1.Expression of ghrelin and insulin-like growth factor-1 in immature piglet model of chronic cyanotic congenital heart defects with decreased pulmonary blood flow.
Dong WANG ; Ying-long LIU ; Xiao-dong LÜ ; Yao-bin ZHU ; Feng LING ; Ai-jun LIU ; Gang LI ; Yu-lin XU
Chinese Medical Journal 2011;124(15):2354-2360
BACKGROUNDCyanotic patients have potential growth retardation and malnutrition due to hypoxemia and other reasons. Ghrelin is a novel endogenous growth hormone secretagogue that has effects on growth and cardiovascular activities. The aim of this study was to evaluate the plasma level and myocardial expression of ghrelin and insulin-like growth factor-1 (IGF-1) using an immature piglet model of chronic cyanotic congenital heart defects with decreased pulmonary blood flow.
METHODSTwelve weanling Chinese piglets underwent procedures of main pulmonary artery-left atrium shunt with pulmonary artery banding or sham operation as control. Four weeks later, hemodynamic parameters were measured. Enzyme-linked immunosorbent assay for plasma ghrelin and IGF-1 level measurement were performed. Ventricular ghrelin and IGF-1 mRNA expressions were measured by quantitative real-time polymerase chain reaction.
RESULTSFour weeks after surgical procedure, the cyanotic model produced lower arterial oxygen tension ((68.73 ± 15.09) mmHg), arterial oxygen saturation ((82.35 ± 8.63)%), and higher arterial carbon dioxide tension ((51.83 ± 6.12) mmHg), hematocrit ((42.67 ± 3.83)%) and hemoglobin concentration ((138.17 ± 16.73) g/L) than the control piglets ((194.08 ± 98.79) mmHg, (96.43 ± 7.91)%, (36.9 ± 4.73) mmHg, (31.17 ± 3.71)%, (109.83 ± 13.75) g/L) (all P < 0.05). Plasma ghrelin level was significantly higher in the cyanotic model group in comparison to the control (P = 0.004), and the plasma IGF-1 level was significantly lower than control (P = 0.030). Compared with control animals, the expression of ghrelin mRNAs in the ventricular myocardium was significantly decreased in the cyanotic model group (P = 0.000), and the expression of IGF-1 mRNAs was elevated (P = 0.001).
CONCLUSIONSChronic cyanotic congenital heart defects model was successfully established. Plasma ghrelin level and myocardial IGF-1 mRNA expression were significantly up-regulated, while plasma IGF-1 level and myocardial ghrelin mRNA expression were down-regulated in the chronic cyanotic immature piglets. The ghrelin system may be an important part of the network regulating cardiac performance.
Animals ; Cyanosis ; blood ; metabolism ; physiopathology ; Female ; Ghrelin ; blood ; metabolism ; Heart Defects, Congenital ; blood ; metabolism ; physiopathology ; Insulin-Like Growth Factor I ; genetics ; metabolism ; Male ; Pulmonary Circulation ; physiology ; Swine
2.Eradication of Helicobacter pylori Increases Ghrelin mRNA Expression in the Gastric Mucosa.
Eon Sook LEE ; Yeong Sook YOON ; Cheol Young PARK ; Han Seong KIM ; Tae Hyun UM ; Hyun Wook BAIK ; Eun Jeong JANG ; Sangyeoup LEE ; Hee Soon PARK ; Sang Woo OH
Journal of Korean Medical Science 2010;25(2):265-271
It has been suggested that Helicobacter pylori eradication may influence production of some peptides in the stomach, which can affect appetite. This hypothesis is controversial. To verify the hypothesis, we conducted this randomized controlled trial using H. pylori infected subjects without any gastrointestinal symptoms. The treatment group received triple H. pylori eradication therapy for 7 days and the control group received no medication. We measured ghrelin, obestatin and the tumor necrosis factor-alpha (TNF-alpha) mRNA levels in endoscopic biopsy specimens and the changes from baseline to follow-up. The plasma active n-octanoyl ghrelin and obestatin levels were measured in both groups. The ghrelin/obestatin ratios in plasma and gastric mRNA expression were calculated at baseline and follow-up. Ghrelin mRNA expression in the fundic mucosa after H. pylori eradication increased significantly compared to the control group (4.47+/-2.14 vs. 1.79+/-0.96, P=0.009), independent of inflammatory changes. However, obestatin mRNA expression decreased in the antral mucosa (-0.57+/-1.06 vs. 0.41+/-0.72, P=0.028). The treatment group showed a marginal increase (P=0.060) in plasma ghrelin/obestatin ratio. The TNF-alpha mRNA expression also decreased significantly with treatment. This randomized controlled trial demonstrates that H. pylori eradication increases ghrelin mRNA expression, independent of inflammatory cell changes.
Adult
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Aged
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Anti-Bacterial Agents/therapeutic use
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Female
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Gastric Mucosa/*metabolism/microbiology
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Gastroscopy
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Ghrelin/blood/genetics/*metabolism
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Helicobacter Infections/drug therapy/genetics/*metabolism
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*Helicobacter pylori
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Humans
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Male
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RNA, Messenger/metabolism
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Tumor Necrosis Factor-alpha/genetics/metabolism
3.Age-dependent alteration of insulin and ghrelin expression in pancreatic islets of intrauterine growth-retarded rats.
Xiu-Min WANG ; Li LIANG ; Li-Zhong DU
Journal of Zhejiang University. Medical sciences 2008;37(3):226-232
OBJECTIVETo evaluate the age-dependent alteration of insulin and ghrelin expression in the pancreatic islets of intrauterine growth-retarded (IUGR) rats during development and to identify the role of ghrelin in insulin resistance induced by IUGR.
METHODSNeonatal SD rats were divided into normal birth weight group (N group) and intrauterine growth-retarded group (I group). Plasma glucose, ghrelin and serum insulin were analyzed at day 1, 3, 7 and 10 and at week 2, 3, 4,8 and 12 after birth.Entire pancreas samples were collected for determination of ghrelin and insulin mRNA. Immunohistochemical double-staining and confocal microscopy was performed on rat pancreas.
RESULTPlasma insulin levels of I group were lower than those of N group at day 1, 3 and 7 (P <0.05). The homeostasis model assessment-insulin resistance index (HOMA-IR) of I group was higher than that of N group at day 1, 3 and 7 (P<0.05). Plasma glucose levels, insulin, HOMA-IR and ghrelin concentrations decreased in an age-dependent manner (F = 4.12 to approximately 125.97, P <0.001) in both groups. Plasma ghrelin level was correlated with HOMA-IR in I group(r=0.553, P=0.000). Pancreatic ghrelin contents, pancreatic ghrelin mRNA expression, the percentage of insulin (+) cells and ghrelin (+) cells in both groups decreased in an age-dependent manner (F = -49.29 to approximately 427.28, P<0.001). There were differences in the above indexes between N and I group (F = -69.98 to approximately 169.22, P<0.05). Insulin secretion was negatively correlated with ghrelin contents in both groups (r=-0.895, P=0.000; r=-0.458, P=0.002). Percentage of insulin(+) cells was negatively correlated with the percentage of ghrelin (+) cells in pancreatic islets in both groups (r=-0.810,P=0.000; r=-0.714, P=0.000). The distributions of ghrelin (+) cells in pancreatic islets of I group were different from those of N group.
CONCLUSIONThe effects of IUGR on weight, plasma ghrelin levels and insulin secretion of pups rats persist after birth and ghrelin may be involved in the process of insulin resistance in IUGR rats.
Animals ; Animals, Newborn ; Female ; Fetal Growth Retardation ; genetics ; metabolism ; Ghrelin ; blood ; metabolism ; Insulin ; blood ; metabolism ; Insulin Resistance ; physiology ; Insulin-Secreting Cells ; metabolism ; Pregnancy ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley
4.Protective effect of ghrelin on left ventricular remodeling in spontaneously hypertensive rats is associated with the peroxisome proliferator-activated receptor gamma-dependent pathway.
Zhao LI ; Xiao-ying ZHU ; Meng LI ; Ying-long BAI ; Jian HU
Chinese Medical Journal 2008;121(22):2299-2304
BACKGROUNDStudies suggested that exogenous ghrelin administration could prevent early left ventricular remodeling in rats with myocardial infarction. We investigated herein whether ghrelin attenuated left ventricular remodeling induced by hypertension and whether ghrelin's effect was mediated through the peroxisome proliferator-activated receptor gamma (PPAR-gamma)-dependent pathway.
METHODSSpontaneously hypertensive rats (8-week-old males) were randomly divided into three groups with 12 rats in each: ghrelin group (received ghrelin 100 microg/kg subcutaneously (s.c.) twice daily); ghrelin + GW9662 group (received the PPAR-gamma antagonist GW9662 at 2 mg/kg s.c., and then ghrelin as above); saline controls. Normal male Wistar Kyoto rats (n = 12) served as normal controls. Four weeks later, the effects of ghrelin on cardiac remodeling were evaluated by echocardiographic, hemodynamic, and histopathological examination, and gene expression analysis (PPAR-gamma protein and mRNA expression). The serum levels of C-reactive protein (CRP) and tumor necrosis factor (TNF)-alpha were detected by enzyme linked immunosorbent assay.
RESULTSGhrelin prevented ventricular remodeling, increased PPAR-gamma expression in the myocardium, suppressed collagen I and collagen III mRNA expression, and also decreased the serum levels of TNF-alpha, but not CRP. All abovementioned effects of ghrelin were inhibited by GW9662.
CONCLUSIONGhrelin inhibited ventricular remodeling induced by hypertension, and the preventive effects of ghrelin may be mediated by the anti-inflammatory actions of the PPAR-gamma-dependent pathway.
Anilides ; pharmacology ; Animals ; Blotting, Western ; C-Reactive Protein ; metabolism ; Collagen ; genetics ; metabolism ; Echocardiography ; Enzyme-Linked Immunosorbent Assay ; Ghrelin ; pharmacology ; Male ; PPAR gamma ; antagonists & inhibitors ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; drug effects ; Tumor Necrosis Factor-alpha ; blood ; Ventricular Remodeling ; drug effects