Effects of psychological stress on small intestinal motility and bacteria and mucosa in mice

AIM: To investigate the effects of psychological stress on small intestinal motility and bacteria and mucosa in mice, and to explore the relationship between small intestinal dysfunction and small intestinal motility and bacteria and mucosa under psychological stress. METHODS: Sixty mice were randomly divided into psychological stress group and control group. Each group were subdivided into small intestinal motility group (n= 10), bacteria group (n = 10), and D-xylose administered to stomach group (n= 10). An animal model with psychological stress was established housing the mice with a hungry cat in separate layers of a two-layer cage. A semi-solid colored marker (carbon-ink) was used for monitoring small intestinal transit. The proximal small intestine was harvested under sterile condition and processed for quantitation for aerobes (Escherichia coli) and anaerobes (Lactobacilli). The quantitation of bacteria was expressed as Iog10(colony forming units/g). D-xylose levels in plasma were measured for estimating trie damage of small intestinal mucosa. RESULTS: Small intestinal transit was inhibited (39.80±9.50% vs 58.79±11.47%,P<0.01) in mice after psychological stress, compared with the controls. Psychological stress resulted in quantitative alterations in the aerobes (E.coli). There was an increase in the number of E coli in the proximal small intestinal flora (1.78±0.30 log10(CFU/g) vs 1.37±0.21 log10(CFU/g), P<0.01), and there was decrease in relative proportion of Lactobacilli and E.coli of stressed mice (0.53±0.63 vs 1.14±1.07,P<0.05), while there was no significant difference in the anaerobes (Lactobacilli) between the two groups (2.31±0.70 log10 (CFU/g) vs 2.44±0.37 log10(CFU/g), P>0.05). D-xylose concentrations in plasma in psychological stress mice were significantly higher than those in the control group (2.90±0.89 mmol/L vs 0.97±0.33 mmol/L, P<0.01). CONCLUSION: Small intestinal dysfunction under psychological stress may be related to the small intestinal motility disorder and dysbacteriosis and the damage of mucosa probably caused by psychological stress.     

小肠动力与影响因素的研究进展

小肠受特殊解剖位置以及检测手段的限制,小肠运动功能的研究相对滞后,尤其是对小肠MMC的病理生理功能缺乏全面的了解。研究证实小肠动力异常与细菌过度生长和慢传输性便秘等有关。十二指肠内酸和脂肪、葡萄糖的吸收对小肠动力均有影响。同时神经体液等因素对小肠动力也有调节作用。     

下食管括约肌压力与局部组织内一氧化氮和血管活性肠肽含量的关系

目的　研究下食管括约肌(LES)局部组织内一氧化氮(NO)和血管活性肠肽(VIP)含量与LES压力(LESP)的关系。方法　检测了108 例食管运动功能障碍性疾病患者LES局部组织内NO和VIP含量及LESP。结果　LESP与组织内NO和VIP含量呈负相关(r= - 90.7,P< 0.01;r= - 92.3,P< 0.01),NO和VIP含量之间呈正相关(r= 88.5,P< 0.01)。结论　胃食管反流性疾病(GERD)和贲门失弛缓症患者LES局部组织内NO和VIP含量异常,并且两者之间相互影响,相互作用,共同参与了LESP的调节和GERD及贲门失弛缓症的病理生理过程     

Simotang enhances gastrointestinal motility, motilin and cholecystokinin expression in chronically stressed mice

AIM:To investigate the effect of Simotang(Decoction of Four Powered Drugs) on gastrointestinal motility,motilin and cholecystokinin expression in chronically stressed mice.METHODS:Forty mice were randomly divided into control group,stress group(model group),mosapride group and Simotang group,10 in each group.A variety of unpredictable stimulations were used to induce chronic stress in mice.Then,the mice were treated with distilled water,mosapride or Simotang for 7 d.Gastric emptying and intestinal propulsio...     

Roles of sphincter of Oddi motility and serum vasoactive intestinal peptide,gastrin and cholecystokinin octapeptide

AIM:To investigate roles of sphincter of Oddi(SO)motility played in pigment gallbladder stone formation in model of guinea pigs.METHODS:Thirty-four adult male Hartley guinea pigs were divided randomly into two groups:the control group and pigment stone group.The pigment stone group was divided into 4 subgroups with 6 guinea pigs each according to time of sacrifice,and were fed a pigment lithogenic diet and sacrificed after 3,6,9 and 12wk.SO manometry and recording of myoelectric activity of the guinea pigs were obtained by multifunctional physiograph at each stage.Serum vasoactive intestinal peptide(VIP),gastrin and cholecystokinin octapeptide (CCK-8)were detected at each stage in the process of pigment gallbladder stone formation by enzyme-linked immunosorbent assay.RESULTS:The incidence of pigment gallstone formation was 0%,0%,16.7%and 66.7%in the 3-,6-,9-and 12-wk group,respectively.The frequency of myoelectric activity decreased in the 3-wk group.The amplitude of myoelectric activity had a tendency to decrease but not significantly.The frequency of the SO decreased significantly in the 9-wk group.The SO basal pressure and common bile duct pressure increased in the 12-wk group(25.19±7.77 mmHg vs 40.56±11.81 mmHg,22.35±7.60 mmHg vs 38.51±11.57mmHg,P<0.05).Serum VIP was significantly elevated in the 6-and 12-wk groups and serum CCK-8 was decreased significantly in the 12-wk group.CONCLUSION:Pigment gallstone-causing diet may induce SO dysfunction.The tension of the SO increased.The disturbance in SO motility may play a role in pigment gallstone formation,and changes in serum VIP and CCK-8 may be important causes of SO dysfunction.     

Small intestinal bacteria overgrowth decreases small intestinal motility in the NASH rats

AIM： To explore the relationship between small intestinal motility and small intestinal bacteria overgrowth （SIBO） in Nonalcoholic steatohepatitis （NASH）, and to investigate the effect of SIBO on the pathogenesis of NASH in rats. The effect of cidomycin in alleviating severity of NASH is also studied.
METHODS： Forty eight rats were randomly divided into NASH group （n = 16）, cidomycin group （n = 16） and control group （n = 16）. Then each group were subdivided into small intestinal motility group （n = 8）, bacteria group （n = 8） respectively. A semi-solid colored marker was used for monitoring small intestinal transit. The proximal small intestine was harvested under sterile condition and processed for quantitation for aerobes （E. coli and anaerobes （Lactobacilli）. Liver pathologic score was calculated to qualify the severity of hepatitis. Serum ALT, AST levels were detected to evaluate the severity of hepatitis.
RESULTS： Small intestinal transit was inhibited in NASH group （P 〈 0.01）. Rats treated with cidomycin had higher small intestine transit rate than rats in NASH group （P 〈 0.01）. High fat diet resulted in quantitative alterations in the aerobes （E. coli） but not in the anoerobics （Lactobacill）. There was an increase in the number of E. coli in the proximal small intestinal flora in NASH group than in control group （1.70 ± 0.12 log10 （CFU/g） vs 1.28 ± 0.07 log10 （CFU/g）, P 〈 0.01）. TNF-α concentration was significantly higher in NASH group than in control group （1.13 ± 0.15 mmol/L vs 0.57 ± 0.09 mmol/L, P 〈 0.01）. TNF-α concentration was lower in cidomycin group than in NASH group （0.63 ± 0.09 mmol/L vs 1.13 ± 0.15 mmol/L, P 〈 0.01）. Treatment with cidomycin showed its effect by significantly lowering serum ALT, AST and TNF-α levels of NASH rats.
CONCLUSION： SIBO may decrease small intestinal movement in NASH rats. SIBO may be an important pathogenesis of Nash. And treatment with cidomycin by mouth can allevi     

血管活性肠肽与消化系疾病的研究进展

血管活性肠肽(vasoactive intestinal polypeptide,VIP)既是胃肠激素,又是神经肽,是一种重要的脑肠肽,他涉及生理、生化、细胞生物学、分子生物学、神经学科、免疫学等多种学科.在肝脏、胆道、胰腺、胃肠道等均有分布,与消化系疾病有着密切的关系.在体内病理的循环状态中,VIP降解缓慢,其含量及受体敏感性一旦发生变化,会导致多系统疾病的发生,尤其引起消化系疾病分泌功能的紊乱.本文从VIP生物学特性、功能以及与消化系疾病的关系等方面作一概述.     

Role of vasoactive intestinal peptide and nitric oxide in the modulation of electroacupucture on gastric motility in stressed rats

INTRODUCTION In recent years, along with the extensive research into enteric nerve system (ENS), increasing evidence shows that peptidergic neurotransmitters are the key factors regulating the gastric motility. Our previous research[1-3] showed that electroacupucture (EA) at acupoints of the Stomach Meridian of Foot-Yangmin may regulate gastric movement, increase blood flow in the microvessels in the gastric mucosa, and exert a protective effect on gastric mucosa. Nitric oxide (NO) an…     

Oddi括约肌功能障碍患者乳头局部组织中血管活性肠肽和一氧化氮的改变及其意义

目的　探讨血管活性肠肽 (VIP)和一氧化氮 (NOS)在Oddi括约肌功能障碍发病机制中的作用。方法　选择 68例因不明原因的上腹痛、黄疸而进行逆行胰胆管造影及乳头括约肌切开术的患者 ,采用内镜下活检 ,钳取乳头黏膜、Oddi括约肌及胆管内壁组织各 1块。标本常规石蜡包埋 ,连续切片 ,免疫组化链酶亲和素 过氧化物酶法 (SABC法 )观察乳头组织内VIP及NOS的变化。将 68例患者分为Oddi括约肌功能障碍组 (SOD组 )与非Oddi括约肌功能障碍组 (非SOD组 )。结果　SOD患者乳头黏膜及Oddi括约肌内VIP和NOS含量明显减少 (P <0 .0 5 ) ,VIP和NOS含量呈正相关关系 (r =0 .87,P <0 .0 1)。结论　乳头局部组织中VIP和NOS的表达明显降低。VIP和NOS的减少可能在SOD的发生机制中具有一定的作用     

Effect of fluoxetine on depression-induced changes in the expression of vasoactive intestinal polypeptide and corticotrophin releasing factor in rat duodenum

AIM： To investigate changes in vasoactive intestinal polypeptide （VIP） and corticotrophin releasing factor （CRF） in the plasma and duodenum of chronic stressinduced depressed rats and the effects of fluoxetine hydrochloride （fluoxetine） treatment on depressioninduced changes in VIP and CRF. METHODS： A Sprague-Dawley rat model of chronic stress-induced depression was produced. Thirty experimental rats were randomly divided into the following groups： control group, saline-treated depressed group, and fluoxetine-treated depressed group. Openfield testing was performed to assess the rats＇ behavior. VIP and CRF levels in plasma were measured by ELISA. Immunofluorescence techniques combined with laser scanning confocal microscopy （LSCM） were used to investigate VIP and CRF expression in the duodenum. RESULTS： The open-field behavior, both crossing and rearing, of depression model rats, decreased significantly compared with those of normal control rats over 5 min. Defecation times increased significantly. Compared to the control group, FITC fluorescence of duodenal CRF expression and plasma CRF levels in the depressed rats increased significantly （fluorescence intensity of duodenal CRF： 11.82 ± 2.54 vs 25.17 ± 4.63; plasma CRF： 11.82 ±2.54 ng/L vs 25.17 ± 4.63 ng/L, P 〈 0.01）, whereas duodenal VIP expression and plasma VIP levels decreased significantly （fluorescence intensity of duodenal VIP： 67.37 ± 18.90 vs 44.51 ± 16.37; plasmaVIP： 67.37 ±18.90 ng/L vs 44.51 ± 16.37 ng/L, P 〈 0.01）. Fluoxetine improved depressed behavior, increased VIP expression and decreased CRF expression in plasma and the duodenal tissue of depressed rats. CONCLUSION： Chronic stress can induce injury to the duodenum, accompanied by increasing CRF and decreasing VIP in the plasma and duodenum. Treatment with fluoxetine can ameliorate pathological changes in the duodenum of depressed rats, which suggests that antidepressants are an effective therapeutic agent for some duodenal diseases caused     

Effect of psychological stress on gastric motility assessed by electrical bio-impedance

AIM: To evaluate gastric motility using electrical bio-impedance (EBI) and gastric changes as a result of stress induced by psychological tests.METHODS: A group of 57 healthy women, aged 40-60 years, was recruited, and a clinical history and physical examination were performed. The women were free from severe anxiety, chronic or acute stress, severe depression, mental diseases and conditions that affect gastric activity. The women were evaluated under fasting conditions, and using a four-electrode configuration, the gastric signals were obtained through a BIOPAC MP-150 system. The volunteers were evaluated using the following paradigm: basal state, recording during the Stroop Test, intermediate resting period, recording during the Raven Test, and a final resting period. We analyzed the relative areas of the frequency spectrum: A1 (1-2 cpm), A2 (2-4 cpm), A3 (4-8 cpm), and A4 (8-12 cpm), as well as the median of area A2 + A3. The data were analyzed by an autoregressive method using a Butterworth filter with MatLab and Origin. Analysis of variance (ANOVA) and Friedman ANOVA (for nonparametric variables) were performed; in addition, pairs of groups were compared using the T dependent and Wilcoxon T tests.RESULTS: The results of the main values of area A2 were not significantly different comparing the five steps of the experimental paradigm. Nevertheless, there was a tendency of this A2 region to decrease during the stress tests, with recuperation at the final resting step. When an extended gastric region was considered (1-4 cpm), significant differences with the psychological stress tests were present (F = 3.85, P = 0.005). The A3 region also showed significant changes when the stress psychological tests were administered (F = 7.25, P < 0.001). These differences were influenced by the changes in the adjacent gastric region of A2. The parameter that we proposed in previous studies for the evaluation of gastric motility by electrical bio-impedance (EBI) was the median of the area under the region from 2 to 8 cpm (A2 + A3). The mean values of these frequencies (median of the A2 + A3 area) with the stress test showed significant changes (F = 5.5, P < 0.001). The results of the Wilcoxon T test for the A4 area parameter, which is influenced by the breathing response, changed significantly during the Raven stress test (P < 0.05).CONCLUSION: We confirm that the gastric response to acute psychological stress can be evaluated by short-term EBI.     

Distribution of vasoactive intestinal polypeptide and substance P receptors in human colon and small intestine

Vasoactive intestinal polypeptide (VIP) and substance P are found in neurons in the lamina propria and submucosa and muscularis propria of human small intestine and colon. VIP receptors coupled to adenylate cyclase are present on epithelial, smooth muscle, and mononuclear cells. This study analyzes the distribution of[¹²⁵I]VIP binding and [¹²⁵]substance P in human colon and small intestine using autoradiographic techniques. [¹²⁵I]VIP binding was present in high density in the mucosal layer of colon and small intestine. [¹²⁵I]VIP binding was not significantly greater than nonspecific binding in smooth muscle layers or the lymphoid follicles. In contrast, [¹²⁵I]substance P binding was present in high density over the colonic muscle but was not present over the mucosal layer. In human colon cancer, [¹²⁵I]VIP grain density over the malignant tissue was only slightly higher than background. These autoradiographic studies of [¹²⁵I]VIP binding indicate that the highest density of VIP receptors was found in the small intestine and superficial colonic mucosa, whereas the density of substance P receptors was highest over the smooth muscle layers. These findings suggest a mismatch between immunochemical content of the peptide and autoradiographic density of the receptor.This work was supported by funds from the Research Service of the Veterans Administration.     

Vasoactive intestinal polypeptide appears to be one of the mediators in misoprostol-enhanced small intestinal transit in rats

BACKGROUND AND AIMS: Prostaglandin analogs have the pharmacologic effect of speeding up small intestinal transit (SIT). It remains unknown whether some gut peptides also mediate this enhancement. We studied the effect of misoprostol on rat SIT and looked at the role of vasoactive intestinal polypeptide (VIP) release during its action. METHODS: A group of rats initially received oral misoprostol treatment of 1, 10, 50 and 100 microg/kg, respectively. By using orally fed charcoal as a motility marker, the SIT was assessed at 30 min following oral misoprostol treatment. Another group of rats received misoprostol as an intraperitoneal injection in similar doses to the group above. The small intestinal transit was computed for this group at 30 min following misoprostol injection via an instilled radiochromium motility marker that went through a previously placed intraduodenal catheter. The plasma VIP level was measured by using a radioimmunoassay kit. RESULTS: Neither charcoal evaluated transit nor the plasma VIP level was influenced by the lower doses of oral misoprostol treatment (1 and 10 microg/kg), whereas other doses enhanced SIT and diminished the plasma VIP level (P< 0.01).The similar effects on radiochromium computed SIT (P< 0.01) and plasma VIP levels were obtained in tubed rats following misoprostol intraperitoneal treatment. The SIT results correlated negatively with plasma VIP levels. CONCLUSIONS: Enhanced SIT and diminished VIP levels are found in rats following misoprostol treatment. It appears that inhibited VIP release is one of the mechanisms in misoprostol-enhanced SIT.     

Vasoactive intestinal polypeptide concentrations in heart atria of hypothyroid rats

OBJECTIVES:

To determine putative effects of various protocols of propylthiouracil (PTU)-induced hypothyroidism on vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI) levels in the atria of developing and adult female rats.

ANIMALS AND METHODS:

Perinatal hypothyroidism was induced by treating pregnant rats with 0.05% PTU in drinking water from late gestation till the age of 60 days (P-PTU). Adult rats were given PTU for 10, 30 or 70 days (PTU-10, PTU-30 and PTU-70, respectively). Corresponding age-matched controls were left intact (P-Cont, Cont-10, Cont-30 and Cont-70, respectively). Resting heart rate, serum total thyroxine concentration, body weight and atrial weight were determined in all animals. VIP-LI levels in tissue extracts were measured by radioimmunoassay.

RESULTS:

The values of heart rate, serum total thyroxine, body weight and atrial weight showed that 10-day treatment did not suppress thyroid gland function completely. However, the remaining experimental protocols were sufficient to reach stable hypothyroid conditions. Thyroid hormone deficiency led to a significant increase in VIP-LI levels in both atria of PTU-30 and PTU-70 rats (P<0.01 versus corresponding controls). Interestingly, in P-PTU atria, VIP-LI reached significantly higher values than in rats treated with PTU for the same time during adulthood (PTU-70).

CONCLUSIONS:

These results provide new evidence that hypothyroidism interferes with VIP-ergic innervation in rat heart atria. The impact of thyroid hormone deficiency on VIP-LI levels differed in P-PTU and PTU-70 rats suggesting that thyroid hormone may play an important part in the development of VIP-ergic innervation in rat heart atria.     

Effects of prostaglandins E2 and 552-01552-01552-01on motility of small intestine in man

Interdigestive motility of the small intestine was examined in 23 fasted healthy volunteers following luminal administration of the prostaglandins E₂ and F₂. Motility was monitored by means of water-perfused catheters measuring intraluminal pressure changes. The registration points were located 25 cm apart, in the proximal duodenum, at the angle of Treitz, and in the jejunum. Prostaglandin E₂ administered intraduodenally delayed the initiation of the subsequent activity front. The interval to the next activity front was prolonged by a dose of 1.0 mg prostaglandin E₂ from 79.5±9.5 min to 137.1±5.0 min (P<0.01) and to 158.0±14.0 min by 2.0 mg prostaglandin E₂ (P<0.05). Also, in four of seven experiments, a progressing activity front was arrested by 2.0 mg prostaglandin E₂. Prostaglandin F₂ at 2.5 or 5.0 mg given intraduodenally induced bursts of contractions with a frequency of 17.7± 0.8 contractions per minute and an amplitude of 10 to 110 mm Hg (P<0.07). In comparison, food intake produced irregular contractions at a frequency of 5.3± 1.8 contractions per minute and an amplitude of 10 to 50 mm Hg (P<0.05). It is concluded that prostaglandin E₂ delays the initiation of activity fronts in the duodenum. In contrast, prostaglandin F₂ changes the interdigestive motility pattern to one of intense contractile activity, which is different from the postprandial motility pattern.     

电针对胃动力紊乱大鼠血管活性肠肽表达的影响

[目的]探讨电针调整胃动力与血管活性肠肽(VIP)的内在联系.[方法]采用浆膜法测定胃电数据,放射和免疫组化方法观察针刺足三里穴对束缚冷应激致胃动力紊乱大鼠VIP表达的影响.[结果]与正常组比较,束缚冷应激大鼠胃运动频率和波幅升高(P＜0.01);与模型组比较,电针足三里穴可降低胃运动频率和波幅(P＜0.01),同时可影响VIP的表达(P＜0.05,＜0.01).[结论]VIP参与了电针对胃动力的调整作用.     

肠型胃腺癌及不典型增生组织中血管活性肠肽mRNA表达的研究

目的　血管活性肠肽 (VIP)与肿瘤关系密切 ,VIP可促进和 /或抑制一些肿瘤生长 ,而且一些肿瘤细胞有VIP的自分泌调节作用。VIP对胃癌生长的影响 ,胃癌细胞是否分泌VIP及存在VIP自分泌调节作用尚有争议。研究肠型胃腺癌及不典型增生组织中VIPmRNA的表达情况 ,试图探讨VIP在胃腺癌发生发展中的作用。方法　通过RT PCR方法 ,检测 1 5例正常胃窦黏膜、1 6例不典型增生胃黏膜及 2 0例肠型胃腺癌组织中VIPmRNA的表达量 ,通过与恒定表达的β actin(内参照 )mRNA表达量比较 ,计算出VIPmRNA与 β actinmRNA表达量的积分光密度比值 (V/B) ,以V/B值反映各组织中VIPmRNA表达量的高低。结果　肠型胃腺癌组织中V/B值明显高于不典型增生胃黏膜及正常胃窦黏膜 ,其V/B值分别为 :1 .452 2± 0 .32 82 ,0 .962 3± 0 .2 2 5 0 ,0 .951 3± 0 .2 66 9,差异有非常显著性 (P<0 .0 1 )。正常胃窦黏膜与不典型增生胃黏膜中 ,V/B值的差异无显著性 (P >0 .0 5)。结论　肠型胃腺癌组织VIPmRNA表达量明显高于不典型增生胃黏膜 ;VIP可能在肠型胃腺癌的发生发展中起重要的作用。     

Effects of intestinal mucosal blood flow and motility on intestinal mucosa

AIM:To investigate the role of intestinal mucosal blood flow(IMBF) and motility in the damage of intestinal mucosal barrier in rats with traumatic brain injury.METHODS:Sixty-four healthy male Wistar rats were divided randomly into two groups:traumatic brain injury(TBI) group(n = 32),rats with traumatic brain injury;and control group(n = 32),rats with sham-operation.Each group was divided into four subgroups(n = 8) as 6,12,24 and 48 h after operation.Intestinal motility was measured by the propulsion ratio o...     

The effect of acute hyperglycaemia on small intestinal motility in normal subjects

Summary The effects of hyperglycaemia on postprandial small intestinal motor activity are unclear. Duodenal and jejunal pressures and duodeno-caecal transit were measured in eight healthy male volunteers during euglycaemia (blood glucose 4–6 mmol/l) and hyperglycaemia (blood glucose 12–15 mmol/l). Duodenal and jejunal pressures were recorded with a manometric assembly during intraduodenal infusion of 100 ml nutrient liquid comprising 14% protein, 31.5% fat and 54.5% carbohydrate together with 15 g lactulose. Duodeno-caecal transit was determined by a breath hydrogen technique. The number of duodenal (p<0.05) and jejunal (p<0.01) pressure waves, excluding phase III episodes was reduced during hyperglycaemia compared to euglycaemia. Hyperglycaemia was associated with earlier onset of phase III activity (30±12 vs 132±20 min; p<0.05). Duodeno-caecal transit was slower during hyperglycaemia when compared to euglycaemia (114±17 vs 49±6 min, p<0.01). We conclude that induced hyperglycaemia has major effects on postprandial small intestinal motility. The reduction in duodenal and jejunal motor activity is likely to explain the retardation of small intestinal transit during hyperglycaemia.Abbreviations TMPD Transmusocal potential difference - MMC migrating myoelectric complex