Testing the compatibility of a combination of tiamulin/chlortetracycline 1:3 premix (Tetramutin-Novartis) given in feed at different levels with salinomycin in chickens

The compatibility of salinomycin (SA) (60 mg/kg feed) and Tetramutin (TM), a combination of tiamulin (TI) and chlortetracycline (CTC) in a 1:3 ratio, included in varying concentrations, was tested in broiler chickens. Assessment was based on clinical signs, body weight gain, feed conversion efficiency, gross pathological lesions and histological lesions in liver, heart and pectoral muscles, as well as analysis of blood for lactate dehydrogenase (LDH), aspartate dehydrogenase (AST) and creatine phosphokinase (CPK) activity. It was shown that chickens can be safely treated in feed for 7 days with TM containing TI concentrations of 33 or 55mg/kg feed together with SA at 60mg/kg. However, higher levels of TI (100 and 150 mg/kg feed) caused some adverse effects. There was no mortality but there was mild depression, 'leg weakness' accompanied by specific histological lesions in pectoral muscles (obliteration of cross-striation and swelling of muscle fibres, nuclei of muscle cells, hyalinization and destruction of sarcoplasm), a mild increase of AST activity, and a significant increase of CPK and LDH activity in blood. These latter two parameters can be used as an early indication of TI and SA incompatibility.     

Evaluation of tiamulin and lincomycin for the treatment of broiler breeders experimentally infected with the intestinal spirochaete Brachyspira pilosicoli

Brachyspira pilosicoli strain CPSp1 isolated from a chicken in a broiler breeder flock in Queensland was used to experimentally infect 30 individually caged 22-week-old Cobb 500 broiler breeder hens. Another 10 birds were sham-inoculated with sterile broth. All birds failed to become colonized. At 29 weeks of age, all birds were transferred to a diet containing 50 parts/10 6 zinc bacitracin (ZnB) and were re-challenged with the same B. pilosicoli strain at 32 weeks of age, weekly for 5 weeks. The majority of the inoculated birds then became colonized, confirming previous findings that ZnB can increase susceptibility to colonization with B. pilosicoli. The control group remained uninfected. Infected groups tended to have an increased faecal water content and faecal staining of eggshells. Ten birds were then treated by crop tube with 25 mg/kg body weight tiamulin for 5 days, and 10 birds with 20 mg/kg body weight lincomycin for 5 days. Both treatments removed the infection, while untreated birds remained infected. The results support previous observations that ZnB at 50 parts/10 6 in the diet increases the susceptibility of birds to B. pilosicoli infection, and demonstrated the usefulness of both tiamulin and lincomycin for treatment of infection with B. pilosicoli in adult birds.     

Resistance to anticoccidial drugs of Dutch avian Eimeria spp. field isolates originating from 1996, 1999 and 2001

Fifteen Eimeria spp. field isolates sampled on Dutch broiler farms were subjected to an Anticoccidial Sensitivity Test (AST) in a battery cage study. Four isolates dated from 1996, another four from 1999 and the last seven isolates from 2001. The selected anticoccidial drugs were monensin, narasin, salinomycin, lasalocid, nicarbazin, diclazuril, halofuginone, maduramicin and meticlorpindol/methylbenzoquate. Maduramicin and halofuginone were not included in the ASTs of 1999 and 2001, while meticlorpindol/methylbenzoquate was not tested in 1996 and 1999. Eimeria acervulina present in each of the four 1996 field isolates showed resistance for almost all products tested except maduramicin (1/4) and salinomycin (1/4), which appeared to be reduced sensitive. In 1999 the same species presented a similar resistance pattern for most products, although reduced sensitivity occurred for salinomycin (1/4), and sensitivity was found for diclazuril (2/4), monensin (1/4) and narasin (1/4). In the year 2001 increased sensitivity to various products was found. Higher sensitivity was found for meticlorpindol/methylbenzoquate (7/7) and salinomycin and narasin (both 4/7), followed by nicarbazin (3/7) and monensin (2/7). Reduced sensitivity was found for monensin (3/7), lasalocid (2/7), salinomycin and narasin (1/7). E. maxima was only found in one field isolate per year. The E. maxima from 1996 was resistant to all products except narasin (sensitive) and halofuginone (reduced sensitive). In 1999 this species was reduced sensitive to narasin and lasalocid, showing resistance for the other products. The strain originating from the 2001 isolate was reduced sensitive to most products except monensin and narasin (resistant). Full sensitivity was found for meticlorpindol/methylbenzoquate. E. tenella was present in one isolate of 1996, two of 1999 and four isolates of 2001. The AST of 1996 showed reduced sensitivity for nicarbazin, and sensitive to narasin, maduramicin and halofuginone. All other products showed resistance. In 1999 both strains showed resistance to all products tested. For the year 2001 full sensitivity was found to meticlorpindol/methylbenzoquate. Sensitivity was also found for salinomycin (1/4), nicarbazin (2/4), diclazuril (2/4) and lasalocid (2/4), monensin (1/4) and narasin (1/4). Reduced sensitivity was found for nicarbazin (1/4), lasalocid (1/4) and narasin (1/4). The different resistance patterns of Dutch coccidiosis isolates and resistance of coccidia in general is discussed.     

Influence of in-feed zinc bacitracin and tiamulin treatment on experimental avian intestinal spirochaetosis caused by Brachyspira intermedia

Thirty individually caged layer hens were inoculated with Brachyspira intermedia , and 20 control birds remained unchallenged. Birds received a diet containing 100 parts/10 6 zinc bacitracin (ZnB), and were monitored for 10 weeks. B. intermedia was recovered sporadically from five of the inoculated birds, and there were no significant effects on body weight, faecal water or egg production. ZnB was presumed to be indirectly inhibiting spirochaete growth, and when removed from the diet, 18 of the 30 inoculated birds rapidly became culture positive. After 4 weeks, 10 of the 30 infected birds were treated with tiamulin at 25 mg/kg for 5 days, and 10 were returned to the diet containing ZnB. Birds receiving tiamulin became spirochaete negative and maintained their egg production, but re-infection occurred. The other 20 infected birds had a significant drop in egg production, but those receiving ZnB showed a reduced colonization by B. intermedia after 3 weeks.     

Histopathology of monensin-tiamulin myopathy in broiler chicks

Thirty-six 7-day-old broiler chicks were simultaneously given food containing monensin, and water containing tiamulin, both drugs being at normal levels of usage. Equal numbers of chicks on a basal diet and plain water served as the controls. Anorexia, depression, drowsiness, leg weakness and a decrease in body weight appeared on days 2 to 3 of administration in several treated chicks. These clinical signs and growth retardation were prevalent and severe on days 4 to 7, at which time some chicks became recumbent. From day 9, chicks showed gradual recovery from the clinical signs and growth retardation. Histopathologically, the neck and leg skeletal muscles examined were severely affected in treated chicks, but cardiac and pectoral muscles were intact. Besides hyalinisation and floccular change which appeared infrequently in early stage of the experiment, muscle fibres showing an enlargement of the nuclei and a distention of a pale to basophilic sarcoplasm, suggestive of partial myofibrillar lysis and subsequent reparative change, dominated all affected muscles. These degenerative and reparative changes were considered to be distinctive for monensin-tiamulin myopathy in chicks.     

Intracellular IL-10 detection in T cells by flowcytometry: the use of protein transport inhibitors revisited

In the past two decades, interleukin-10 (IL-10) has gained much attention as an important regulatory cytokine involved in self-tolerance. Functional assessment of IL-10 producing immune cells is traditionally done by stimulation and measurement of cytokine production by flowcytometry. Thereby a protein transport inhibitor like monensin is used to accumulate the cytokine of interest intracellularly. In this study we elaborated on the monensin effect on cytokine detection and focused on IL-10 detection in human T cells. Peripheral blood mononuclear cells (PBMC) of 32 study subjects were isolated and stimulated with PMA/ionomycin, in the absence and presence of monensin, and stained intracellularly for IFN-γ, IL-4, IL-10 and IL-17A. Our results re-established that detection of IFN-γ+ and IL-4+ T cells benefited from the presence of monensin during stimulation. However, stimulation in the presence of monensin yielded lower proportions of IL-10+ T cells (0.45% (0.28-0.80) versus 0.80% (0.50-1.50) of CD4+ T cells, p<0.01), although monensin addition did result in an increased MFI (2431 (1273-4959) versus 1928 (1147-3760), p<0.01). Detectable fractions of IL-17A+ CD4+ T cells were not affected by monensin. A shorter incubation time, but not lower monensin concentrations, was effective in improving the detection of IL-10+ T cells. We found a strong correlation between the fraction of IL-10+ CD4+ T cells in the presence and absence of monensin (R=0.80 p<0.01). Next to this, also the detection of IL-10+ NK-T cells and IL-10+ monocytes, but not IL-10+ B cells, is impaired in the presence of monensin. This study shows that the effect of monensin on cytokine accumulation is time and cytokine dependent. Due to the use of monensin, previous research may have underestimated the number of IL-10+ leukocytes or may even have not been able to detect them at all. It is important to consider this for future research or when interpreting historical IL-10 data.     

Ultrastructure of mouse striated muscle fibers following pravastatin administration

To examine the effect of pravastatin administration on striated muscle ultrastructure, 10 BalbC mice were given pravastatin 40 mg/kg/day for 3 weeks. At the end of the study, blood was withdrawn for evaluation of the serum creatine phospho-kinase (CPK) level and the muscles of the hind legs, as well as the heart and liver of the animals were examined with a light and transmission electron microscope. After treatment with pravastatin the results showed a 101% increase in serum CPK level in comparison to untreated controls. Hematoxillin-eosin stained tissues of pravastatin treated mice did not show any abnormal findings. While the ultrastructure of the heart and liver of the treated animals appeared normal, the muscle fibers showed a marked alterations of the mitochondria, which were increased in size compared to those of the controls. The cristae were heavily damaged and even completely destructed, giving the mitochondria appearance of empty vacuoles. The findings are in favor of a specificity of pravastatin for striated muscles. This revised version was published online in July 2006 with corrections to the Cover Date.     

Function and distribution of beta3-adrenoceptors in rat, rabbit and human urinary bladder and external urethral sphincter.

1. Activation of beta-adrenoceptors causes relaxation of the urinary bladder and contraction of the external urethral sphincter, which consists of fast-contracting skeletal muscles. A beta2-adrenoceptor agonist, clenbuterol, recently has been developed as a therapeutic drug for the treatment of urinary incontinence, however beta2-adrenoceptor agonists have undesirable effects on cardiac and striated muscle function. 2. In this study, we compared the effects of the beta2-adrenoceptor agonist, clenbuterol and of a novel beta3-adrenoceptor agonist, GS332, on urinary bladder and external urethral sphincter function in rat, rabbit and human. We also determined the distribution of beta3-adrenoceptors in human urinary bladder and external urethral sphincter, using radioligand-binding techniques. 3. Clenbuterol induced marked relaxations in rat, rabbit and human urinary bladder smooth muscles and also induced marked contractions in rat periurethral striated muscles (external urethral sphincter), while GS332 induced marked relaxations in rat and human, but not in rabbit, urinary bladder smooth muscles and induced small contractions in rat periurethral striated muscles. 4. The radioligand binding studies showed presence of beta2- and beta3-adrenoceptors in human urinary bladder, external urethral sphincter and abdominal rectus muscles. The affinities of GS332 were the highest in urinary bladder and the lowest in the skeletal (abdominal rectus) muscles, while the affinities of clenbuterol were similar in urinary bladder, external urethral sphincter and the skeletal (abdominal rectus) muscles. 5. These results suggest that GS332 could, similarly clenbuterol, have a role in the treatment of urinary frequency and urinary incontinence.     

The Distribution of Muscles Fibers and Their Types in the Female Rat Urethra: Cytoarchitecture and Three‐Dimensional Reconstruction

An attempt to explore urethral cytoarchitecture including the distribution of smooth muscles and fast and slow striated muscles of adult female Sprague Dawley rat—a popular model in studying lower urinary tract function. Histological and immunohistochemical stainings were carried out to investigate the distribution of urethral muscle fibers and motor end plates. The urethral sphincter was furthermore three‐dimensionally reconstructed from serial histological sections. The mucosa at the distal urethra was significantly thicker than that of other segments. A prominent inner longitudinal and outer circular layer of smooth muscles covered the proximal end of urethra. Thick circular smooth muscles of the bladder neck region (urethral portion) decreased significantly distalward and longitudinal smooth muscles became 2‐ to 3‐fold thicker in the rest of the urethra. An additional layer of striated muscles appeared externally after neck region (urethra) and in association with motor end plates ran throughout the remaining urethra as the striated sphincter layer. Most striated muscles were fast fibers while relatively fewer slow fibers often concentrated at the periphery. A pair of extraneous striated muscles, resembling the human urethrovaginal sphincter muscles, connected both sides of mainly the distal vagina to the dorsal striated muscles in the wall of the middle urethra. The tension provided by this pair of muscles, and in conjunction with the striated sphincter of the urethral wall, was likely to function to suspend the middle urethra and facilitates its closure. Comprehensive morphological data of urethral sphincter offers solid basis for researchers conducting studies on dysfunction of bladder outlet. Anat Rec, 296:1640–1649, 2013. © 2013 Wiley Periodicals, Inc.     

Parameters for quantification of hunger in broiler breeders

The commercial restricted feeding programme of broiler breeders has a major negative effect on welfare, as the birds are continuously hungry. Objective parameters of hunger are needed to evaluate new management or feeding systems that may alleviate hunger and thus improve broiler breeder welfare. The aim of this experiment was to develop such parameters. Female broiler breeders (Hybro G), n=10 per treatment, were subjected to different levels of feed restriction and we assumed that we thus induced different levels of hunger. Treatment groups were fed ad libitum and at 90%, 70%, 50%, 35% and 25% of ad libitum. In addition, female broiler breeders that were less intensively selected on growth and food conversion (JA57, n=10 per treatment) were fed ad libitum and at 70% of ad libitum. At 6-7 weeks of age, home pen behaviour, behaviour in the open field and baseline plasma corticosterone, glucose and nonesterified fatty acid (NEFA) concentrations were determined. Thereafter, birds were subjected to the feed intake motivation (FIM) test that measures compensatory feed intake. Linear relationships between the level of restriction and the compensatory feed intake on the first days of the FIM test and the glucose/NEFA ratio were found which indicate that these parameters can be used to quantify the level of hunger. Curvilinear relationships between sitting and standing in the home pen, walking in the open field and level of restriction were found. A third-grade hyperbolic relationship between the level of restriction and the baseline plasma corticosterone concentration was found. Thus, these parameters do not seem to represent a straightforward relation with the level of hunger. Intensive selection on growth and food conversion seems to have affected the behaviour but not the physiological responses to feed restriction, because the JA57 birds responded behaviourally, but not physiologically, different to feed restriction as compared with the Hybro birds.     

Anatomical and physiological characteristics of perineal muscles in the female rabbit

Little information is available on the participation of the perineal striated muscles in female reproductive processes. Here, we describe the gross anatomy and innervation of two striated perineal muscles in the female rabbit, the bulbospongiosus (BSM) and ischiocavernosus (ISM), and analyze their reflex electromyographic (EMG) activity in response to stimulation of the perigenital skin and vaginal tract. Twenty-four mature chinchilla-breed rabbit does were used: 12 to describe the anatomy and innervation of the muscles, 9 to determine reflex EMG activity of the muscles in response to stimulation of the perigenital skin and specific levels of the vaginal tract and 3 to analyze the effect of contraction of the muscles on intravaginal pressure. Both muscles were well developed, with their fibers originating at the ischiadic arch and inserting onto the ligamentum suspensorium clitoridis. Branches of the clitoral and perineal nerves innervated the BSM and ISM, respectively. Bilateral electrical stimulation of these nerves provoked retraction of the clitoral sheath and an increase in intravaginal pressure at the level of the perineal vagina. Whereas neither muscle responded to stimulation of the perigenital skin, both were reflexively activated during mechanical stimulation of the inner walls of the perineal vagina. Prolonged cervical stimulation inhibited this reflex. Thus, in reproductive processes such as copulation and/or parturition, the contraction of these muscles may be induced during stimulation of the perineal vagina.     

The infectivity of Eimeria sporozoites recovered from monensin medicated chickens

Sporozoites of embryo-adapted lines of Eimeria tenella, E. brunetti and E. necatrix were recovered from monensin medicated chickens. The viability of these sporozoites was compared with that of sporozoites recovered from unmedicated birds by assessing their infectivity in chicken embryos. Sporozoites of the three species of Eimeria recovered from 100 parts/10(6) monensin-medicated birds produced infections in embryos which were 94 to 98% less severe than infections resulting from the inoculation of sporozoites recovered from unmedicated chickens. A concomitant scanning electron microscope study revealed no apparent ultrastructural damage to the exposed sporozoites. Timed medication experiments in chickens showed that medication with monensin for the period covering sporozoite penetration in vivo was almost completely effective, being comparable to continuous medication. Medication started before infection (to ensure tissue concentrations of monensin) but terminating 5 to 7 hours before the oocysts were inoculated was ineffective.     

Synergistic effect of a combination of nicarbazin and monensin against coccidiosis in the chicken caused by Eimeria spp.

ABSTRACT

A clinical study was made into the abilities of nicarbazin and monensin and a nicarbazin?+?monensin combination to control Eimeria acervulina, E. maxima, and E. tenella in chickens. When included in the feed, at concentrations of 40?ppm nicarbazin or 40?ppm monensin, these products showed partial efficacy evaluated by daily weight gain (DWG) but no activity judged by daily feed intake (DFI) or feed conversion ratio (FCR). By contrast, the combination of 40?ppm nicarbazin?+?40?ppm monensin provided complete control of infection judged by greater DWG and DFI, and lower FCR. Monensin at a concentration of 40?ppm was ineffective in preventing lesions caused by all three species. Nicarbazin at a concentration of 40?ppm was unable to suppress lesions of E. acervulina and E. maxima but was able to suppress lesions caused by E. tenella. Nicarbazin 40?ppm?+?monensin 40?ppm suppressed lesions of all three species.

RESEARCH HIGHLIGHTS

• Nicarbazin or monensin at 40 ppm gave only partial control of Eimeria spp.

• A combination of 40 ppm nicarbazin + 40 ppm monensin controlled DWG, DFI and FCR.

• Nicarbazin or monensin at 40 ppm did not suppress all Eimeria spp. lesions.

• Nicarbazin 40 ppm + monensin 40 ppm suppressed lesions of all three species.

     

P物质阳性神经纤维对球海绵体肌和坐骨海绵体肌运动神经元的支配——HRP逆行示踪与免疫细胞化学研究

本研究应用 HRP逆行示踪与免疫细胞化学相结合的双重反应技术观察了 P物质纤维与前角躯体运动神经元的关系。用 WGA-HRP经大鼠球海绵体肌和坐骨海绵体肌注射后 ,逆行示踪标记的运动神经元分布于 L5 和 L6脊髓前角的背内侧核和背外侧核内侧部。 SP能纤维广泛分布于脊髓灰质 ,其中以后角最为密集。光镜下可见在前角的背内侧核和背外侧核内 ,SP阳性纤维呈点状和带有钮扣状膨大的纤维分布于逆行标记的运动神经元周围。电镜下可见 SP阳性纤维终末含有少量的大型囊泡和多量的清亮小泡。常见 SP阳性纤维末梢与 HRP逆行标记的运动神经元有紧密联系 ,并证明二者形成突触结构。本研究首次证实脑下行 P物质阳性纤维对调控球海绵体肌和坐骨海绵体肌运动神经元有直接支配关系 ,提示 P物质能纤维参与阴茎勃起和射精过程     

The effect of commonly used anticoccidials and antibiotics in a subclinical necrotic enteritis model

Necrotic enteritis poses an important health risk to broilers. The ionophore anticoccidials lasalocid, salinomycin, maduramicin, narasin and a combination of narasin and nicarbazin were tested in feed for their prophylactic effect on the incidence of necrotic enteritis in a subclinical experimental infection model that uses coccidia as a predisposing factor. In addition, drinking water medication with the antibiotics amoxicillin, tylosin and lincomycin was evaluated as curative treatment in the same experimental model. The minimal inhibitory concentrations (MICs) of all antibiotics and anticoccidials were determined in vitro against 51 Clostridium perfringens strains isolated from broilers. The strains examined appeared uniformly susceptible to lasalocid, maduramicin, narasin, salinomycin, amoxicillin and tylosin, whereas an extended frequency distribution range of MICs for lincomycin was seen, indicating acquired resistance in 36 isolates in the higher range of MICs. Nicarbazin did not inhibit the in vitro growth of the C. perfringens strains even at a concentration of 128 µg/ml. Supplementation of the diet from day 1 onwards with lasalocid, salinomycin, narasin or maduramicin led to a reduction in birds with necrotic enteritis lesions as compared with the non-medicated infected control group. A combination product of narasin and nicarbazin had no significant protective effect. Treatment with amoxicillin, lincomycin and tylosin completely stopped the development of necrotic lesions.     

Relationship between serum cholinesterase level and urinary bladder activity in patients with or without overactive bladder and/or neurogenic bladder

We compared the serum cholinesterase (ChE) level and various parameters between patients with or without overactive bladder (OAB) and/or neurogenic bladder (NB). A total of 258 patients who met the following criteria were enrolled: the presence/absence of OAB and/or NB was documented, laboratory data were available, and liver and renal functions were normal. Patients were divided into the 3 groups: 1) a NB+/OAB+ group who had both NB and OAB, 2) a NB-/OAB+ group who had OAB alone, and 3) an OAB- group who did not have OAB. The relationship between the presence of OAB and various biochemical parameters were examined, as well as the therapeutic outcome in relation to the same biochemical parameters. Forty-three patients had both NB and OAB (NB+/OAB+), 66 patients had OAB without NB (NB-/OAB+), and 149 patients had no OAB (OAB-). Serum ChE, total protein, and albumin levels were lower in the NB-/OAB+ group than the NB+/OAB+ group or the OAB- group. In the NB-/OAB+ group, a higher serum albumin or ChE level was associated with a better therapeutic outcome. These results suggest that a decrease of serum ChE level is related to the occurrence of OAB and the poor response to treatment in OAB patients without NB.     

Dihydropyridine receptor isoform expression in adult rat skeletal muscle

 The expression of isoform-specific dihydropyridine receptor Ca²⁺ channel (DHPR) α1-subunit genes in rat diaphragm, soleus and extensor digitorum longus muscles was investigated using RNase protection assays. As expected, mRNA expression levels for the DHPR skeletal muscle isoform were highest in extensor digitorum longus. Unexpectedly, both diaphragm and soleus expressed mRNA for the cardiac isoform at a significant level. Moreover, immunohistochemical experiments provided evidence of the cardiac DHPR isoform at the protein level in muscle fibres. The presence of the cardiac DHPR in the soleus and diaphragm is consistent with a degree of reported cardiac-like excitation-contraction coupling in these muscles, and may be an explanation for some of the therapeutic effects of theophylline in asthmatics, but is likely to serve some other role(s) as well. Received: 18 December 1997 / Received after revision: 5 March 1998 / Accepted: 17 March 1998     

Effect of monensin on the enzymes of oxidative stress, thiamine pyrophosphatase and DNA integrity in rat testicular cells in vitro.

Monensin, a sodium specific ionophore was evaluated for its in vitro effects on rat testis by studying changes at biochemical parameters as well as at the DNA level. It was observed that monensin produced marked alterations in the activities of various enzymes associated with the testicular functions. The significant inhibition of different enzymes of oxidative defense system points toward the generation of reactive oxygen species (ROS) by monensin treatment. The significant depletion of reduced glutathione and elevation in the level of lipid peroxidation further support the above findings. The significant inhibition of the activities of lactate dehydrogenase and adenosine triphosphatase shows the interference of monensin with the normal energy supply in spermatogenesis. Moreover, the significant increase in the activities of acid phosphatase and thiamine pyrophosphatase demonstrates the interference of monensin with the Golgi-lysosomal complex of the rat testis. Induced DNA fragmentation indicates towards the impact of monensin on the DNA integrity and apoptosis. Further studies are needed to understand the important molecular mechanisms responsible for these effects.     

Myositis in mice inoculated with Borrelia burgdorferi.

The authors describe the appearance of myositis in immunocompetent and immunodeficient mice after subcutaneous inoculation with Borrelia burgdorferi by histology and immunohistology. Experimental infection of mice 1) causes inflammation of striated but not smooth muscles, 2) affects the entire musculoskeletal system, and 3) is characterized by perivascular and interfacicular infiltration of mononuclear leukocytes in the striated muscle leading to necrosis as well as disruption of muscle fibers. The lesions found in striated muscle specimens were most pronounced in immunodeficient (SCID), less severe in T-cell-deficient nu/nu (BALB/c, C57BL/6) and marginal to moderate or almost not present in immunocompetent AKR/N and C.B-17 mice, respectively.     

高脂膳食和跑台运动构建模型大鼠腓肠肌葡萄糖转运体4和cAMP反应元件结合蛋白的变化

BACKGROUND: Some studies indicate that PI3K/Akt signaling pathway is associated with the expression of glucose transporter 4 (GLUT4) and the function of cAMP response element binding protein (CREB) in skeletal muscle. However, it is still unclear whether PI3K/Akt signaling pathway has the effects on CREB and GLUT4 in skeletal muscle of the rats with high-fat diet and treadmill exercise. OBJECTIVE: To investigate whether PI3K/Akt signaling pathway has the effects on CREB and GLUT4 in gastrocnemius muscle of the rats with high-fat diet and treadmill exercise.  METHODS: A total of 70 rats were fed with normal diet for 2 weeks, and randomly divided into common feed group (n=20) and high-fat feed group (n=50). Rats in both groups were respectively fed with common feed and high-fat feed for 8 weeks. The rats in the common feed group were equally assigned to common feed quiet group and common feed exercise group. 20 rats from the high-fat feed group whose body weight was 1.4 times of common rats were randomly and equally assigned to obese quiet group and obese exercise group. Rats in the quiet groups did not do exercises. Rats in the exercise groups received adaptive sports for 1 week and medium-intensity treadmill exercise for 8 weeks.  RESULTS AND CONCLUSION: (1) Impairments of PI3K/Akt signaling pathway appeared in obese rats, however, the quantity of GLUT4 expression did not change obviously in gastrocnemius muscles of obese rats. The reasons for the decrease of the nuclear protein CREB level of gastrocnemius muscles of obese rats might be related to the decrease of pAkt-Ser473 level. (2) The increase of the quantity of GLUT4 expression was accompanied by significantly up-regulated pAkt-Ser473 level by exercise intervention in gastrocnemius muscles of obese rats. Exercise intervention significantly increased the expression of nuclear protein CREB in gastrocnemius muscles of chow-fed rats and obese rats, which was consistent with the changes of pAkt-Ser473. These findings suggest that pAkt-Ser473 can play an important role in the effects of high-fat diet and exercise intervention on GLUT4 and CREB protein expression in gastrocnemius muscles of obese rats.