两组大鼠血管和血浆ＭＴ含量变化与对照组大鼠要比无统计     

Cardiac adaptation to endurance exercise in rats

Endurance exercise is widely assumed to improve cardiac function in humans. This project has determined cardiac function following endurance exercise for 6 (n = 30) or 12 (n = 25) weeks in male Wistar rats (8 weeks old). The exercise protocol was 30 min/day at 0.8 km/h for 5 days/week with an endurance test on the 6th day by running at 1.2 km/h until exhaustion. Exercise endurance increased by 318% after 6 weeks and 609% after 12 weeks. Heart weight/kg body weight increased by 10.2% after 6 weeks and 24.1% after 12 weeks. Echocardiography after 12 weeks showed increases in left ventricular internal diameter in diastole (6.39 ± 0.32 to 7.90 ± 0.17 mm), systolic volume (49 ± 7 to 83 ± 11 μl) and cardiac output (75 ± 3 to 107 ± 8 ml/min) but not left wall thickness in diastole (1.74 ± 0.07 to 1.80 ± 0.06 mm). Isolated Langendorff hearts from trained rats displayed decreased left ventricular myocardial stiffness (22 ± 1.1 to 19.1 ± 0.3) and reduced purine efflux during pacing-induced workload increases. 31P-NMR spectroscopy in isolated hearts from trained rats showed decreased PCr and PCr/ATP ratios with increased creatine, AMP and ADP concentrations. Thus, this endurance exercise protocol resulted in physiological hypertrophy while maintaining or improving cardiac function. (Mol Cell Biochem 251: 51–59, 2003)     

The localization of mercury and metallothionein in the cerebellum of rats experimentally exposed to methylmercury

Summary Rats were dosed with methylmercuric chloride, either by gastric gavage (5 × 10 mg kg^-1 body weight over a 15-day period), or in their drinking water (20 mg methylmercuric chloride l^–1 for 14 or 42 days). Localization of mercury within the cerebellum was performed with a silver physical development technique, and metallothionein with dinitrophenyl hapten-sandwich immunohistochemistry. Mercury was detected in structurally undamaged Purkinje neurones and adjacent Bergmann glial cells; no mercury was detected in granule cells even though these small cells nearest the Purkinje layer had a high incidence of pyknotic nuclei. In general, metallothionein was detected mainly in Bergmann glial cells, Purkinje cells, astrocytes and glial cells of white matter; no metallothionein was detected in granule cells. We hypothesized that the resistance of Purkinje cells to methylmercuric chloride reflects their ability to transform organic mercurials to inorganic mercury that, in turn, induces the synthesis of radical-scavenging metallothionein molecules.     

Adaptations to a high-fat diet that increase exercise endurance in male rats

Eighty-seven male Sprague-Dawley rats (245-300 g) were randomly assigned to one of two experimental groups. The first group consumed a diet high in fat and low in carbohydrate (LCD), whereas the second group ate a normal diet (ND). After either 1 or 5 wk on the diets, rats from each group were killed either before or after an exhausting run on a rodent treadmill (35 m X min-1, 0% grade). The LCD animals ran significantly longer before exhaustion at both week 1 (44.9 +/- 5.1 vs. 41.6 +/- 4.2 min) and week 5 (47.1 +/- 3.6 vs. 35.5 +/- 3.1 min) (P less than 0.05). Adaptations to the LCD included lower muscle and liver glycogen content, decreased rate of glycogen breakdown during exercise, decreased lactate production, and elevated blood ketone levels. In addition to these substrate changes, the LCD caused increased enzyme activities of muscular 3-hydroxyacyl-CoA dehydrogenase (35-110%) and citrate synthase (15-20%). These data indicate that rats exposed to a high-fat diet are capable of prolonged intense exercise in spite of limited glycogen stores. This improved capacity for exercise appears to be partially the result of muscular adaptations to the diet, which apparently increase the ability to oxidize fat and concomitantly spare glycogen.     

Effect of cocaine on exercise endurance and glycogen use in rats

To determine the effects of cocaine on exercise endurance, male rats were injected intraperitoneally with cocaine (20 mg/kg body wt) or saline and then run to exhaustion 20 min later at 22 m/min and 15% grade. Saline-injected animals ran 74.9 +/- 16.5 (SD) min, whereas cocaine-treated rats ran only 29 +/- 11.6 min. The drug had no effect on resting blood glucose or lactate levels, nor did it affect resting glycogen levels in liver or red and white vastus muscle. However, it did reduce resting soleus glycogen content by 30%. During exercise liver and soleus glycogen depletion occurred at the same rate in saline- and cocaine-treated animals. In contrast, the rate of glycogen depletion during exercise in red and white vastus was markedly increased in cocaine-treated rats with a corresponding elevation in blood lactate (12 vs. only 5 mM in saline group) at exhaustion. These data suggest that cocaine administration (20 mg/kg) before submaximal exercise dramatically alters glycogen metabolism during exercise, and this effect has a negative impact on exercise endurance.     

Changes of renal function and structure in rats exposed to cold

The kidney appears to play a crucial role in both initiating and maintaining the high blood pressure in cold-induced hypertension (CIH). The aim of the present study was to evaluate the changes of renal function and structure in rats exposed to cold for 2, 4 and 6 weeks. Systolic blood pressure increased significantly after 2 weeks of cold exposure and was maintained throughout the whole experiment. Upregulation of angiotensin type 1 receptor (AT₁R) expression was seen in the vascular zone and distal tubule after 4 and 6 weeks of cold exposure. This was accompanied by an increase in malondialdehyde (MDA) levels and decreases in superoxide dismutase (SOD), nitric oxide synthase (NOS) activities and nitric oxide (NO) content in kidney. Structural changes were also observed in glomeruli, tubules and arteries in cold-treated rats. These results suggest that upregulation of kidney AT₁R plays a critical role in the development of CIH, and its interaction with oxidative stress, NO and NOS may be involved in changes of renal function and structure.     

Hydrogen improves exercise endurance in rats by promoting mitochondrial biogenesis

BackgroundPrevious studies have shown that hydrogen water has antioxidant and anti-inflammatory effects on exercise-induced fatigue; however, its molecular mechanism remains unclear.MethodsAdult male Sprague-Dawley rats were randomly divided into a pure water drinking group (NC) and a hydrogen water drinking group (HW) (n = 7), and 2-week treadmill training was used to establish a sports model. Gut bacterial community profiling was performed using 16S rRNA gene sequencing analysis. The expression levels of mitochondrial energy metabolism-related genes and the levels of sugar metabolites and enzymes were measured.ResultsThe exercise tolerance of rats in the HW group significantly improved, and the distribution and diversity of intestinal microbes were altered. Hydrogen significantly upregulated genes related to mitochondrial biogenesis, possibly via the Pparγ/Pgc-1α/Tfam pathway. In addition, hydrogen effectively mediated the reprogramming of skeletal muscle glucose metabolism.ConclusionOur findings establish a critical role for hydrogen in improving endurance exercise performance by promoting mitochondrial biogenesis via the Pparγ/Pgc-1α/Tfam pathway.     

Effect of endurance exercise training on muscle glycogen supercompensation in rats

Nakatani, Akira, Dong-Ho Han, Polly A. Hansen, Lorraine A. Nolte, Helen H. Host, Robert C. Hickner, and John O. Holloszy. Effect of endurance exercise training on muscle glycogensupercompensation in rats. J. Appl.Physiol. 82(2): 711-715, 1997.The purpose of this study was to test the hypothesis that the rate and extent ofglycogen supercompensation in skeletal muscle are increased byendurance exercise training. Rats were trained by using a 5-wk-long swimming program in which the duration of swimming was gradually increased to 6 h/day over 3 wk and then maintained at 6 h/day for anadditional 2 wk. Glycogen repletion was measured in trained anduntrained rats after a glycogen-depleting bout of exercise. The ratswere given a rodent chow diet plus 5% sucrose in their drinking waterad libitum during the recovery period. There were remarkabledifferences in both the rates of glycogen accumulation and the glycogenconcentrations attained in the two groups. The concentration ofglycogen in epitrochlearis muscle averaged 13.1 ± 0.9 mg/g wet wtin the untrained group and 31.7 ± 2.7 mg/g in the trained group(P < 0.001) 24 h after the exercise.This difference could not be explained by a training effect on glycogensynthase. The training induced ~50% increases in muscle GLUT-4glucose transporter protein and in hexokinase activity inepitrochlearis muscles. We conclude that endurance exercise trainingresults in increases in both the rate and magnitude of muscle glycogensupercompensation in rats.

     

Acetylcholine in the brain of rats exposed to acute irradiation

A two-fold increase in acetylcholine, that can randomly be released by brain synaptosomes, is registered 60 min following whole-body X-irradiation of rats with a dose of 0.21 C/kg; depolarization of the synaptosome membranes by potassium chloride increases the release of acetylcholine the augmentation of the release in this case being lower than that in the control. The initial rate of spontaneous neuromediator release from synaptosomes grows by 80 per cent whereas after depolarization of synaptosome membranes by potassium chloride, by 15 per cent. There is a 2.5-fold increase in the maximum rate of a highly specific uptake of choline with Km value being constant. Acetylcholine content of gray substance of irradiated rat brain is invariable.     

Selenium deficiency, endurance exercise capacity, and antioxidant status in rats

Increased O2 metabolism imposed by physical exercise is likely to augment the production of active O2 species that have been shown to react with lipids, proteins, and DNA. Antioxidants and antioxidant enzymes, such as the selenium enzyme glutathione peroxidase, minimize or prevent such potentially toxic reactions. This study shows that selenium deficiency decreases glutathione peroxidase activity in liver and muscle (less than 80%, P less than 0.001), increases total glutathione in liver, muscle, and plasma (P less than 0.05) and increases muscle cytochrome oxidase activity, and ubiquinone content (P less than 0.05) but has no effect on endurance capacity. Exercise to exhaustion resulted in a significant (P less than 0.001) elevation of total and oxidized glutathione (GSSG) and a significant (P less than 0.05) decrease of vitamin E in plasma of control and selenium-deficient rats. Acute exercise also increased tissue GSSG levels in both control and selenium-deficient groups of rats. Hence, despite a large depletion of selenium-deficient glutathione peroxidase, pronounced oxidation of glutathione to GSSG can be produced by the increased oxidative metabolism during physical exercise. The results suggest that the residual glutathione peroxidase activity is sufficient to detoxify hydroperoxides in exercising selenium-deficient animals and to prevent the impairment of endurance capacity.     

Effects of exogenous metallothionein on acute cadmium toxicity in rats

The present study was carried out to evaluate the effect of exogenously administered metallothionein (MT) to rats exposed to high cadmium levels. A total of 72 rats were used in the study. The animals were divided into three groups: controls, Cd administered, and Cd+MT. Cadmium was administered by subcutaneous injection of cadmium(II) chloride at a dose of 3.5 mg/kg for 7 d. In addition to CdCl₂, 30 μmol/kg MT was administered to the second group of rats (group II). Control rats received 0.5 mL physiologic serum via subcutaneous injection. Eight rats from each group were sacrificed on the 1st, 3rd, 5th, and 7th day after administration of the compounds. Liver, kidney, and blood samples were harvested. Levels of malondialdehyde (MDA), glutathione peroxidase (GSH-Px), serum ALT, AST, BUN, ALP, creatinine, and urea were measured. MDA levels in group I were observed to increase starting from d 1 compared to group II (p<0.05). Although MDA levels in group II were higher than controls (p<0.05), they were lower, especially in liver and blood, compared to group II. Erythrocyte GSH-Px activity levels were determined to decrease starting from d 1 in both groups (p<0.05). Decreases in GSH-Px activity levels in group II were less than group I. Serum creatinine levels in both groups were increased significantly compared to controls (p<0.05); the increase in group I was higher than group II. Serum ALT, AST, and ALP levels in group I increased to very high levels compared to controls, whereas increases in group II were at moderate levels (p<0.05). Although serum BUN levels were determined to be reduced, there was no significant change among the groups. Serum urea levels in both groups were higher than controls. Based on our results, it is possible to postulate that exogenous MT can act as antioxidant against Cd toxicity and lipid peroxidation.     

Expression of Bcl-2 and Bax in mouse renal tubules during kidney development

Bcl-2 and Bax play an important role in apoptosis regulation, as well as in cell adhesion and migration during kidney morphogenesis, which is structurally and functionally related to mitochondria. In order to elucidate the role of Bcl-2 and Bax during kidney development, it is essential to establish the exact location of their expression in the kidney. The present study localized their expression during kidney development. Kidneys from embryonic (E) 16-, 17-, 18-day-old mouse fetuses, and postnatal (P) 1-, 3-, 5-, 7-, 14-, 21-day-old pups were embedded in Epon. Semi-thin serial sections from two E17 kidneys underwent computer assisted 3D tubule tracing. The tracing was combined with a newly developed immunohistochemical technique, which enables immunohistochemistry on glutaraldehyde fixated plastic embedded sections. Thereby, the microstructure could be described in detail, and the immunochemistry can be performed using exactly the same sections. The study showed that Bcl-2 and Bax were strongly expressed in mature proximal convoluted tubules at all time points, less strongly expressed in proximal straight tubules, and only weakly in immature proximal tubules and distal tubules. No expression was detected in ureteric bud and other earlier developing structures, such as comma bodies, S shaped bodies, glomeruli, etc. Tubules expressing Bcl-2 only were occasionally observed. The present study showed that, during kidney development, Bcl-2 and Bax are expressed differently in the proximal and distal tubules, although these two tubule segments are almost equally equipped with mitochondria. The functional significance of the different expression of Bcl-2 and Bax in proximal and distal tubules is unknown. However, the findings of the present study suggest that the mitochondrial function differs between mature proximal tubules and in the rest of the tubules. The function of Bcl-2 and Bax during tubulogenesis still needs to be investigated.     

Mercury distribution and renal metallothionein induction after subchronic oral exposure in rats

The effects of long-term daily intake of low and high levels of mercury on its organ distribution and binding to renal metallothionein (MT) in male rats were studied. The animals were exposed to mercuric chloride labelled with²⁰³Hg via drinking water for 8 weeks (5, 50 and 500 m Hg). The greatest concentration of mercury was found in the kidneys. Similar levels of radioactivity in the buccal cavity and oesophagus were also observed by whole-body autoradiography. In the kidneys, the mercury was accumulated in the outer stripe of the outer zone of the medulla and, to a minor degree, in the renal cortex. Almost 50% the total renal mercury was associated to MT. The binding capacity of the renal MT for mercury tends to saturate with increasing doses, thus this means that the capacity of the kidneys to accumulate mercury is limited.     

Evidence for a decreased membrane recycling in the cells of renal proximal tubules exposed to high concentrations of ferritin

Summary The present study was performed to investigate whether membrane recycling via the dense apical tubules in cells of renal proximal tubules could be modified after exposure to large amounts of cationized ferritin. Proximal tubules in the rat kidney were microinfused in vivo with cationized ferritin for 10 or 30 min and then fixed with glutaraldehyde by microinfusion, or proximal tubules were microinfused with ferritin for 30 min and then fixed 2 h thereafter. The tubules were processed for electron microscopy, and the surface density and the volume density of the different cell organelles involved in endocytosis were determined by morphometry. The morphometric analyses showed that after loading of the endocytic vesicles with ferritin the surface density of dense apical tubules decreased to about 50% of the original value. However, 2 h later when ferritin had accumulated in the lysosomes the surface density of dense apical tubules had returned to control values. Furthermore, cationized ferritin was virtually absent from the Golgi region, indicating that the Golgi apparatus in these cells does not participate in membrane recycling. In conclusion, the present study shows that membrane recycling in renal proximal tubule cells can in part be inhibited by loading the endocytic vacuoles with ferritin.