Sweet food improves chronic stress-induced irritable bowel syndrome-like symptoms in rats

AIM: To investigate whether palatable sweet foods have a beneficial effect on chronic stress-induced colonic motility and inflammatory cytokines.METHODS: Adult male rats were divided into 3 groups: control (CON, n = 5), chronic variable stress with chow (CVS-A, n = 6), and chronic variable stress with chow and sweet food (CVS-B, n = 6). The rats were fed standard rodent chow as the chow food and/or AIN-76A as the sweet food. A food preference test for AIN-76A was performed in another group of normal rats (n = 10) for twelve days. Fecal pellet output (FPO) was measured for 6 wk during water bedding stress in the CVS groups. The weight of the adrenal glands, adrenocorticotropic hormone (ACTH) and corticosterone levels in plasma were measured. The expression levels of transforming growth factor-β, interleukin (IL)-2, and interferon-gamma (IFN-γ) were measured in the distal part of colonic tissues and plasma using Western blot analysis.RESULTS: In sweet preference test, all rats initially preferred sweet food to chow food. However, the consumption rate of sweet food gradually decreased and reduced to below 50% of total intake eight days after sweet food feeding. Accumulated FPO was higher in the CVS-A group compared with the CVS-B group over time. All stress groups showed significant increases in the adrenal to body weight ratio (CVS-A, 0.14 ± 0.01; CVS-B, 0.14 ± 0.01) compared with the control group (0.12 ± 0.01, P < 0.05). The plasma corticosterone and ACTH levels were significantly higher in the CVS-A (537.42 ± 32.95, 44.44 ± 6.54 pg/mL) and CVS-B (655.07 ± 30.82, 65.46 ± 4.44 pg/mL) groups than in the control group (46.96 ± 13.29, 8.51 ± 1.35 pg/mL, P < 0.05). Notably, the ratio of corticosterone to ACTH was significantly increased in the CVS-A group only. Rats exposed to CVS displayed significantly increased expression of IL-2 and IFN-γ in the plasma and distal colon compared to the control group, whereas this effect was significantly attenuated in the CVS-B group.CONCLUSION: These results suggest that concurrent sweet food ingestion during CVS might have an effect on the reduction of stress-induced colonic hyper-motility and pro-inflammatory cytokine production in rats.     

Evaluation in rats of the dose-response relationship among colonic mucosal growth,colonic fermentation,and dietary fiber

The dose-response relationship among dietary fiber, colonic fermentation, fecal weight, and mucosal growth were evaluated in this study. The morphometric parameter of total mucosal volume was used to assess diet-induced differences in colonic mucosal growth. Dietary fibers with a wide range of fermentability and that have previously been shown to inhibit the development of colonic neoplasia in rats were used. Sprague-Dawley rats were fed Purina Rodent Chow, AIN-76a fiber-free diet, or an AIN-76a diet supplemented with three different dietary fibers, (cellulose, guar gum, or wheat bran) at 2, 5, 10, or 15% of the diet. Diets were fed for 28 days. Total colonic mucosal volume was determined using sterologic principles and computerized image analysis; 48-hr fecal weight was measured; and the concentration of short-chain fatty acids (SCFA) in colonic contents was determined at study termination. Each type of fiber induced a dose-dependent increase in total mucosal volume of the colon and fecal weight. Mucosal volume and fecal weight were closely correlated (R ²>0.95). Total mucosal volume was not correlated with the concentration of total SCFA or butyrate in the colon. These results indicate that diet-induced change in colonic mucosal growth, as measured by total mucosal volume, is positively correlated with fecal weight and not related to alterations in colonic fermentation. Enhanced colonic mucosal growth occurs in rats fed dietary fibers that have previously been shown to inhibit the development of genotoxin-induced colonic neoplasia in rats.     

Effect of the dietary fibre content of lifelong diet on colonic cellular proliferation in the rat.

The effect of the fibre content of lifelong (18 months) diets on proximal and distal colonic cellular proliferation and short chain fatty acid (SCFA) content was investigated in 40 rats. Rats were fed a low fibre diet (17 g/kg non-starch polysaccharides NSP) or the stock diet (133 g/kg NSP). The higher fibre fed rats had increased caecal and colonic total contents (p < 0.001) and SCFAs than the low fibre fed rats (caecal SCFAs: higher fibre rats 96.4 (6.8) mumol/g wet weight v low fibre 22.7 (3.0): p < 0.001, colonic SCFAs: higher fibre 52.3 (3.1) mumol/g wet weight v low fibre 6.9 (2.2) mumol/g wet weight: p < 0.001). Cellular proliferation was increased in the proximal colon (bromodeoxyuridine labelling index, higher fibre 9.3 v low fibre 8.4 p < 0.05; flow cytometry, % cells in S phase higher fibre diet 7.9 v low fibre 6.9; p < 0.01) and there was a shift of proliferating cells to a higher region in each crypt. There was no significant difference in the percentage of cells in S phase in the distal colon of rats in both diet groups. The proliferative zone, however, was expanded in the distal colon of the higher fibre diet fed rats. This study indicates that long term higher fibre intake in rats is associated with a modest increase in cellular proliferation in the proximal colon but not the distal colon.     

Effect of chronic feeding of ethanol diet of “average” fat content on rat pancreas

The present study was done to determine the influence of dietary fat on the effect of ethanol on pancreatic macromolecular content and secretion. Weight-matched groups of Sprague-Dawley rats were divided into controls fed Rodent-Blox ad libitum; American Institute of Nutrition-76 (AIN-76) diet containing 12% calories as fat with 36% of carbohydrate calories replaced with 5% (weight/volume) concentration of ethanol fed ad libitum pair fed with animals given isocaloric amounts of AIN-76 diet for three to six months. Compared with Rodent-Blox fed controls, tissue content of trypsinogen, chymotrypsinogen, amylase, and lipase; specific activity and concentration of trypsinogen, chymotrypsinogen; and concentration of amylase were decreased at six months in AIN-76 fed controls. These changes did not result from diminished food intake, but were due to adaptation to the liquid diet. Animals fed AIN-76 diet plus ethanol did not show significant difference in the total content, specific activity, concentration, and secretion of digestive enzymes compared with those animals pair fed isocaloric amounts of AIN-76 diet. Activation of trypsinogen by exogenous trypsin was lower in rats fed AIN-76 diet and a similar change was observed in animals fed AIN-76 diet with ethanol for six months. These findings are in contrast to increased secretion of proteases and decreased trypsin inhibitor observed previously in animals fed ethanol in a diet containing "high" fat. These data indicate that ethanol effect on the pancreas is modified by dietary intake of fat and/or carbohydrates.     

Patient age and duration of colonoscopy are predictors for adenoma detection in both proximal and distal colon

AIM: To investigate the relation of patient characteristics and procedural parameters to the endoscopic detection rate of colonic adenomas. Further to study,which factors may be capable to predict the localization of adenomatous lesions.METHODS: We used the data base of a prospective randomized colonoscopy study(The Colo Cap trial) to identify patients being diagnosed with colon adenoma. Logistic regression analysis was conducted to reveal predictors for adenoma detection in the entire colon and also with respect to the proximal and distal part. Covariates including age, gender, duration of colonoscopy and comorbidities were defined to determine association between predictors and adenoma detection.RESULTS: Equal numbers of adenomas were detected in the proximal and distal side of the splenic flexure [126(57%) vs 94(43%), P = 0.104]. Simultaneous occurrence of adenomas in both sides of the colon was rare. The appearance of both proximal and distal adenoma was associated with increasing age(P = 0.008 and P = 0.024) and increasing duration of colonoscopy(P < 0.001 and P = 0.001). Male gender was a predictor for adenoma detection in the proximal colon(P = 0.008) but statistical significance was slightly missed with respect to the distal colon(P = 0.089). Alcohol abuse was found to be a predictor for the detection of distal adenoma(P = 0.041). CONCLUSION: Increasing age and longer duration of colonoscopy are factors with a strong impact on adenoma detection both in the proximal and distal colon. Since proximal adenomas occurred in absence of distal adenomas, complete colonoscopy should be performed for screening.     

Inhibitory effect of calcium on carcinogenesis at the site of colonic anastomosis

PURPOSE: A study was made to assess the effect of oral calcium supplementation on colorectal carcinogenesis at the colocolic suture line and in the rest of the colon following administration of a carcinogen. METHODS: Fifty-nine rats were randomly divided into two groups: control (given a standard diet for rats and mice containing 0.8 percent calcium) and treatment (given the same diet as before but with 2 percent calcium). Carcinogenesis was induced by 26 weekly injections of 1,2-dimethylhydrazine. All animals were subjected to an end-to-end colonic anastomosis at the beginning of the experiment using five stitches of steel wire. RESULTS: The control group developed significantly more tumors per animal at both the anastomosis ( P < 0.001) and in the rest of the colon ( P <0.001). In addition, the percentage of rats with tumors was significantly higher in the control group at both the anastomosis (chi-squared=12; df=1,P <0.001) and in the rest of the colon (chisquared=7.12; df=1,P <0.01). The mean surface of tumors was likewise greater in the control group at the anastomosis ( P <0.001) and throughout the rest of the colon ( P <0.001). Finally, there were significantly more small-bowel tumors (excluding the duodenum) in the control group ( P <0.05). CONCLUSIONS: It is concluded that calcium supplementation decreases the tumor yield at the site of end-to-end colonic anastomosis and in the rest of the colon and small bowel (excluding the duodenum).     

Adjuvant radiotherapy and anastomosis in rectal cancer—disturbing evidence from animal studies

PURPOSE: Adjuvant radiotherapy is used increasingly in the management of rectal cancer. However, ionizing radiation is mutagenic, and, superimposed on a background of increased cellular proliferation as seen around anastomoses and in colorectal cancer patients, there is the potential for enhanced metachronous cancer risk. METHOD: The influence of preoperative irradiation on both carcinogenesis and cellular proliferation at colonic anastomoses was explored in 180 adult male F344 rats. Orthovoltage x-rays were delivered to the distal descending colon by parallel opposed fields. Ninety rats received 16 Gy in one fraction; the remainder received 36 Gy in two fractions one week apart. In each irradiation group 18 rats either acted as controls or one week after radiotherapy underwent distal colotomy and repair. RESULTS: We found the descending colon susceptible to radiation carcinogenesis; 26 colorectal tumors developed in the low-dose irradiation group and 47 in the highdose group (P=0.0008; Mann-Whitney U test, 16 vs. 36 Gy). Preferential tumor development was seen in the anastomotic region. In those animals that underwent surgery and irradiation, among the low-dose irradiation group only 3 of 72 had tumors within the descending colon compared with 21 of 72 at the anastomotic site (McNemar's test chi-squared=40.9; P<0.001), and in the high-dose irradiation group 5 of 72 had tumors within the descending colon compared with 36 of 72 at the anastomotic site (McNemar's test chi-squared=22.0; P<0.001). Anastomotic crypt cell production rates were increased for at least three months following exposure to irradiation (16 Gy: f=15.1,P<0.005; 32 Gy: f=9.4,P<0.005). CONCLUSIONS: Radiation carcinogenesis is greatly enhanced at colonic anastomoses and may result from altered anastomotic proliferation. This has potentially disturbing implications in view of the increasing use of adjuvant radiotherapy for rectal carcinoma.     

Colonic mucosal atrophy induced by a liquid elemental diet in rats

The weight, the total crypt cell population, and the proliferation parameters of the colon were estimated in rats during a 4-week administration of a liquid elemental diet (Vivonex^® standard). Both mitotic and DNA synthesis activity were decreased (P<0.01) in the colonic mucosa during the administration of the diet. The weight of the colon was electively decreased (P<0.01) from the first week of the treatment. After four weeks, a 75% decrease in the cell population of mucosal glands was observed. This showed that considerable atrophy of the colonic mucosa occurred under the effect of feeding the elemental diet. This atrophy was probably mediated by a reduction in the proliferative activity of the stem cells in the mucosal glands.     

Regulatory Mechanism of Electroacupuncture in Irritable Bowel Syndrome: Preventing MC Activation and Decreasing SP VIP Secretion

The efficacy of electroacupuncture (EA) for treating patients with diarrhea-predominant IBS has been confirmed in the authors’ former research, but the regulatory mechanism of EA in IBS is still unknown. The aim of this study was to explore the relationship between the effect of EA on treating IBS rats and the activation and proliferation of mast cell (MC), the secretion of substance P(SP), and vasoactive intestinal polypeptide (VIP). The IBS rat model was set up with stress of binding limbs and colorectal distention. All rats were randomly assigned to four groups (Normal, Model, Tegaserod and EA). Hematoxylin and eosin staining has been used to observe the pathological change in the rats’ colonic mucosa and an AWR scoring system has been applied to evaluate improvement of visceral hypersensitivity in various methods of the different groups. Toluidine blue improved method (TBI) and immunohistochemistry have also been involved in observations of mucous mast cells in the colon, change of c-fos positive cells, and secretion of SP, SPR, VIP, VIPR in the local colon. Firstly, the threshold of visceral sensitivity in the rats model with IBS was remarkably reduced (P < 0.01). The MC count in colonic mucosa and c-fos positive cells count increased significantly (P < 0.01) with positive correlation within each. Secondly, EA on ST-25 and Tegaserod pouring into the stomach can inhibit the proliferation and activation of MC in the colon and regulate secretion of SP, SPR, VIP, VIPR (P < 0.01, P < 0.05), while the effect of EA is obviously superior to Tegaserod. We concluded, firstly, that the abnormal proliferation and activation of mucous mast cells in the colon, and oversecretion of neuropeptides such as SP, VIP and their receptors could be one of key mechanisms of etiology of IBS. Secondly, the inhibition of activation and proliferation and the secretion of SP, VIP could be major effects of EA when treating rats with IBS.     

Effect of gut-associated lymphoid tissue on cellular proliferation in proximal and distal colon of the rat

In previous studies, chemically induced colonic carcinomas were found to originate preferentially from crypts adjacent to lymphoid tissue. Proliferative parameters and mucosecretion were analyzed in proximal and distal rat colon in relation to the proximity of lymphoid patches. Animals received an intraperitoneal pulse of bromodeoxyuridine 1-hr before death. In both proximal and distal colon, crypts located at the immediate proximity of the lymphoid formations contained fewer mucous cells (P<0.001), but a higher percentage of proliferative epithelial cells (P<0.001) than the crypts far from lymphoid formations. The labeling index was higher in crypts adjacent to lymphoid patches compared to crypts distant from lymphoid patches only in the lower third of the crypts. The association of an increased proliferative activity and a decrease in differentiated mucosecreting cells in colonic crypts adjacent to lymphoid patches could be related to the particular sensitivity of these crypts cells to the effects of mutagens and carcinogens.     

An association between obesity and the prevalence of colonic adenoma according to age and gender

Background Epidemiologic data on obesity as a risk factor for colonic adenoma with respect to gender have not yet been confirmed. Here, we aimed to compare the prevalence of colonic adenoma and of advanced polyps in age-stratified men and women at baseline, to examine the role of body mass index (BMI) on colonic adenoma risk according to age and gender, and to examine the influence of menopausal status. Methods A total of 1744 asymptomatic patients (946 men, 798 women) who underwent colonoscopy for cancer screening at Ewha Mokdong Hospital, Seoul, Korea, between February and June 2005, were eligible. BMI was assessed, and histology, size, and location of the adenoma were examined for each patient. Women were interviewed for menopausal status and a history of hormone replacement therapy. Results A significant increase in the prevalence of colonic adenoma and of advanced polyps was found to occur with age (P for trend < 0.01). The prevalences of adenoma and advanced polyps were higher in men in most age groups (P < 0.01), but no significant difference in prevalences was observed between genderes in patients 70 years of age or older. Moreover, a positive association between BMI and the prevalence of colonic adenoma and advanced polyps was shown in relatively young individuals of both gender (men in their thirties, P < 0.05; women in their forties, P < 0.05), and premenopausal women according to hormonal status (P = 0.01). Conclusions Our data suggest that obesity increases the risk of colonic adenoma in relatively young people and in premenopausal women subject to estrogen effects.     

Growth hormone treatment increases transmural colonic growth in GH-deficient dwarf rats.

Growth hormone (GH) has been implicated as an important factor in the growth regulation of several visceral organs including the gastrointestinal tract. Our aim was to study the effects of GH administration on colonic growth in dwarf rats with an isolated GH deficiency. Dwarf rats were treated with recombinant human growth hormone (rhGH; 2.0 mg/kg/day) for four weeks and compared with saline treated dwarf rats and rats with normal pituitary function. The colonic wall composition was measured by means of stereological techniques. RhGH treatment of the dwarf rats increased body weight by 80% and proximal and distal colon weight by 63% and 90%, when compared with placebo treated dwarf rats (P< 0.01). The weight of the proximal colonic mucosa increased by 83% (P< 0.01), submucosa by 78% (P< 0.05), and the muscularis propria by 51% (P< 0.001) in rhGH treated dwarf rats compared with dwarf controls. The weight of the distal colonic mucosa increased by 88% (P< 0.01), submucosa by 88% (P< 0.05) and the muscularis propria by 58% (P< 0.05) compared with dwarf controls. The growth of mucosa involved all mucosal layers, with a 73 and 92% increase in the proximal and distal colon luminal surface area respectively (P< 0.001, P< 0.01). The food consumption, expressed as g/day/100 g BW was 13% higher in dwarf rats receiving rhGH than in placebo treated rats (P< 0.05) and normal control rats (P< 0.05). When weights of the GI tract compartments are corrected for the increase in body weight the effects of GH treatment were small or non-significant. RhGH administration in GH deficient dwarf rats induces visceral growth with a pronounced increase in colonic luminal surface area and growth of all layers of the colonic wall. These findings confirm the important role of GH in the regulation of intestinal growth.     

Detection rate and proximal shift tendency of adenomas and serrated polyps: a retrospective study of 62,560 colonoscopies

Purpose

The purpose of this study is to estimate the detection rates of adenomas and serrated polyps and to identify proximalization and associate risk factors in patients from Southern China.

Methods

Consecutive patients undergoing colonoscopy from 2004 to 2013 in Guangzhou were included. The proportions of proximal adenomas to advanced adenomas and serrated polyps were compared and potential predictors were evaluated.

Results

Colonoscopies (n?=?62,560) were performed, and 11,427 patients were diagnosed with polyps. Detection rates for adenomas, hyperplastic polyps, and serrated adenomas were 12.0, 2.5, and 0.2 patients per 100 colonoscopies. When comparing the 1st (2004–2008) to the 2nd period (2009–2013), adenoma and serrated polyp detection in proximal and distal colon both increased significantly (proximal colon [adenoma 3.9 vs. 6.1 patients/100 colonoscopies, P?<?0.001; serrated polyp 0.4 vs. 1.1 patients/100 colonoscopies, P?<?0.001]; distal colon [adenoma 6.6 vs. 7.2 patients/100 colonoscopies, P?=?0.003; serrated polyp 1.2 vs. 2.4 patients/100 colonoscopies, P?<?0.001]). Advanced adenoma detection increased over these two periods only in proximal colon (1st vs. 2nd period: 1.5 vs. 2.4 patients/100 colonoscopies, P?<?0.001), not the distal colon (P?=?0.114). Multivariate analyses showed that diagnostic period was an independent predictor for adenoma proximalization (OR?=?1.36, 95% CI 1.25–1.48, P?<?0.001), but not for advanced adenomas (P?=?0.117) or serrated polyps (P?=?0.928).

Conclusions

Adenomas and serrated polyps were increasingly detected throughout the colon, whereas advanced adenomas were only in proximal colon. A proximal shift tendency detected by colonoscopy was observed for adenomas, but not advanced adenomas or serrated polyps, in Southern China. The screening for proximal polyps should be emphasized and colonoscopy might be a preferred initial screening tool.

     

Grape Seed Extract Reduces the Severity of Selected Disease Markers in the Proximal Colon of Dextran Sulphate Sodium-Induced Colitis in Rats

Background

Grape seed extract (GSE) constitutes a rich source of procyanidins. GSE has been demonstrated to exert encouraging anti-inflammatory and anti-ulcer properties in experimental settings, although its effects on inflammation of the colon remain undefined.

Aim

To determine the effects of GSE in a rat model of dextran sulphate sodium (DSS) for ulcerative colitis.

Methods

Male Sprague–Dawley rats were gavaged daily (days 0–10) with GSE (400 mg/kg). Ulcerative colitis was induced by substituting DSS (2 % w/v) for drinking water from days 5–10. A sucrose breath test was performed on day 11 to determine small bowel function and intestinal tissues were collected for histological analyses. Statistical analysis was by one-way or repeated-measures ANOVA and p < 0.05 was considered significant.

Results

Compared to DSS-treated controls, GSE significantly decreased ileal villus height (14 %; p < 0.01) and mucosal thickness (13 %; p < 0.01) towards the values of normal controls. GSE reduced qualitative histological severity score (p < 0.05) in the proximal colon, although no significant effect was evident in the distal colon. However, GSE failed to prevent DSS-induced damage to the crypts of both colonic regions. Administration of GSE did not negatively impact metabolic parameters, nor did it induce any deleterious gastrointestinal side effects in healthy animals.

Conclusions

GSE decreased the severity of selected markers of DSS-induced colitis in the distal ileum and proximal colon, suggesting the potential as an adjuvant therapy for the treatment of ulcerative colitis. Future studies of GSE should investigate alternative delivery methods and treatment regimens, further seeking to identify the individual bioactive factors.     

Leptin reduces the development of the initial precancerous lesions induced by azoxymethane in the rat colonic mucosa

BACKGROUND & AIMS: Recent studies suggest that leptin, a hormone involved in food intake regulation, released into the circulation and gastrointestinal juice, may be a growth factor for intestine and may be involved in carcinogenesis; however, data are contradictory. This study investigates in rat colonic mucosa (1) the effects of hyperleptinemia on epithelial cell proliferation and development of aberrant crypts, earliest preneoplastic lesions, and (2) whether luminal leptin affects cell proliferation. METHODS: Leptin (1 mg/kg/d) or vehicle was administered systemically by miniosmotic pump in Fischer 344 rats either for 7 days (BrdU-labeling indices study) or 23 days (azoxymethane-induced colonic lesions study). The effects of injections or continuous infusion of leptin into the colon were also studied. RESULTS: In systemic leptin-treated rats, plasma leptin levels were 4- to 5-fold increased (P < 0.008 to P < 0.001); labeling indices were higher in proximal colon than in pair-fed control rats (P = 0.006) but unaffected in distal colon. Unexpectedly, in azoxymethane-treated rats, leptin significantly inhibited aberrant crypt foci formation in the middle and distal colon compared with controls (P = 0.006). Under these conditions, plasma insulin levels were reduced by 41%-58%, but gastrin levels were unchanged. In controls, luminal immunoreactive leptin reached the colon. A 3.6-fold increase in intraluminal leptin had no effect on epithelial cell proliferation. CONCLUSIONS: This study provides the first evidence that leptin reduces the development of chemically induced precancerous lesions in colon, perhaps through decreased insulinemia, and thus does not support an important role for leptin in carcinogenesis promotion. Moreover, the study indicates that leptin is not a potent growth factor for normal intestine.     

低蛋氨酸饮食对实验性结肠炎大鼠紧密连接蛋白表达和功能的影响

目的 研究低蛋氨酸(methionine restriction,MetR)饮食对葡聚糖硫酸钠(DSS)诱导的大鼠结肠炎的结肠黏膜病理组织学、肠黏膜通透性以及结肠上皮紧密连接蛋白表达的影响,并探讨其可能机制.方法 SD大鼠随机分为常规饮食正常组(AA组)、低蛋氨酸饮食正常组(MetR组)、常规饮食模型组(DSS+ AA组)、低蛋氨酸饮食模型组(DSS+ MetR组),每组15只.DSS建模后第21天腹主动脉采血,分析血常规、肝肾功能和电解质水平,取结肠组织行HE染色分析肠黏膜病理学变化,检测肠组织髓过氧化物酶(MPO)活性,免疫组化染色检测增殖细胞核抗原(PCNA)分析肠上皮细胞的增殖状况,采用尤斯灌流室(Ussing chamber)检测肠黏膜通透性;采用蛋白质印迹法分析肠上皮紧密连接蛋白的表达.结果 结肠炎造模大鼠出现腹泻、便血、体重下降,炎症集中在远端结肠,表现为隐窝脓肿,炎性细胞的浸润.与DSS+ AA组比较,MetR饮食干预可显著降低模型大鼠结肠的组织病理学评分[(10.55 ±3.62)分比(15.00±4.89)分,P=0.003].DSS+ MetR组和DSS+ AA组大鼠血白细胞计数、肠组织MPO活性以及PCNA免疫组化结果的差异均无统计学意义.Ussing chamber检测显示,DSS+ AA组的跨膜电阻抗显著低于AA组[(28.40±6.78)Ω·cm2比(46.53 ±4.03)Ω·cm2,P＜0.05],MetR组显著高于AA组[(60.64 ±8.40)Ω·cm2比(46.53 ±4.03)Ω·cm2,P＜0.05],DSS+ MetR组的短路电流值显著高于DSS+ AA组[(35.01 ±2.19) μA/cm2比(29.61±1.19)μA/cm2,P＜0.05].蛋白质印迹结果显示,AA组和MetR组未见claudin2蛋白表达,MetR组的结肠上皮claudin3蛋白表达量明显高于AA组;与DSS+ AA组比较,DSS+ MetR组claudin2的表达量更高,claudin3表达量更高.结论 MetR饮食对DSS诱导的结肠炎模型大鼠有明显的治疗作用,其机制可能不是通过调节炎性细胞浸润以及促进肠细胞生长的途径来缓解炎症损伤,而可能是通过改变紧密连接蛋白结构和功能而改善其肠黏膜屏障的功能,促进受损肠黏膜的修复.     

Involvement of parasympathetic pelvic efferent pathway in psychological stress-induced defecation

AIM:To investigate the role of the pelvic nerve pathway in stress-induced acceleration of colorectal transit and defecation in rats.METHODS:Surgical transection of rectal nerves(rectal branches of the pelvic nerve),vagotomy(Vag) or adrenalectomy(Adx) were performed bilaterally in rats.Number of fecal pellet output of these rats was measured during 1-h water avoidance stress(WAS).To evaluate the colonic transit,rats were given phenol red through the catheter indwelled in the proximal colon and subjected to WAS.After WAS session,entire colon and rectum were isolated and distribution of phenol red was measured.Distal colonic and rectal transit was evaluated using glass bead.Rats were inserted the glass bead into the distal colon and evacuation rate of the bead was measured.Neural activation was assessed by immunohistochemical staining of c-Fos and PGP9.5 in colonic whole-mount preparations of longitudinal muscle myenteric plexus(LMMP).RESULTS:In the sham-operated rats(sham op),WAS significantly increased defecation and accelerated colorectal transit with marked elevation of plasma corticosterone level.Compared with sham-operated rats,increase in the excretion of fecal pellets during WAS was significantly reduced by rectal nerve transection(RNT)(sham op:6.9 ± 0.8 vs RNT:4.3 ± 0.6,P < 0.05) or Vag(sham op:6.4 ± 0.8 vs Vag:3.7 ± 1.1,P < 0.05),although corticosterone level remained elevated.Adx-rats significantly increased the defecation despite the lower corticosterone level.Distribution pattern of phenol red showed RNT inhibited distal colonic and rectal transit accelerated by WAS,while Vag inhibited proximal colonic transit.Suppression of distal colonic and rectal transit by RNT was further confirmed by the bead evacuation rate(sham op:80.0% vs RNT:53.8%).WAS significantly increased the number of c-Fos-immunoreactive neural cells in the LMMP of the proximal and distal colon,whereas c-Fos expression was decreased by RNT in the distal colon(sham op:9.0 ± 2.0 vs RNT:4.4 ± 1.0,P < 0.05) and decreased by V     

Screening of stimulatory effects of dietary risk factors on mouse intestinal cell kinetics

AIM: Although epidemiological and experimental studies validate influence of genetic, environmental and dietary factors in the causation of various types of cancers including colon, results from all these sources are inconclusive. Hypothesizing that high fat diet and obesity are among the major predisposing factors in the incidence of colon cancer, we evaluated the role of diet constituted with food material derived from a tropical plant, Tamarindus indica Linn (TI). METHODS: A two part randomized double-blind study was conducted employing inbred Swiss albino mice from a single generation for the whole investigation. One day-old neonates (n=12) were subcutaneously administered with monosodium glutamate (MSG) to induce obesity (OB). At weaning these animals were maintained on modified AIN-76 diet supplemented with 10% TI and 10% fat bolus (w/w,TIFB) for 8 wk. Subsequently, in the second part of study, four groups of animals belonging to the same generation, age and gender (n=12 per group), were maintained on: AIN-76 control diet (CD); AIN-76 mixed with 10% TI extract (TI); and, mixed with 10% TI and 10% FB (TIFB) for 8 wk, to determine intestinal crypt cell proliferation, functionally-specific enzyme activities, fermentation profile, and energy preferences. RESULTS: We observed a significant increase in the crypt cell production rate in distal colonic segment of experimental animals when compared with the controls. This segment also contained significantly low butyrate levels compared to control and TIFB groups. All the experimental groups showed a gross decrease in the enzyme activities viz., succinate dehydrogenase, acid-galactosidase and dipeptidyl amino peptidase IV demonstrating pathological stress caused by the test regimens, and an altered metabolic flux in the cellular environment. CONCLUSION: We have demonstrated a cumulative response to the three dietary factors, one of which (TI) is reported, herein, for the first time to modulate kinetics of large intestinal mucosa, contributing to total risk posed by these test agents.     

Effect of Concomitant Polyethylene Glycol and Celecoxib on Colonic Aberrant Crypt Foci and Tumors in F344 Rats

We investigated whether celecoxib augments the protective effect of polyethylene glycol (PEG) on colonic aberrant crypt foci (ACF) and tumor formation in F344 rats treated with azoxymethane (AOM). Three groups of rats received AOM: I (AOM alone), II (PEG), and III (PEG/celecoxib). PEG reduced the mean number of total ACF per colon from 190 to 141 (P < 0.05; 26% reduction) and ≥4-crypt ACF from 95 to 58 (P < 0.01; 39%). Group III rats had a greater proportion of their ACF distally; whereas transverse colon ACF were reduced ∼50%, distal ACF were reduced by only ∼8% (P < 0.05). Of 13 large bowel tumors, 8 were in Group I, 4 in Group II, and 1 in Group III rats (P = 0.02). Thus in AOM-treated rats celecoxib appeared to enhance the PEG-induced reduction in colonic tumor formation, and in transverse but not distal or whole-colon ACF.     

Modified alternate-day fasting and cardioprotection: relation to adipose tissue dynamics and dietary fat intake

The relation between alternate-day fasting (ADF) and cardioprotection remains uncertain. In the present study, we examined the ability of modified ADF, with a low-fat (LF) vs high-fat (HF) background diet, to modulate adipose tissue physiology in a way that may protect against coronary heart disease. In a 4-week study, male C57BL/6 mice were randomized to 1 of 3 groups: (1) ADF-85%-LF (85% energy restriction on fast day, ad libitum fed on feed day, on an LF diet), (2) ADF-85%-HF (same protocol but HF diet), and (3) control (ad libitum fed). Throughout the study, body weight did not differ between ADF and control animals. Proportion of subcutaneous fat increased (P < .01), whereas the proportion of visceral fat decreased (P < .01), in both ADF groups. Triglyceride (TG) synthesis was augmented (P < .05) in subcutaneous fat, but remained unchanged in visceral fat. Adiponectin concentrations were elevated (P < .05), whereas leptin and resistin levels decreased (P < .05). Aortic vascular smooth muscle cell proliferation was reduced (P < .05) by 60% and 76% on the LF and HF diets, respectively. Plasma total cholesterol, TG, and free fatty acid concentrations also decreased (P < .05). In summary, modified ADF regimens alter adipose tissue physiology (ie, body fat distribution, TG metabolism, and adipokines) in a way that may protect against coronary heart disease. These beneficial effects were noted over a wide range of fat intake, suggesting that ADF may be protective even in the presence of HF diets.