Реферат
BACKGROUND/AIMS: Abnormal visceral sensitivity and disordered motility are common in patients with diabetes mellitus. The purpose of the present study was to investigate whether visceral sensation and bowel motility were altered in a rat model of type 2 diabetes mellitus accompanied by weight loss. METHODS: A type 2 diabetic rat model in adulthood was developed by administrating streptozotocin (STZ; 90 mg/kg, i.p.) to neonatal rats. Eight weeks after STZ administration, rats with blood glucose level of 200 mg/dL or higher were selected and used as diabetic group (n = 35) in this study. Abdominal withdrawal reflex and arterial pulse rate were measured to examine visceral nociception induced by colorectal distension (0.1-1.0 mL). The amplitude, frequency, and area under the curve (AUC) of spontaneous phasic contractions of colonic circular muscles were recorded in vitro to examine colonic motility. RESULTS: STZ-treated diabetic rats gained significantly less weight for 8 weeks than control (P < 0.01). Forty-eight percent of the diabetic rats showed enhanced visceral nociceptive response to colorectal distension. Diabetic rats did not differ from control rats in colorectal compliance. However, the frequency and AUC, not the amplitude, of colonic spontaneous contraction in vitro was significantly decreased in diabetic rats compared to control rats (P < 0.01 in frequency and P < 0.05 in AUC). CONCLUSIONS: These results demonstrate visceral hypersensitivity and colonic dysmotility in a rat model of type 2 diabetes mellitus accompanied by weight loss.
Тема - темы
Animals , Humans , Rats , Area Under Curve , Blood Glucose , Colon , Compliance , Diabetes Mellitus , Diabetes Mellitus, Type 2 , Heart Rate , Hypersensitivity , Models, Animal , Muscles , Nociception , Reflex , Sensation , Streptozocin , Weight LossРеферат
Single-channel recordings of TASK-1 and TASK-3, members of two-pore domain K+ channel family, have not yet been reported in dorsal root ganglion (DRG) neurons, even though their mRNA and activity in whole-cell currents have been detected in these neurons. Here, we report single-channel kinetics of the TASK-3-like K+ channel in DRG neurons and up-regulation of TASK-3 mRNA expression in tissues isolated from animals with spinal cord injury (SCI). In DRG neurons, the single-channel conductance of TASK-3-like K+ channel was 33.0+/-0.1 pS at -60 mV, and TASK-3 activity fell by 65+/-5% when the extracellular pH was changed from 7.3 to 6.3, indicating that the DRG K+ channel is similar to cloned TASK-3 channel. TASK-3 mRNA and protein levels in brain, spinal cord, and DRG were significantly higher in injured animals than in sham-operated ones. These results indicate that TASK-3 channels are expressed and functional in DRG neurons and the expression level is up-regulated following SCI, and suggest that TASK-3 channel could act as a potential background K+ channel under SCI-induced acidic condition.
Тема - темы
Animals , Humans , Rats , Acidosis , Brain , Clone Cells , Diagnosis-Related Groups , Ganglia, Spinal , Hydrogen-Ion Concentration , Kinetics , Neurons , RNA, Messenger , Spinal Cord , Spinal Cord Injuries , Spinal Nerve Roots , Up-RegulationРеферат
Nitric oxide (NO) is a non-adrenergic, non-cholinergic neurotransmitter found in the enteric nervous system that plays a role in a variety of enteropathies, including inflammatory bowel disease. Alteration of nitrergic neurons has been reported to be dependent on the manner by which inflammation is caused. However, this observed alteration has not been reported with acetic acid-induced colitis. Therefore, the purpose of the current study was to investigate changes in nitrergic neuromuscular transmission in experimental colitis in a rat model. Distal colitis was induced by intracolonic administration of 4% acetic acid in the rat. Animals were sacrificed at 4 h and 48 h postacetic acid treatment. Myeloperoxidase activity was significantly increased in the acetic acid-treated groups. However, the response to 60 mM KCl was not significantly different in the three groups studied. The amplitude of phasic contractions was increased by Nomega-nitro-L-arginine methyl ester (L-NAME) in the normal control group, but not in the acetic acid-treated groups. Spontaneous contractions disappeared during electrical field stimulation (EFS) in normal group. However, for the colitis groups, these contractions initially disappeared, and then reappeared during EFS. Moreover, the observed disappearance was diminished by L-NAME; this suggests that these responses were NO-mediated. In addition, the number of NADPH-diaphorase positive nerve cell bodies, in the myenteric plexus, was not altered in the distal colon; whereas the area of NADPH-diaphorase positive fibers, in the circular muscle layer, was decreased in the acetic acidtreated groups. These results suggest that NO-mediated inhibitory neural input, to the circular muscle, was decreased in the acetic acid-treated groups.
Тема - темы
Animals , Male , Rats , Acetic Acid/toxicity , Colitis/chemically induced , Colon/drug effects , Indicators and Reagents/toxicity , Muscle Contraction/drug effects , Muscle, Smooth/drug effects , Myenteric Plexus/pathology , NADPH Dehydrogenase/metabolism , NG-Nitroarginine Methyl Ester/pharmacology , Neuromuscular Junction/drug effects , Nitrergic Neurons/drug effects , Nitric Oxide/metabolism , Peroxidase/metabolism , Potassium Chloride/pharmacology , Rats, Sprague-DawleyРеферат
The involvement of mucosal mast cells (MMC) in the pathophysiology of irritable bowel syndrome (IBS) is still controversial. We aimed to re-evaluate the role of MMC in visceral hypersensitivity associated with IBS using a rat IBS model that develops the IBS symptom after a subsidence of acetic acid-induced colitis. No significant difference in the number of MMC was observed between normal rat colon and IBS rat colon. (61.7 +/-2.9/mm 2 in normal vs. 88.7 +/-13.3/mm 2 in IBS, p >0.29). However, the degranulation rate of MMC was significantly higher in IBS rat colon (49.5 +/-2.4% in normal vs. 68.8 +/-3.4% in IBS, p >0.05). Pretreatment of a mast cell stabilizer, doxantrazole (5 mg/kg, i.p.), reduced the degranulation rate of MMC and significantly attenuated visceral hypersensitivity to rectal distension in IBS rat, whereas it had no effect on the visceral sensory responses in normal rat. These results suggest that, although the number of MMC is not significantly changed in IBS rat colon, the higher degranulation rate of MMC is responsible for visceral hypersensitivity in this model IBS.
Тема - темы
Animals , Male , Rats , Acetic Acid/toxicity , Cell Count , Colitis/chemically induced , Hypersensitivity/pathology , Image Processing, Computer-Assisted , Intestinal Mucosa/pathology , Irritable Bowel Syndrome/pathology , Mast Cells/drug effects , Models, Theoretical , Phosphodiesterase Inhibitors/pharmacology , Rats, Sprague-Dawley , Thioxanthenes/pharmacology , Viscera/immunology , Xanthones/pharmacologyРеферат
The effect of electroacupuncture (EA) on experimental colitis was investigated in Sprague-Dawley rats. Colitis was induced by intracolonic instillation of 4% acetic acid. EA (2 Hz, 0.05 ms, 2 V for 20min) was applied to bilateral Hoku (LI-4) and Zusanli (ST-36) on 12 hrs and 36 hrs after induction of colitis. EA-treatment significantly reduced the macroscopic damage and the myeloperoxidase activity of colonic samples at 3 days post-induction of colitis. Colitic colon showed a decreased in vitro motility. However, colonic motility of EAtreated group was not significantly different from that of normal group. The anti-inflammatory effect of EA was not inhibited by a glucocorticoid receptor antagonist, RU-486, but suppressed by a beta-adrenoceptor antagonist, propranonol. These results suggest that EA-treatment has a beneficial effect on colitis, and its anti-inflammatory effect is mediated by beta-adrenoceptor activation but not by endogenous glucocorticoiddependent mechanism.