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@#AIM:To investigate the effect of growth hormone releasing peptide(ghrelin)on diabetic retinopathy in rats and study its protective effect.<p>METHODS: Eighteen male SD rats were divided into control group, model group and ghrelin group. HE staining was used to observe the morphology of retina, TUNEL staining was used to observe apoptosis, transmission electron microscope was used to observe the ultrastructure of retinal pigment epithelium, immunohistochemistry was used to detect oxidative stress index, and ELISA was used to detect the content of inflammatory factors. <p>RESULTS:Morphological observation showed that ghrelin could reduce the degree of retinal tissue damage and the apoptosis of retinal tissue in diabetic rats. The results of immunohistochemistry showed that the activities of SOD(superoxide dismutase)and glutathione peroxidase(GSH-Px)in retina tissue of ghrelin group were increased, and the content of malondialdehyde(MDA)was decreased, compared with model group(<i>P</i><0.05). ELISA results showed that intercellular cell adhesion molecule-1(ICAM-1), tumor necrosis factor-a,(TNF-a)and interleukin-1β(IL-1β)in model group were significantly higher than those in control group(<i>P</i><0.05). After ghrelin intervention, the expression of inflammatory factors decreased, compared with model group(<i>P</i><0.05).<p>CONCLUSION:Ghrelin could effectively retard the progression of diabetic retinopathy in diabetic rats, and its mechanism was related to lowering the level of oxidative stress and inhibiting inflammation.
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BACKGROUND: Growth hormone-releasing peptide (Ghrelin) can promote the secretion of growth hormones, regulate the balance of energy metabolism and have some unknown pharmacological properties, which are closely related to the body’s metabolic state. OBJECTIVE: To review the regulatory effect of Ghrelin on skeletal cell function and its integration in bone metabolism and energy metabolism, in order to clarify the important role of Ghrelin in skeletal development. METHODS: PubMed database was searched for relevant literature published from January 1993 to January 2017. Search words were “ghrelin, bone metabolism, leptin, osteoblast, osteoclast, castric resection, cartilage cells.” After removal of repetitive studies and inconsistent literature, 74 eligible articles were included in final analysis. RESULTS AND CONCLUSION: The remodeling of the body’s skeletal system is a highly energy-consuming process. Correspondingly, the growth and development of the skeleton involves the energy metabolism of peripheral and central nervous systems, including the sympathetic nervous system and hormones such as leptin. Recent studies abroad have shown that Ghrelin can regulate the differentiation and function of osteoblasts, induce the proliferation and differentiation of bone marrow stem cells, and regulate the state of Ghrelin-insulin axis in different ways. Ghrelin can also regulate bone metabolism and energy metabolism through interaction with leptin, thus affecting the skeletal growth.
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PURPOSE: Growth hormone secretagogues (GHSs) possess the ability to release growth hormone (GH) in the body. This study aimed to investigate the effects of MK-677, an orally active GHS, on somatic growth in rats. MATERIALS AND METHODS: The serum levels of GH were measured after oral administration of MK-677 to confirm GH stimulatory effects. Body weight, body length, tibia length, epiphyseal plate width, and serum levels of insulin-like growth factor (IGF)-I were measured after oral administration of 4 mg/kg of MK-677 for 6 weeks to investigate growth-promoting effects. RESULTS: Oral administration of MK-677 at 4 mg/kg increased peak GH concentrations by 1.8-fold, compared to baseline. However, oral administration of MK-677 for 6 weeks did not increase body growth or serum levels of IGF-I. At 6 weeks after treatment, the GH response to MK-677 was abolished. Pituitary GH mRNA and hypothalamic GH-releasing hormone mRNA, and GH secretagogue receptor (GHSR) mRNA expression in the pituitary and hypothalamus did not differ between the control and treatment group. Somatostatin (SST) mRNA expression in the hypothalamus was markedly increased in the treatment group, whereas SST receptor (SSTR)-2 mRNA expression in the pituitary gland was decreased. Protein expression of hypothalamic GHSR, SST, and pituitary SSTR-2 showed patterns similar to those for mRNA expression. CONCLUSION: Our results suggest that prolonged administration of MK-677 in rats does not promote growth despite the GH stimulatory effect of MK-677, which may be related to increased expression of SST in the hypothalamus. Further studies are needed to overcome the observed desensitization to GHS.
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Animais , Ratos , Administração Oral , Peso Corporal , Hormônio do Crescimento , Lâmina de Crescimento , Hipotálamo , Fator de Crescimento Insulin-Like I , Hipófise , RNA Mensageiro , Somatostatina , TíbiaRESUMO
To explore the effect of growth hormone releasing peptide (GHRP) on myocardial cell apoptosis in heart failure (HF) rats. Methods: Rat's HF model was established by the ligation of left anterior descending coronary artery induced ischemia. 40 male SD rats were randomly assigned into 4 groups: Normal control group, Sham operation group, HF group and GHRP treated HF group. n=10 in each group and the rats were fed for 4 weeks after the operation. Cardiac function was examined and myocardial cell morphology was observed; protein expressions of Smac/DIABL0 and Bcl-2 were measured by Western blot analysis; cell apoptosis was evaluated by FCM technique. The differences for above parameters were compared among groups to explore the effect of GHRP on myocardial cell apoptosis in HF rats. Results: Compared with HF group, GHRP treated HF group showed the less heart dilation, higher LVEF, lighter pathological changes in myocardial cells and decreased protein expression of Smac/DIABL0, all P<0.05. Bcl-2 level was lower in HF group than the other 3 groups, P<0.05. Compare with Normal control group, GHRP treated HF group had elevated Bcl-2 level, all P<0.05. Myocardial cell apoptosis index was different between HF group and GHRP treated HF group, P<0.05. Conclusion: The effect of GHRP on anti-HF should be via inhibiting myocardial cell apoptosis; the mechanism may partly be through promoting Bcl-2 protein expression and depressing Smac/DIABLO mediated mitochondrial pathway of apoptosis.
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Objective: To investigate and compare the influences of Ghrelin and growth hormone releasing peptide 6 (GHRP-6) on the contractility of stomach smooth muscle in guinea pigs, and to study the related mechanism. Methods: The myenteric plexuses of gastric fundus and antrium in guinea pigs were stimulated with electrical field stimulation (EFS) to observe the influence of Ghrelin and GHRP-6 on the contractility of stomach smooth muscle. The influences of N-nitro-L-arginine (L-NNA) and L-Arginine (L-AA) on the effect of Ghrelin and GHRP-6 were studied to disclose the mechanism of the effects of Ghrelin and GHRP-6. Results: The circular muscle tissues of the gastric fundus generated on-relaxations and off-contractions when stimulating myenteric plexuses with 1-16 Hz electrical field; the on-responses induced relaxation could be reduced by L-NNA and the off-contractions induced contraction could be blocked by atropine and guanethidine. In fundic strips, ghrelin and GHRP-6 could decrease the on-response induced relaxation and increase off-response induced contraction of the muscle, with the effect of Ghrelin obviously stronger than that of GHRP-6. L-NNA could increase the effects of Ghrelin and GHRP-6-induced muscle contraction, and L-AA could decrease their effects. In the antral strips, electrical field stimulation of myenteric plexuses led to disappearance of relaxation wave, only leaving off-contractions. Both ghrelin and GHRP-6 could increase that contraction. Conclusion: Both ghrelin and GHRP-6 can promote the contractility of stomach smooth muscle in guinea pigs through stimulating myenteric plexuses of gastric fundus and antrium, which might be related to the NO pathway.
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Objective To explore the double-labeling method of monitoring the GHRP regulatory function on [Ca2+]i and NO in cardiomyocytes of rats on real time under LSCM.Methods The reformed constant-flow Langendorff system and enzyme-dissociated was used to isolate cardiomyocytes.[Ca2+]i and NO in the cardiomyocytes of SD rats were double-labeled by their molecular probe Rhod-2/AM and DAF-FM/DA,respectively to monitor the regulatory function of GHRP on [Ca2+]i and NO on real time by LSCM.Results Ca2+ signal showed a red fluorescence and NO showed a green fluorescence while the overlapping of the two signals showed a yellow-green fluorescence by this system,and the similar effect presents in both double-labeled state and the single labeled one:GHRP induced a transient[Ca2+]i increase then followed by a plateau phase while there was not significant change in NO signal system after GHRP stimulation under the LSCM in the cardiomyocytes of rats.Conclusions After having established the double-labeling method we monitored the GHRP regulatory function on [Ca2+]i and NO on real time in cardiomyocytes of rats under LSCM causing the [Ca2+]i biphasic increase while no significant change in NO signal system.
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This article reviews a recently d is covered new peptide-growth hormone-releasing peptide: ghrelin. Ghrelin is secr eted by various tissues of body, mainly by gastric tissue. Ghrelin regulates GH release from pituitary, participates in the regulation of energy metabolism, inh ibits the proliferation of tumor cells and influences the cardiovascular functio n and the release of other hormones. The study of ghrelin in many fields is prel iminary and needs further investigation.
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PURPOSE: GH-releasing peptide(GHRP-6) was shown to possess strong GH-releasing activity both in vitro and in vivo. Chemically,GHRP-6 has no primary sequence homology with GHRH. The GH releasing activity of GHRP-6 has been demonstrated in several animal species including humans. GHRPs could have a considerable physiological and clinical useful for treatment of GH deficient and/or non GH deficient short children in the near future. The aim of this study was to evaluate the GH-releasing activity of GHRP-6 in anterior pituitary cell culture and compared to that of GHRH . METHODS: Spraque-Dawley rats were decapitated and pituitary glands were collected in ice-cold PBS. The anterior pituitaries were minced into small fragments and dissociated by enzymatic digestion. These pituitary cells were suspended in Dulbecco' modified Eagle' medium(DMEM) with fetal calf serum at a concentration of 106cells/mL and then plated onto multiwelled dishes at a density of 1.5*05 cells per 6 well plate. GHRP-6 treated group(10-8, 10-7, 10-6 M), GHRH treated group(10-8, 10-7, 10-6 M) and combined GHRP-6 and GHRH treated group were classified. After replacement of each GHRP and/or GHRH+GHRP, the released GH were measured with RIA in 10 min, 20 min, and 30 min. RESULTS: 1) GHRH(10-8) treatment increased GH release by 15.8+/-3.9ng/mL in 0 min., 69.8+/-4.3ng/mL in 10 min. 78.3+/-5.0ng/mL in 20 min. and 67.8+/-7.2ng/mL in 30 min. In case of GHRP-6(10-8M) treatment increased GH release by 11.0+/-1.4 in 0 min., 90.3+/-12.2 in 10 min., 78.3+/-4.5ng/mL in 20 min. and 78.0+/-4.8ng/mL in 30 min. The released GH levels were markedly increased in 10 min. after GHRP-6 and were not singificantly different from that of GHRH. 2)GHRP+GHRH(10-7M+10-8M) treatment increase GH release by 8.8+/-1.5ng/mL in 0 min., 37.8+/-9.3ng/mL in 10 min., 41.3+/-8.1ng/mL in 20 min. and 40.0+/-7.9ng/mL in 30 min. The released GH levels after GHRP+GHRH treatment was not markedly increased statistically compared to GHRH only. CONCLUSION: GHRP-6 could release GH in rat anterior pituitary cell culture and the released GH amounts were not significantly different from that of GHRH. There was no synergistic additive effect in GHRP+GHRH in rat pituitary cell culture.
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Animais , Criança , Humanos , Ratos , Técnicas de Cultura de Células , Digestão , Hormônio do Crescimento , Hipófise , Homologia de SequênciaRESUMO
Objective:To investigate and compare the influences of Ghrelin and growth hormone releasing peptide 6(GHRP-6) on the contractility of stomach smooth muscle in guinea pigs,and to study the related mechanism.Methods: The myenteric plexuses of gastric fundus and antrium in guinea pigs were stimulated with electrical field stimulation(EFS) to observe the influence of Ghrelin and GHRP-6 on the contractility of stomach smooth muscle.The influences of N-nitro-L-arginine(L-NNA) and L-Arginine(L-AA) on the effect of Ghrelin and GHRP-6 were studied to disclose the mechanism of the effects of Ghrelin and GHRP-6.Results: The circular muscle tissues of the gastric fundus generated on-relaxations and off-contractions when stimulating myenteric plexuses with 1-16 Hz electrical field;the on-responses induced relaxation could be reduced by L-NNA and the off-contractions induced contraction could be blocked by atropine and guanethidine.In fundic strips,ghrelin and GHRP-6 could decrease the on-response induced relaxation and increase off-response induced contraction of the muscle,with the effect of Ghrelin obviously stronger than that of GHRP-6.L-NNA could increase the effects of Ghrelin and GHRP-6-induced muscle contraction,and L-AA could decrease their effects.In the antral strips,electrical field stimulation of myenteric plexuses led to disappearance of relaxation wave,only leaving off-contractions.Both ghrelin and GHRP-6 could increase that contraction.Conclusion: Both ghrelin and GHRP-6 can promote the contractility of stomach smooth muscle in guinea pigs through stimulating myenteric plexuses of gastric fundus and antrium,which might be related to the NO pathway.