2.Expression and role of 5-HT7 receptor in brain and intestine in rats with irritable bowel syndrome.
Bai-cang ZOU ; Lei DONG ; Yan WANG ; Sheng-hao WANG ; Ming-bo CAO
Chinese Medical Journal 2007;120(23):2069-2074
BACKGROUNDThe 5-hydroxytryptamine7 receptor (5-HT(7) receptor, 5-HT(7)R) plays an important role in the regulation of smooth muscle relaxation and visceral sensation and might be involved in the pathogenesis of the gastrointestinal dyskinesia, abdominal pain and visceral paresthesia in irritable bowel syndrome (IBS). The aim of this study was to investigate the role of the 5-HT(7) receptor in the pathogenesis of IBS.
METHODSA rat model of irritable bowel syndrome with diarrhea (IBS-D) was established by colonic instillation of acetic acid and restraint stress. A rat model with irritable bowel syndrome with constipation (IBS-C) was established by stomach irrigated with 0 - 4 degrees C cool water daily for 14 days. The content and distribution of 5-HT in the brain and gut were examined by immunohistochemistry and the mRNA expression of the 5-HT(7) receptor was determined by fluorescent quantitative reverse transcription polymerase chain reaction. The accumulation of cyclic adenosine monophosphate (cAMP) in all the same tissues was measured by radioimmunity.
RESULTSThe models of IBS were reliable by identification. The immunohistochemistry results showed that there were significantly more 5-HT positive cells in the IBS-D group than in the control group in the hippocampus, hypothalamus, jejunum, ileum, proximate colon and distal colon (P < 0.05), as well as more than were found in the IBS-C group in jejunum and ileum (P < 0.05). There were more 5-HT positive cells in the IBS-C group than in the control hippocampus, hypothalamus, ileum, proximate colon, and distal colon (P < 0.05). Real time-PCR results showed that the expression level of the 5-HT(7) receptor in both the IBS-C and IBS-D groups were enhanced compared with the control group in the hippocampus and hypothalamus (P < 0.05). The expression level of 5-HT(7) receptors in the IBS-C group was notably greater when compared with the controls in the ileum and colon (P < 0.05). The cAMP accumulation in the hippocampus and hypothalamus in both the IBS-C and IBS-D groups was higher than that in the control group (P < 0.01 and P < 0.05). The cAMP accumulation in the IBS-C group was higher than that in the control group in the proximal and distal colon (P < 0.05).
CONCLUSIONSThe increased 5-HT content in the brain and intestine is related to the IBS pathogenesis. The up-regulated expression of the 5-HT(7) receptor in the brain and colon might play an important role in the pathogenesis of IBS-C.
Animals ; Brain ; metabolism ; Cyclic AMP ; metabolism ; Disease Models, Animal ; Immunohistochemistry ; Intestines ; metabolism ; Irritable Bowel Syndrome ; etiology ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Serotonin ; analysis ; genetics ; physiology ; Serotonin ; analysis
3.Effect of electro-acupuncture at different acupoints on neuropeptide and somatostatin in rat brain with irritable bowel syndrome.
Wen-Lian ZHU ; Ying LI ; Hui-Fang WEI ; Xiao-Xuan REN ; Jie SUN ; Lu-Fen ZHANG ; Jiang ZHU
Chinese journal of integrative medicine 2012;18(4):288-292
OBJECTIVETo compare the regulatory effects of electro-acupuncture (EA) at acupoints Zusanli (ST36) and Hegu (LI4) on the visceral hyper-sensitivity in the rat model of irritable bowel syndrome (IBS), and to explore the acting targets and specialty of acupoints.
METHODSExcept 8 rats of the normal control group, the rest 32 rats were prepared to set up the IBS models. IBS animal model was prepared by enema with acetic acid. Model rats were divided into three groups. Except for rats in the model group for control, those in the other two groups were treated 20 min by EA on ST36 (EA-ST36) and LI4 (EA-LI4) respectively for 2 weeks to observe the effect on behavior response of viscera sensitivity. The changes of neuropeptide (NPY), the somatostatin (SS) levels in blood and tissues of brain and intestine were monitored as well.
RESULTSThe volume thresholds for abdomen uplifting and back hunching were obviously increased after EA-ST36 (P<0.05), but showed insignificant change after EA-LI4. NPY contents lowered and SS contents increased in model rats; both EA-ST36 and EA-LI4 could raise the level of thalamic NPY (P<0.01 and P<0.05, respectively), but showed insignificant effects on NPY in colonic tissue. As for SS content, its colonic level could be reduced by EA-S36 and EA-LI4 (P<0.01 and P<0.05, respectively), however, its blood level was affected only by EA-ST36 (P<0.05).
CONCLUSIONSEA-ST36 or EA-LI4 could regulate the NPY in thalamus and SS in colonic tissue, the former could affect blood level of SS as well. It is deemed that NPY and SS may be the key substances for regulating the action of acupuncture in the brain-intestinal axis; their different levels could be regarded as an indicator for the functional difference between the acupoints.
Acupuncture Points ; Animals ; Brain ; metabolism ; Electroacupuncture ; methods ; Irritable Bowel Syndrome ; metabolism ; physiopathology ; Neuropeptide Y ; metabolism ; Rats ; Rats, Wistar ; Somatostatin ; metabolism ; Viscera ; physiopathology
4.Expression of aquaporin 8 in colonic epithelium with diarrhoea-predominant irritable bowel syndrome.
Chinese Medical Journal 2007;120(4):313-316
BACKGROUNDWe analysed and compared the aquaporin 8 (AQP8) expression in ascending and descending colon mucosa between patients with diarrhoea-predominant irritable bowel syndrome (D-IBS) and healthy volunteers, in order to study the relationship between the clinical feature of IBS, the expression of AQP8 and the pathological mechanism of D-IBS.
METHODSSpecimens were taken from the proximal ascending colon or distal descending colon of D-IBS patients (n = 26) and healthy volunteers (n = 30), and AQP8 mRNA expression of each specimen was determined by fluorescent quantitative reverse transcription polymerase chain reaction (FQ-RT-PCR). In patients with D-IBS, the relationship was analysed between AQP8 expression in both ascending and descending colons and clinical features including gender, age of onset, duration of illness, frequency of defecation, and stool characteristics.
RESULTSAlthough AQP8 was present in the epithelium of the ascending and descending colons in healthy persons and D-IBS patients, the AQP8 level of the D-IBS patients was significantly lower than that of the healthy persons (P < 0.01 in the ascending colon, P < 0.05 in the descending colon). AQP8 expression was not correlated with the age of patients with D-IBS (P > 0.05 both in the ascending and descending colons) or the age at the onset (P > 0.05 both in the ascending and descending colons), but closely with the duration of illness (P < 0.05 in the ascending colon, P < 0.01 in the descending colon), frequency of defecation (P < 0.01 in the ascending colon, P < 0.05 in the descending colon) and stool characteristics (P < 0.01 in the ascending colon, P > 0.05 in the descending colon).
CONCLUSIONSThe decreased AQP8 expression in D-IBS patients indicates that dysfunction of colonic absorption may cause reduced water absorption, loose stool and diarrhoea. The expression of AQP8 may be related to D-IBS.
Adult ; Aged ; Aquaporins ; genetics ; Colon ; metabolism ; Diarrhea ; metabolism ; Female ; Humans ; Intestinal Mucosa ; metabolism ; Irritable Bowel Syndrome ; metabolism ; Male ; Middle Aged ; RNA, Messenger ; analysis
5.Current Issues on Irritable Bowel Syndrome: Diet and Irritable Bowel Syndrome.
Jeong Hwan KIM ; In Kyung SUNG
The Korean Journal of Gastroenterology 2014;64(3):142-147
Irritable bowel syndrome (IBS) is one of the most prevalent functional gastrointestinal disorders. It is a multifactorial disorder with its pathogenesis attributed to abnormal gastrointestinal motility, low-grade inflammation, visceral hypersensitivity, communication in the gut-brain axis, and so on. Traditionally, IBS has been treated with diet and lifestyle modification, fiber supplementation, psychological therapy, and pharmacological treatment. Carbohydrates are intermingled with a wide range of regularly consumed food including grains such as rye and wheat, vegetables, fruits, and legumes. Short-chain carbohydrates that are poorly absorbed exert osmotic effects in the intestinal lumen increasing its water volume, and are rapidly fermented by bacteria with consequent gas production. These effects may be the basis for the induction of most of the gastrointestinal symptoms. This has led to the use of lactose-free diets in those with lactose intolerance and of fructose-reduced diets for fructose malabsorption. As all poorly absorbed short-chain carbohydrates have similar and additive effects in the intestine, a concept has been developed to regard them collectively as FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) and to evaluate a dietary approach that restricts them all. Based on the observational and comparative studies, and randomized-controlled trials, FODMAPs have been shown to trigger gastrointestinal symptoms in patients with IBS. Food choice via the low FODMAPs and potentially other dietary strategies is now a realistic and efficacious therapeutic approach for managing symptoms of IBS.
*Diet, Carbohydrate-Restricted
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Dietary Supplements
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Humans
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Hypersensitivity/complications
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Inflammation/complications
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Intestines/pathology
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Irritable Bowel Syndrome/complications/*diagnosis/diet therapy
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Malabsorption Syndromes/complications
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Monosaccharides/metabolism
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Oligosaccharides/metabolism
6.Small intestine motility and gastrointestinal hormone levels in irritable bowel syndrome.
Ju-Hui ZHAO ; Lei DONG ; Xiao-Qian HAO
Journal of Southern Medical University 2007;27(10):1492-1495
OBJECTIVETo investigate the relationship between interdigestive migrating motor complex (MMC) and plasma gastrointestinal hormones in patients with diarrhea or constipation-predominant irritable bowel syndrome (IBS) to elucidate the pathophysiology of IBS.
METHODSA small intestine manometry was used to record the MMC cycles for at least 4-6 h in 19 IBS patients and 10 healthy volunteers. The plasma gastrointestinal hormone levels were examined according to altered MMC phases.
RESULTSCompared with the healthy controls, IBS-D patients exhibited shortened duration of the small intestinal MMC cycle, prolonged phase III duration with greater amplitude, as well as faster propagation velocity, whereas the contrary alterations were found in IBS-C patients. The peak plasma motilin level occurred in phase III of the MMC cycle. The plasma somatostatin level was higher in IBS groups than in the healthy controls, but comparable between the diarrhea and constipation groups. Plasma 5-hydroxytryptamine showed periodical fluctuations with the phases of MMC cycles, reaching the peak level in phase II. IBS-D patients had higher 5-hydroxytryptamine levels than IBS-C patients and the healthy controls.
CONCLUSIONSPlasma hormone levels are correlated with the MMC cycles, and the hormone level changes and small intestine motility disorder may play important roles in IBS pathophysiology.
Adult ; Case-Control Studies ; Female ; Gastrointestinal Hormones ; metabolism ; Gastrointestinal Motility ; Humans ; Intestine, Small ; physiopathology ; Irritable Bowel Syndrome ; metabolism ; physiopathology ; Male ; Middle Aged ; Young Adult
7.Effect of Shen warming Pi strengthening method on the expression of serum T cell subsets in IBS-D rats.
Xiao-lan SU ; Ru-han WEI ; Wei WEI ; Jing ZHANG ; Yi-bing BAI ; Hai-xia SHI
Chinese Journal of Integrated Traditional and Western Medicine 2015;35(4):457-460
OBJECTIVETo observe the effect of Shen warming Pi strengthening method on expressions of serum T cell subsets (C045+%, C03+%, and C04 +/COB+) in diarrhea-predominant irritable bowel syndrome (IBS-0) rats. Methods An IBS-0 rat model was established referring to AL-Chaer's modeling method combined with tail clamp and intragastric administration of sanna leaf. After modeling 30 SO rats were randomly divided into 6 groups according to random digit table, i.e., the model group, the high, middle, low dose Wenshen Jianpi Recipe (WJR) groups, and the Sishen Pill control group, 6 in each group. A normal control group consisting of 6 SO rats were also set up. Rats in high, middle, low dose WJ R groups were administered by gastrogavage with boil-free WJ R at the daily dose of 3. 100, 1. 550, 0. 775 g/kg, respectively. Rats in the Sis hen Pill control group were administered by gastrogavage with boil-free Sis hen Pill at the daily dose of 0. 736 g/kg. Equal volume of normal saline was given by gastrogavage to rats in the model group and the normal control group. All medication lasted for 2 successive weeks. Rats' general state, expressions of T cell subsets (CD45+%, CD3+%, and CD4+ /CDB+) changes were observed.
RESULTSCompared with the normal control group, expressions of CD45+% and CD3+% increased, but CD4+ /CDB+ decreased with statistical difference (P < 0. 05). Compared with the model group, expressions of CD45+% and CD3+% decreased, but CD4+ ICDB+ increased with statistical difference in high, middle, low dose WJR groups, and the Sis hen Pill control group (P <0. 05). Compared with the Sis hen Pill control group, there was statistical difference in all indices except CD45+ value in the low dose SWPSM group (P <0. 05). Compared with the low dose WJ R group, the expression of CD3+% decreased in high and middle dose WJR groups, and the Sis hen Pill control group; CD4+ /CD8+ increased in the Sishen Pill control group and the high dose SWPSM group (all P < 0. 05).
CONCLUSIONSWJR showed better treatment effect. The mechanism of Shen warming Pi strengthening method might be achieved by regulating expressions of CD45+% and CD3+%, and CD4+ /CD8+ ratios.
Animals ; Drugs, Chinese Herbal ; Female ; Irritable Bowel Syndrome ; therapy ; Leukocyte Common Antigens ; metabolism ; Medicine, Chinese Traditional ; Rats ; T-Lymphocyte Subsets ; metabolism
8.The Role of Protease Activated Receptors and Proteases in Subtly Inflamed Diarrhea-Predominant Irritable Bowel Syndrome.
The Korean Journal of Gastroenterology 2014;63(1):59-61
No abstract available.
Animals
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Colon/*metabolism
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Constipation/*physiopathology
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Diarrhea/*physiopathology
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Female
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Ganglia, Spinal/*cytology
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Humans
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Irritable Bowel Syndrome/*physiopathology
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Male
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Nociceptors/*physiology
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Receptor, PAR-2/*physiology
9.Linderae Radix water extract treats diarrhea-predominant irritable bowel syndrome in rats: a serum metabolomics study.
Tao LIU ; Meng-Ling WU ; Guo-Yan DENG ; Yang HE ; Yi-Ran HE ; Gui-Ming DENG ; Lin-Qi OUYANG
China Journal of Chinese Materia Medica 2023;48(19):5356-5364
This study aims to investigate the mechanism of Linderae Radix water extract(LRWE) in the prevention and treatment of diarrhea-predominant irritable bowel syndrome(IBS-D) based on serum metabolomics. Eighteen 2-week-old male SD rats were randomized into control, IBS-D model, and LRWE groups. The rats in other groups except the control group received gavage of senna concentrate combined with restraint stress for the modeling of IBS-D. The rats in the LRWE group were administrated with LRWE(5.4 g·kg~(-1)) by gavage, and those in the control and IBS-D model groups with an equal volume of distilled water for a total of 14 days. The visceral sensitivity was evaluated by the abdominal withdrawal reflex(AWR) score, and the degree of diarrhea was assessed by the fecal water content(FWC). The morphological changes of the colon and the morphology and number of goblet cells were observed by hematoxylin-eosin(HE) and periodic acid-schiff(PAS) staining, respectively. Ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) was used for the screening of the potential biomarkers in the rat serum and their related metabolic pathways. The results showed that LRWE reduced the AWR score, decreased FWC, and alleviated visceral sensitivity and diarrhea symptoms in IBS-D rats. HE and PAS staining showed that LRWE mitigated low-grade intestinal inflammation and increased the number of mature secretory goblet cells in the colonic epithelium of IBS-D rats. A total of 25 potential biomarkers of LRWE in treating IBS-D were screened out in this study, which were mainly involved in riboflavin, tryptophan, glycine, serine and threonine metabolism, glyoxylate and dicarboxylate metabolism, and cysteine and methionine metabolism. The regulatory effects were the most significant on the riboflavin and tryptophan metabolism pathways. LRWE may alleviate the visceral hypersensitivity by promoting energy metabolism and amino acid metabolism, enhancing intestinal barrier function, and improving intestinal immune function in IBS-D rats.
Rats
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Male
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Animals
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Irritable Bowel Syndrome/metabolism*
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Water
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Chromatography, Liquid
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Tryptophan
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Rats, Sprague-Dawley
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Tandem Mass Spectrometry
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Diarrhea/drug therapy*
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Biomarkers
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Riboflavin
10.Effects of acupoint area and non-acupoint area of eye-acupuncture on expressions of VIP and AQP 8 in colonic tissues in rats with D-IBS.
Hui-Hui LIU ; Xu-Dong LIU ; Yan-Jie WANG ; Hong-Quan GUAN ; Ji-Yan CHAI ; Jin-Ru ZHAO ; De-Shan WANG
Chinese Acupuncture & Moxibustion 2012;32(10):919-924
OBJECTIVETo explore the point specificity of eye-acupuncture and the mechanism of eye-acupuncture on diarrhea-predominant irritable bowel syndrome (D-IBS).
METHODSForty male Wistar rats of SPF grade were randomly divided into a normal group, a model group, a eye-acupuncture point (AA) group and a non-point (NA) group. The D-IBS rat model was established with the combination methods of the chronic stress and binding limbs. The AA group was treated by acupuncture at "low energizer area", "large intestine area", "liver area" and "spleen area", and the NA group by acupuncture at 3 mm apart from the same points area mentioned above, and the normal group and the model group with no intervention. The rate of feces moisture content was detected. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA of aquaporin 8 (AQP 8) in colon. Protein expressions of the vasoactive intestinal peptide (VIP) and AQP 8 in colon were detected by SABC immunohistochemistry method.
RESULTSCompared with normal group, the rate of feces moisture content at the 18th and 25th days, VIP protein in colon mucosa, myenteric nerve plexus and hypo-mucosa nerve plexus increased significantly (all P < 0.01), and AQP 8 mRNA in colon mucosa decreased significantly in model, AA and NA group (P < 0.05, P < 0.01); AQP 8 protein in colon mucosa decreased significantly in model group and NA group (both P < 0.01). Compared with model group, the rate of feces moisture content at the 25th day and VIP protein in colon mucosa decreased significantly (P < 0.01, P < 0.05), and AQP 8 mRNA and protein increased significantly (P < 0.05, P < 0.01) in AA group. Compared with AA group, the rate of feces moisture content at the 25th day and VIP protein in colon mucosa increased significantly (both P < 0.01), and AQP 8 mRNA and protein decreased significantly (both P < 0.01) in NA group.
CONCLUSIONEye-acupuncture has a good therapeutic effect on D-IBS. It is suggested that one of the mechanism is relate to increase AQP 8 in colon tissue and restrain the expression of VIP. Non-point area of eye-acupuncture has no obviously therapeutic effect and so to illustrate the point specificity of eye-acupuncture.
Acupuncture Points ; Acupuncture Therapy ; Animals ; Aquaporins ; genetics ; metabolism ; Colon ; metabolism ; Diarrhea ; genetics ; metabolism ; therapy ; Humans ; Irritable Bowel Syndrome ; genetics ; metabolism ; therapy ; Male ; Rats ; Rats, Wistar ; Vasoactive Intestinal Peptide ; genetics ; metabolism