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ObjectiveTo investigate the mechanism of Akkermansia muciniphila （A. muciniphila） regulating the visceral hypersensitivity in irritable bowel syndrome （IBS） rats induced by neonatal maternal separation （MS） and water avoidance stress （WAS）. MethodsNeonatal male Sprague-Dawley rats were randomly divided into sham WAS group （blank group）， MS+WAS group （IBS model group） and A. muciniphila group. IBS model was established by MS combined with WAS in both IBS model group and A. muciniphila group. Meanwhile， the rats in the A. muciniphila group were given 1 mL 1×109 CFU/mL A. muciniphila by gavage daily for 10 days. Visceral pain responses were detected by behavioral observations and abdominal withdrawal reflex scores. ResultsCompared with IBS model group， A. muciniphila group exhibited significant increase of body weight and visceral pain threshold， significantly decreased numbers of fecal particles and proportions of unformed stools， significantly higher expression levels of cannabinoid receptor type 2 （CB2R） mRNA in colon tissues. ConclusionA. muciniphila may alleviate the visceral hypersensitivity in IBS rats by regulating the expression of CB2R mRNA in colonic tissues.
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ObjectiveTo explore the clinical efficacy and mechanism of Tongxie Yaofang in treating diarrhea-predominant irritable bowel syndrome（IBS-D） patients with liver depression and spleen deficiency. MethodA total of 168 IBS-D patients with liver depression and spleen deficiency who were treated from August 2017 to June 2021 were divided into observation group and control group by random number table，84 in each group. The observation group was administrated with Tongxie Yaofang decoction-free granules orally，and the control group received oral treatment of pinaverium bromide，both for 4 weeks. The main symptoms of IBS were compared before and after treatment，such as the degree of abdominal pain，stool changes，traditional Chinese medicine pattern curative effect scoring system（TCM-PES），IBS quality of life questionnaire （IBS-QOL），IBS symptom severity scale（IBS-SSS），self-rating anxiety scale （SAS），and self-rating depression scale（SDS）. Nimodipine was used to evaluate the efficacy based on TCM syndrome score of liver depression and Qi stagnation. Enzyme-linked immunosorbent assay（ELISA） was conducted to detect the plasma interleukin-10（IL-10）and IL-12 before and after treatment. ResultAfter 4 weeks of treatment， the response rate of abdominal pain in observation group was 92.86% （78/84）， higher than that in control group （82.14%， 69/84）（χ2=6.254，P<0.05）. The response rates of diarrhea in observation group and control group were 91.67% （77/84）and 77.38% （65/84）， respectively（χ2=8.214，P<0.01）. TCM-PES and IBS-QOL scores of observation group after treatment were higher and IBS-SSS score was lower than those of control group （P<0.05）. The efficacy rate of TCM syndromes in observation group was higher than that of control group （P<0.05）. Additionally， after treatment， the observation group had lower SAS and SDS scores （P<0.05）and IL-12 level（P<0.05）and higher plasma IL-10 level than the control group （P<0.05）. ConclusionTongxie Yaofang can relieve abdominal pain and diarrhea in IBS-D patients with liver depression and spleen deficiency，reduce negative emotion，and improve the quality of life of patients，which may be related to alleviating the visceral hypersensitivity.
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OBJECTIVE@#To observe the effect of blistering moxibustion on the expression levels of 5-hydroxytyptamine (5-HT) and its receptors of the colon tissue in the mice with visceral hypersensitivity of irritable bowel syndrome (IBS), so as to explore the effect mechanism of blistering moxibustion in treatment of IBS.@*METHODS@#Forty SPF-grade newborn Kunming mice were randomly divided into a normal group, a model group, an antagonist group and a blistering moxibustion group, 10 mice in each one. Before modeling, the injection with 0.2 mL parachlorophenylalanine (PCPA) was given on the lateral ventricle in the antagonist group. The endorectal glacial acetic acid stimulation combined with tail clipping was used to prepare the model of visceral hypersensitivity of IBS in the model group, the antagonist group and the blistering moxibustion group. After modeling, in the blistering moxibustion group, the intervention with blistering moxibustion was exerted at "Zhongwan" (CV 12), "Tianshu" (ST 25) and "Zusanli" (ST 36), once herbal irritant plaster at each acupoint, for 2 h each time, once a week, consecutively for 3 weeks. Abdominal withdrawal reflex (AWR) score and electromyographic (EMG) amplitude of abdominal muscles were adopted to evaluate the visceral hypersensitivity. HE staining was applied to observe the morphological changes in colon tissue, and immunohistochemistry was to determine the expression levels of 5-HT and its receptors.@*RESULTS@#Compared with the normal group, EMG amplitude of abdominal muscles was increased under 20, 40 mm Hg (1 mm Hg=0.133 kPa) in the model group (P<0.05), AWR scores and EMG amplitude of abdominal muscles under 60, 80 mm Hg were all increased in the model group (P<0.05). In comparison with the model group, EMG amplitude of abdominal muscles was reduced under 20 mm Hg in the blistering moxibustion group (P<0.05), AWR scores were increased under 40 mm Hg in both the blistering moxibustion group and the antagonist group (P<0.05); AWR scores and EMG amplitude of abdominal muscles under 60, 80 mm Hg were all reduced in both the blistering moxibustion group and the antagonist group (P<0.05). Compared with the normal group, in the model group, the mucosa was slightly disturbed, while, the moderate inflammatory cells were visible in the submucosa. In comparison with the model group, the inherent glands of mucosa were regular in shape and a small number of inflammatory cells were visible in both the blistering moxibustion group and the antagonist group. In comparison with the normal group, the average positive staining area percentage (APSAP) of 5-HT and 5-HT3R of the colon tissue was increased, while, APSAP of 5-HT4R was reduced in the model group (P<0.05). Compared with the model group, APSAP of 5-HT and 5-HT3R was reduced in both the blistering moxibustion group and the antagonist group (P<0.05).@*CONCLUSION@#Blistering moxibustion can relieve the visceral hypersensitivity of the mice with visceral hypersensitive IBS and the underlying mechanism is related to the regulation of the gut-brain axis mediated by 5-HT signaling pathway.
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Animals , Mice , Rats , Disease Models, Animal , Hypersensitivity , Irritable Bowel Syndrome/therapy , Moxibustion , Rats, Sprague-Dawley , Serotonin , Signal TransductionABSTRACT
Objective:To explore the effect of Tongxie-Yaofang on visceral sensitivity in IBS-D and the possible mechanism. Methods:Divided 30 male SD rats (one-day old) into normal group (10 rats) and IBS-D model group (20 rats) randomly. IBS-D was induced by the method of neonatal maternal separation and restraint stress. After successful modeling, the IBS-D model group was randomly divided into model group and Tongxie-Yaofang group, with 10 rats in each group. Tongxie-Yaofang group was given Tongxie-Yaofang formula, 4.92 g/ml by gavage, while the normal and model groups were given the same amount of normal saline, rats were gavaged with 2 ml/100 g body weight once a day for 14 days. The electromyography of the exorectus muscle was used to meature colorectal distension and by using electronic constant pressure apparatus to evaluate visceral sensitivity. The morphology of colon by HE staining and Enzyme-linked immunosorbent assay (ELISA) were used to determine the level of colonic 5-hydroxytryptamine (5-HT), qPCR was used to detect the colonic mRNA expression of serotonin transporter (SERT) and Western blot was used to detect SERT expression in colon and hypothalamus. Results:Compared with the model group, at the expansion pressure of 60 mmHg and 80 mmHg, the electromyographic response [(179.51 ± 18.26)% vs. (226.42 ± 25.78)%; (242.13 ± 15.42)% vs. (306.02 ± 51.51)%] in Tongxie-Yaofang group was significantly decreased ( P<0.05 or P<0.01). The colonic content of 5-HT was significantly lower than that in the model group [(8.85 ± 0.53) ng/mg vs.(12.25 ± 1.95) ng/mg] ( P<0.01), the expression of SERT mRNA (0.85 ± 0.12 vs. 0.38 ± 0.02) and SERT protein (0.53 ± 0.11 vs. 0.36 ± 0.17) in the colon was significantly increased ( P<0.05 or P<0.01), the expression of SERT protein (0.88 ± 0.12 vs. 0.36 ± 0.13) in the hypothalamus was significantly increased ( P<0.05). Conclusion:Tongxie-Yaofang could relieve the visceral hypersensitivity, which may be achieved by regulating the 5-HT and SERT expression.
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Objective:To establish an ultra-performance liquid chromatography-mass spectrometry （UPLC-MS/MS） for determining the plasma concentrations of 10 active ingredients in Wujiwan at different time points after oral administration， and to compare the pharmacokinetic characteristics between normal rats and rats with chronic visceral hypersensitive irritable bowel syndrome （CVH-IBS）. Method:CVH-IBS rat model was prepared by the neonatal rat colon percutaneous transluminal coronary angioplasty （PTCA） balloon stimulation method. After intragastric administration of Wujiwan （0.245 g·kg<sup>-1</sup>）， blood was collected from the jugular vein at different time points， and the plasma concentrations of 10 active ingredients （berberine hydrochloride， palmatine hydrochloride， coptisine hydrochloride， jatrorrhizine hydrochloride， epiberberine， dihydroberberine， evodiamine， evodine， paeoniflorin， albiflorin） in Wujiwan was detected simultaneously by UPLC-MS/MS， the pharmacokinetic parameters of each component in normal rats and CVH-IBS rats were calculated. Result:The established UPLC-MS/MS could sensitively and accurately detect the plasma concentrations of 10 active ingredients of Wujiwan in rats. Compared with the normal group， the absorption rates of these 10 active ingredients of Wujiwan in the blood of CVH-IBS rats all decreased to a certain extent， and the peak time （<italic>t</italic><sub>max</sub>） was prolonged. Among them， the <italic>t</italic><sub>max</sub> of berberine hydrochloride and jatrorrhizine hydrochloride were significantly prolonged from 54 minute and 39 minute to 90 minute， respectively （<italic>P</italic><0.05， <italic>P</italic><0.01）. Area under the plasma concentration-time curve （AUC<sub>0-</sub><italic><sub>t</sub></italic>） of each component increased， and evodiamine and paeoniflorin were significantly different （<italic>P</italic><0.05，<italic> P</italic><0.01）. The clearance rates （CL/<italic>F</italic>） of these 10 active ingredients were all decreased， among which berberine hydrochloride， palmatine hydrochloride and evodiamine had significant differences （<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:There are significant differences in the pharmacokinetic behavior of the active ingredients in Wujiwan between normal rats and CVH-IBS rats， which may be related to the destruction of microstructure of intestinal epithelial cells and the change of activity of liver enzymes under the pathological state of IBS.
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Background: Visceral hypersensitivity is considered as a key pathophysiological mechanism involved in functional gastrointestinal disorders (FGIDs). Visceral nociception and hyperalgesia is existed extensively following exposure to post-traumatic stress disorder (PTSD), however, its molecular mechanism in intestinal tract is unclear. Aims: To explore the potential role of N-Myc downstream-regulated gene 2 (NDRG2) in intestinal tract for mediating visceral hypersensitivity following exposure to PTSD. Methods: PTSD model was established by single prolonged stress (SPS). SD rats were divided into normal control group, CTX group, PTSD group and PTSD+CTX group. Mice were divided into normal control group, PTSD group, NDRG2
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Visceral hypersensitivity is one of the pathogenesis of functional gastrointestinal disorders (FGIDs) including irritable bowel syndrome and functional dyspepsia. In recent years, more and more studies have suggested that the occurrence of gastrointestinal hypersensitivity is related to the changes of neuronal plasticity in the intestinal nervous system or afferent pathway, and potassium channels play a crucial role in controlling neuronal excitability. Lots of studies have shown that decreased expressions or activities of voltage-gated potassium channels, calcium-activated potassium channels, and two-pore domain potassium channels in nociceptors can increase the excitability of neurons, increase visceral pain, and participate in the occurrence of FGIDs. This article reviewed the research progress on relationship between potassium channels and visceral hypersensitivity.
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OBJECTIVE: To observe the effect of moxibustion on visceral pain, diarrhea, colonic 5-hydroxytryptamine (5-HT) content, and expression of tryptophan hydroxylase 1 (TPH1), serotonin reup take transporter (SERT) and 5-hydroxytryptamine receptor 3 (5-HT3R) in colon tissue of rats with diarrhea irritable bowel syndrome (IBS-D), so as to reveal its underlying mechanisms in treating IBS-D. METHODS: Thirty male SD rats were randomly divided into blank control, model and moxibustion groups (n＝10 rats in each group). The IBS-D model was established by chronic restraint combined with gavage of Senna leaf solution. Moxibustion was applied to bilateral "Tianshu" (ST25) and "Shangjuxu" (ST37) for 30 min, once a day for 7 days. After the treatment, the loose stool rate (number of loose stool/total number of feces granules X100%) and the minimum volume threshold of abdominal reflex (abdominal pain threshold) induced by rectal dilatation were observed. The content of colonic 5-HT was detected by using ELISA, and the expression of TPH1, SERT and 5-HT3R mRNAs and proteins were detected by using quantitative real time-PCR and Western blot, respectively. RESULTS: Compared with the blank control group, the minimum volume threshold of abdominal retraction reflex and the relative expression of SERT protein and mRNA were significantly decreased (P<0.01), and the loose stool rate, colonic 5-HT content, and relative expression of TPH1 and 5-HT3R proteins and mRNAs were notably increased in the model group (P<0.01). After moxibustion, both the decrease of minimum volume threshold and SERT protein and mRNA expressions and the increase of loose stool rate, colonic 5-HT content and TPH1 and 5-HT3R protein and mRNA expressions were reversed (P<0.01). CONCLUSION: Moxibustion of ST25 and ST37 can relieve abdominal hypersensitivity and diarrhea in IBS-D model rats, which is related to its effects in down-regulating colonic 5-HT content and expression of TPH1 and 5-HT3R proteins and mRNAs and in up-regulating expression of SERT protein and mRNA (regulating 5-HT/5-HT3R signaling)．.
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Background: The etiology and pathogenesis of irritable bowel syndrome (IBS) are not yet clear, and is lack of effective means for its prevention, diagnosis and treatment in clinic. In recent years, more and more studies showed that intestinal local mucosal immune dysfunction plays an important role in the pathogenesis of IBS. Aims: To investigate the role of intestinal dendritic cells (DC) in the imbalance of colonic mucosal Th1/Th2 immune response pathway in IBS with diarrhea (IBS-D) rats and its effect on visceral hypersensitivity. Methods: Forty-five adult SD rats were randomly divided into blank control group, NS control group and model group, and each group consisted of 15 rats. Visceral hypersensitive model was established by acetic acid enema combined with restraint stress. Abdominal withdrawal reflex (AWR) test and fecal characteristics were used to evaluate the visceral sensitivity. Flow cytometry separation technique was used to isolate DC from mesenteric lymph nodes and CD4
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Chronic pelvic pain is a common yet difficult problem to manage, plaguing the gynecologist as well as the gastroenterologist and general surgeon. Highlighted by increased visceral hypersensitivity, endometriosis and irritable bowel syndrome (IBS) are the most common causes or chronic unrelenting pelvic pain. Recently, the similarities between the two conditions has begged the question as to whether there is any common denominator between the two conditions and their likely co-existence and mismanagement. Further, the association of polycystic ovary syndrome (PCOS) in this cohort remains definitively uncharacterized. This report details a young female patient with the triad of POCS, IBS and endometriosis presenting with chronic pelvic pain.
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Background@#Irritable bowel syndrome (IBS), a functional gastrointestinal disorder, is characterized by cytokine imbalance. Previously, decreased plasma interleukin 10 (IL-10) level was reported in patients with IBS, which may be due to genetic polymorphisms. However, there are no reports correlating the IL-10 polymorphisms with IL-10 production in patients with IBS. This study aimed to analyze the effect of IL-10 polymorphisms on IL-10 production and its correlation with the clinical symptoms in Chinese patients with diarrhea-predominant IBS (IBS-D).@*Methods@#Two IL-10 single nucleotide polymorphisms (rs1800871 and rs1800896) were detected in 120 patients with IBS-D and 144 healthy controls (HC) using SNaPshot. IBS symptom severity score, Bristol scale, hospital anxiety, and depressive scale (HADS) were used to evaluate the clinical symptoms, as well as the psychological status and visceral sensitivity of the subjects. IL-10 levels in the plasma and peripheral blood mononuclear cell (PBMC) culture supernatant were measured using enzyme-linked immunosorbent assay, while those in ileal and colonic mucosal biopsies were measured using immunohistochemistry.@*Results@#The frequency of rs1800896 C allele was significantly lower in the patients with IBS-D than that in the HC (odds ratio: 0.49, 95% confidence interval: 0.27–0.92, P = 0.0240). The IL-10 levels in the plasma (P = 0.0030) and PBMC culture supernatant (P = 0.0500) of the CT genotype subjects were significantly higher than those in the TT genotype subjects. The CT genotype subjects exhibited a higher pain threshold in the rectal distention test than the TT genotype subjects. Moreover, IL-10 rs1800871 GG genotype subjects showed an increase in the HADS score compared to other genotype subjects.@*Conclusions@#IL-10 rs1800896 C allele is correlated with higher IL-10 levels in the plasma and the PBMC culture supernatant, which is associated with a higher pain threshold in the Chinese patients with IBS-D. This study provides an explicit relationship of IL-10 polymorphisms with IL-10 production, which might help in understanding the pathogenesis of IBS-D.
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Diarrhea-predominant irritable bowel syndrome (IBS-D) is not only a biological mental disorder, but also a kind of chronic functional bowel disease induced by many factors. The pathogenesis of IBS-D is related to visceral sensory abnormalities, intestinal dynamics abnormalities, intestinal mucosal micro-inflammatory reactions, heredity, dietary intolerance and other factors. The visceral hypersensitivity is one of the main pathophysiology, and refers to an unknown cause of intestinal hypersensitivity to cold, bad mood and other stimuli. However, its mechanism remains unclear. The pathogenesis of IBS-D is closely related to the disturbance of brain and intestinal interaction. IBS-D patients often suffer from anxiety, depression and other psychiatric symptoms due to repeated illness, but long-term chronic mental stress can induce and aggravate IBS-D visceral hypersensitivity. Brain-derived neurotrophic factor (BDNF) and its high-affinity receptor tyrosine kinase B (TrkB) are hotspots in studies about brain-gut axis. BDNF is a highly expressed cytokine in the central nervous system and gastrointestinal tract, and can promote the development of the nervous system, maintain the normal function of mature nerve cells and regulate the gastrointestinal motility and visceral sensitivity. Intestinal microbiota is the key link of brain-gut interaction. Mental disorders are closely related to intestinal symptoms caused by changes in intestinal microbial environment. Repeated mental stimulation can lead to changes in intestinal flora; on the other hand, changes in intestinal flora structure are closely related to the development of the nervous system and the function of the brain. With intestinal microbiota as the study object, this article mainly discusses the effect of intestinal microbiota in regulating visceral hypersensitivity of IBS-D based on brain-gut axis (BDNF/TrkB signaling pathway).
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Objective@#To investigate the effects of glutamate (Glu) injected into hypothalamic paraventricular nucleus (PVN) on visceral pain of chronic visceral hypersensitivity (CVH) rats and its possible mechanism.@*Methods@#Newborn SD rats were given CVH rat model by colorectal distension (CRD) on the 8th, 10th and 12th day after birth. Thirty rats with successful CVH model were randomly divided into CVH model group (CVH group), CVH + injection of saline into PVN group (NS group), CVH+ injection of Glu into PVN (3, 6, and 12 μg Glu, namely G3, G6, and G12, respectively), 6 rats in each group, and 6 SD rats with matching body mass were taken as sham operation group (Sham group). The pain behavior of the rats was evaluated by pain threshold, abdominal withdrawal reflex (AWR) score, and abdominal external oblique muscle electromyography (EMG). The expression of arginine vasopressin (AVP) and the proliferation of colon tissue were detected by immunohistochemical staining. The apoptosis of colon tissue was detected by TUNEL.@*Results@#Compared with the NS group, the pain thresholds of the G3, G6 and G12 groups increased, and the AWR scores and EMG amplitudes decreased. The differences were statistically significant(Pain threshold: t=7.65, 16.31, 24.78, both P<0.05; AWR scores: t=-2.98, -4.77, -7.29, both P<0.05; EMG amplitudes: t=-3.06, -5.75, -8.92, both P<0.05). Compared with the Sham group, the expression of AVP in PVN of the CVH group and NS group decreased ((42.63±5.20) %, (18.67±2.94) %, (17.53±2.47) %; t=6.95, t=7.56, both P<0.05). The expression of AVP was increased after different doses of Glu into PVN, and the AVP level in G12 group ((18.15±6.49)%) was higher than that of NS group, the difference was statistically significant (t=-4.21, P<0.05). Compared with the Sham group, the expression of PCNA in colonic mucosal cells of the CVH group and NS group decreased ((65.48±1.68) %, (18.39±1.67) %, (17.69±1.68) %; t=34.35, t=34.80, both P<0.05). The expression of PCNA was increased after different doses of Glu injected into PVN, and the PCNA level in G12 group ((59.91±5.63)%) was higher than that of NS group, the difference was statistically significant (t=-12.44, P<0.05). Compared with the Sham group, the expression of apoptotic cells in colonic mucosal cells of the CVH group and NS group increased ((23.38±11.40)%, (83.79±3.57)%, (80.91±2.47)%; t=-8.77, t=-8.54, both P<0.05). The expression of apoptotic cells was decreased after different doses of Glu into PVN, and the G12 group was ((18.15±6.49) %). Compared with NS group, the difference was statistically significant (t=15.65, P<0.05).@*Conclusion@#Injection of Glu into hypothalamic PVN can alleviate the visceral pain behaviors in CVH rats, and its mechanism may be related to arginine vasopressin.
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Objective To investigate the effects of glutamate (Glu) injected into hypothalamic pa-raventricular nucleus (PVN) on visceral pain of chronic visceral hypersensitivity (CVH) rats and its possi-ble mechanism. Methods Newborn SD rats were given CVH rat model by colorectal distension (CRD) on the 8th,10th and 12th day after birth. Thirty rats with successful CVH model were randomly divided into CVH model group (CVH group),CVH + injection of saline into PVN group (NS group),CVH+ injection of Glu into PVN (3,6,and 12 μg Glu,namely G3,G6,and G12,respectively),6 rats in each group,and 6 SD rats with matching body mass were taken as sham operation group (Sham group). The pain behavior of the rats was evaluated by pain threshold,abdominal withdrawal reflex (AWR) score,and abdominal external ob-lique muscle electromyography (EMG). The expression of arginine vasopressin (AVP) and the proliferation of colon tissue were detected by immunohistochemical staining. The apoptosis of colon tissue was detected by TUNEL. Results Compared with the NS group, the pain thresholds of the G3, G6 and G12 groups in-creased,and the AWR scores and EMG amplitudes decreased. The differences were statistically significant (Pain threshold:t=7. 65,16. 31,24. 78,both P<0. 05;AWR scores:t=-2. 98,-4. 77,-7. 29,both P<0. 05;EMG amplitudes:t=-3. 06,-5. 75,-8. 92,both P<0. 05). Compared with the Sham group,the expression of AVP in PVN of the CVH group and NS group decreased ((42. 63±5. 20) %,(18. 67±2. 94) %,(17. 53± 2. 47) %; t=6. 95,t=7. 56,both P<0. 05). The expression of AVP was increased after different doses of Glu into PVN,and the AVP level in G12 group ((18. 15±6. 49)%) was higher than that of NS group,the difference was statistically significant (t=-4. 21,P<0. 05). Compared with the Sham group,the expression of PCNA in colonic mucosal cells of the CVH group and NS group decreased ((65. 48±1. 68) %,(18. 39± 1. 67) %,(17. 69±1. 68) %;t=34. 35,t=34. 80,both P<0. 05). The expression of PCNA was increased after different doses of Glu injected into PVN,and the PCNA level in G12 group ((59. 91±5. 63)%) was higher than that of NS group,the difference was statistically significant (t=-12. 44,P<0. 05). Compared with the Sham group,the expression of apoptotic cells in colonic mucosal cells of the CVH group and NS group increased ((23. 38±11. 40)%,(83. 79± 3. 57)%,(80. 91± 2. 47)%;t=-8. 77,t=-8. 54,both P<0. 05). The expression of apoptotic cells was decreased after different doses of Glu into PVN,and the G12 group was ((18. 15±6. 49) %). Compared with NS group,the difference was statistically significant ( t=15. 65,P<0. 05). Conclusion Injection of Glu into hypothalamic PVN can alleviate the visceral pain be-haviors in CVH rats,and its mechanism may be related to arginine vasopressin.
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BACKGROUND/AIMS: The aim of present study is to estimate the effects of Melissa officinalis L. (MO) on visceral hypersensitivity (VH), defecation pattern and biochemical factors in 2 experimental models of irritable bowel syndrome (IBS) and the possible role of nitric oxide. METHODS: Two individual models of IBS were induced in male Wistar-albino rats. In the acetic acid model, the animals were exposed to rectal distension and abdominal withdrawal reflex, and the defecation patterns were determined. In the restraint stress model, the levels of TNF-α, myeloperoxidase, lipid peroxidation, and antioxidant powers were determined in the (removed) colon. Rats had been treated with MO, L-NG-nitroarginine methyl ester (L-NAME), aminoguanidine (AG), MO + AG, or MO + L-NAME in the mentioned experimental models. RESULTS: Hypersensitive response to rectal distension and more stool defecation in control rats have been observed in comparison to shams. MO-300 significantly reduced VH and defecation frequency in comparison to controls. VH and defecation pattern did not show significant change in AG + MO and L-NAME + MO groups compared to controls. Also, significant reduction in TNF-α, myeloperoxidase, thiobarbituric acid reactive substances (TBARS), and an increase in antioxidant power in MO-300 group was recorded compared to controls. AG + MO and L-NAME + MO groups showed a reverse pattern compared to MO-300 group. CONCLUSIONS: MO can ameliorate IBS by modulating VH and defecation patterns. Antioxidant and anti-inflammatory properties along with its effect on the nitrergic pathway seem to play important roles in its pharmacological activity.
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Animals , Humans , Male , Rats , Acetic Acid , Colitis , Colon , Defecation , Hypersensitivity , Irritable Bowel Syndrome , Lipid Peroxidation , Melissa , Models, Theoretical , NG-Nitroarginine Methyl Ester , Nitric Oxide , Peroxidase , Reflex , Thiobarbituric Acid Reactive SubstancesABSTRACT
Background:Cerebellar fastigial nucleus (FN)is involved in regulation of visceral activities such as cardiovascular, ingestion,respiratory,and acute gastric mucosal injury,yet it is unclear whether it participates in the regulation of visceral hypersensitivity and what is the possible mechanism. Aims:To investigate the effect and possible mechanism of glutamic acid (Glu ) injection into cerebellar FN on chronic visceral hypersensitivity in rats. Methods: Chronic visceral hypersensitivity rat model was established by neonatal colorectal distension (CRD). After 8 weeks,the rats were divided into CRD group,solvent group (0. 2 μL 0. 9% NaCl solution injection into cerebellar FN),high-,medium-,low-dose Glu groups (12,6,3 μg Glu injection into cerebellar FN,respectively),3-MPA +Glu group (12 μg Glu injection after glutamate decarboxylase inhibitor 3-MPA injection into cerebellar FN),Bic + Glu group (12 μg Glu injection into cerebellar FN after GABAAreceptor blocker Bic injection into lateral hypothalamic area). Pain threshold,abdominal withdrawal reflex (AWR)score and abdominal external oblique muscle electromyography (EMG)were used to detect visceral sensitivity,and malondialdehyde (MDA)content and superoxide dismutase (SOD)activity were measured. Results:Chronic visceral hypersensitivity rat model was successfully established. Compared with CRD group,pain threshold was significantly increased (P＜0. 05),AWR score,EMG amplitude,MDA content were significantly decreased (P＜0. 05 ),and SOD activity was significantly increased in a dose-dependent manner in Glu group (P ＜0. 05 ). Compared with 12 μg Glu group,pain threshold was significantly decreased (P＜0. 05),AWR score,EMG amplitude, MDA content were significantly increased (P ＜0. 05),and SOD activity was significantly decreased in 3-MPA +Glu group,Bic+Glu group (P＜0. 05). Conclusions:Glu injection into cerebellar FN can significantly reduce the visceral sensitivity in rats. The mechanism may be that Glu in cerebellar FN produces GABA via glutamate decarboxylase,and then binding GABAAreceptor in lateral hypothalamic area,resulting in increased intestinal mucosal antioxidant capacity, thereby reducing visceral hypersensitivity.
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PURPOSE: This study aimed to screen for differentially expressed microRNAs (miRNAs) in the colons of rats with visceral hypersensitivity to build the expression profiles of miRNAs therein and to determine the mechanism of Tongxieyaofang use in the treatment of irritable bowel syndrome (IBS). MATERIALS AND METHODS: Forty Sprague-Dawley rats were divided randomly into four groups: control group, model control group (induced by rectum stimulus and evaluated by abdominal withdraw reaction), treatment control group (normal saline), and Tongxieyaofang group (treated with Tongxieyaofang). We screened for differential expression of colonic mucosal miRNAs using liquid chip technology and verified the expression thereof using reverse transcription-PCR. RESULTS: The visceral hypersensitivity rat model was successfully established. We found the expression of let-7f, let-7i, miR-130b, miR-29a, miR-132, miR-21, and miR-375 to be up-regulated (p < 0.05), while the expression of miR-24, miR-31a, miR-192, miR-221, and miR-223 was down-regulated (p < 0.05) in the visceral hypersensitivity rats. After treatment with Tongxieyaofang, the expression of let-7f, let-7i, miR-130b, miR-29a, miR-132, miR-21, and miR-375 was reduced (p < 0.05), whereas the expression of miR-24, miR-31a, miR-192, miR-221, miR-223 was increased, compared to the treatment control group (p < 0.05). CONCLUSION: MiRNAs play a pivotal role in visceral hypersensitivity and might be targets in the treatment of IBS by Tongxieyaofang.
Subject(s)
Animals , Rats , Colon , Hypersensitivity , Irritable Bowel Syndrome , MicroRNAs , Models, Animal , Rats, Sprague-Dawley , RectumABSTRACT
ABSTRACT Objective: The aim of this study was to investigate the effects of acute physical and psychological stress and temporary central nucleus of the amygdala (CeA) block on stress-induced visceral hypersensitivity. Methods: Forty two male Wistar rats were used in this study. Animals were divided into 7 groups (n = 6); 1 - Control, 2 - physical stress, 3 - psychological stress, 4 - sham, 5 - lidocaine, 6 - lidocaine + physical stress and 7 - lidocaine + psychological stress. Stress induction was done using a communication box. Results: Abdominal withdrawal reflex (AWR) score was monitored one hour after stress exposure. AWR score significantly heightened at 20, 40 and 60 mmHg in the psychological stress group compared with control (p < 0.05), while, it was almost unchanged in other groups. This score was strikingly decreased at 20, 40 and 60 mmHg in lidocaine + psychological stress group compared with psychological stress with no tangible response on physical stress. Total stool weight was significantly increased in psychological stress group compared with control (0.72 ± 0.15, 0.1 ± 0.06 g) (p < 0.05), but it did not change in physical stress compared to control group (0.16 ± 0.12, 0.1 ± 0.06 g) (p < 0.05). Concomitant use of lidocaine with stress followed the same results in psychological groups (0.18 ± 0.2, 0.72 ± 0.15 g) (p < 0.05), while it did not have any effect on physical stress group (0.25 ± 0.1, 0.16 ± 0.12 g) (p < 0.05). Conclusions: Psychological stress could strongly affect visceral hypersensitivity. This effect is statistically comparable with physical stress. Temporary CeA block could also reduce visceral hypersensitivity post-acute psychological stress.
RESUMEN Objetivo: O objetivo desse estudo foi investigar os efeitos do estresse físico e psicológico agudo e bloqueio temporário do núcleo central da amídala (CeA) na hipersensibilidade visceral induzida por estresse. Métodos: Quarenta e dois ratos Wistar machos foram empregados nesse estudo. Os animais foram divididos em 7 grupos (n = 6): 1 - Controle, 2 - estresse físico, 3 - estresse psicológico, 4 - simulacro, 5 - lidocaína, 6 - lidocaína + estresse físico e 7 - lidocaína + estresse psicológico. A indução do estresse foi feita com o uso de uma caixa de comunicação. Resultados: O escore do reflexo de retirada abdominal (RRA) foi monitorado uma hora depois da exposição ao estresse. O escore RRA aumentou significativamente a 20, 40 e 60 mmHg no grupo de estresse psicológico versus controle (p < 0,05), enquanto que praticamente permaneceu inalterado nos demais grupos. Esse escore diminuiu drasticamente a 20, 40 e 60 mmHg no grupo de lidocaína + estresse psicológico versus estresse psicológico, sem resposta tangível no estresse físico. O peso total das fezes aumentou significativamente no grupo de estresse psicológico versus controle (0,72 ± 0,15, 0,1 ± 0,06 g) (p < 0,05), mas não houve mudança no grupo de estresse físico versus controle (0,16 ± 0,12, 0,1 ± 0,06 g) (p < 0,05). O uso simultâneo da lidocaína com o estresse acompanhou os mesmos resultados nos grupos psicológicos (0,18 ± 0,2, 0,72 ± 0,15 g) (p < 0,05), enquanto que não foi observado qualquer efeito no grupo de estresse físico (0,25 ± 0,1, 0,16 ± 0,12 g) (p < 0,05). Conclusões: O estresse psicológico pode afetar fortemente a hipersensibilidade visceral. Esse efeito é estatisticamente comparável com o estresse físico. Um bloqueio temporário do CeA também pode reduzir a hipersensibilidade visceral pós-estresse psicológico agudo.
Subject(s)
Animals , Rats , Stress, Psychological/complications , Viscera/physiopathology , Central Amygdaloid Nucleus/physiopathology , Hypersensitivity/physiopathology , Reflex, Abdominal/physiology , Rats, Wistar , Pain Perception/physiology , Central Amygdaloid Nucleus/metabolismABSTRACT
Objective Based on the observation of the changes of symptoms, histopathology, visceral sensitivity, mast cell activation, autophagy, and Beclin-1 and Claudin-2 expression in rats, we established and evaluated a new rat model of diarrhea-predominant irritable bowel syndrome (D-IBS) induced by restraint-stress combined with capsaicin (CAP) administration.Methods Forty healthy 5-week old male Sprague Dawley (SD) rats were randomly divided into normal group, model group I, model group II and model group III, with 10 rats in each group.The D-IBS model was established by restraint-stress combined with intragastric administration of CAP (2 mL/100 g body weight, 0.125% in group I, 0.250% in group II, 0.500% in group III), tail clipping and forelimb restriction for 30 minutes every day for 2 weeks.The rats in the control group were treated with saline for 2 weeks.The number of contraction of abdominal wall and arched back were measured by Power Lab instrument.The mast cell activation was detected using aldehyde-magenta-orange G staining.Light and electron microscopic examinations were performed to detect the morphology and autophagy of colonic tissues.The expressions of Beclin-1 and Claudin-2 in the colonic mucosa were detected by streptavidin-biotin complex (SABC) immunohistochemical staining.Results All rats in the model group III died during the experiment.Compared with the control group and model group I, the stool frequency was increased and the visceral sensitivity threshold decreased in the model group II, and there were statistically significant differences between the model group II and the control and model groups I (P < 0.05).The colonic mucosa, mucosal epithelium and glands in each group showed normal morphology and there was no submucosal vasodilatation and diffuse inflammatory cell infiltration.Except for the control group, round purple-reddish staining spots were observed in the rat mucosal stroma or submucosa in the model groups I and II, indicating an increased expression of mast cells.The autophagy, expressions of Beclin-1 and Claudin-2 in the colonic epithelium were significantly increased in the model group II compared with control group and model group I (P< 0.05).Conclusions The model of D-IBS induced by restraint-stress combined with capsaicin is characterized by increased diarrhea, visceral hypersensitivity, increased mast cell expression and autophagy of intestinal epithelial cells, and disruption of the intestinal mucosal barrier.This model is simple to set up and shows similar symptoms of human irritable bowel syndrome.Therefore, it is worthy of popularization and application.
ABSTRACT
Symptoms compatible with irritable bowel syndrome (IBS) such as abdominal pain and diarrhea may co exist in approximately one-third of patients with quiescent inflammatory bowel disease (IBD),so called IBS-like symptoms.These symptoms present as a clinical dilemma for management of IBD and diminish the patients' quality of life remarkably.IBS-like symptoms raise much concern in the research field of IBD in recent years.In this article,the latest research progress focusing on the prevalence,pathogenesis and management of IBS-like symptoms coexisting with quiescent IBD was reviewed.