Endogenous PYY and NPY mediate tonic Y1- and Y2-mediated absorption in human and mouse colon

OBJECTIVE: To establish the functional significance of endogenous peptide YY (PYY) and neuropeptide Y (NPY) as mediators of Y(1) and Y(2) absorptive tone in colonic mucosa. METHODS: Functional studies utilized descending colon from adult mice (wild type [WT] and peptide nulls) and ex vivo human colonic tissue (from patients undergoing bowel resections) measuring changes in basal ion transport. Peak increases in ion transport to Y(1) or Y(2) antagonists (BIBO3304 300 nM; BIIE0246 1 muM) were pooled (mean +/- SEM) and compared using Student's unpaired t test (P 相似文献   

PYY3-36与饮食诱导肥胖抵抗的关系

目的研究高脂饮食诱导肥胖(DIO)及肥胖抵抗(DIOR)大鼠血浆PYY336含量及回结肠PYYmRNA的表达情况,探讨PYY336与高脂饮食诱导肥胖抵抗的关系。方法36只雌性SD大鼠,按体重随机分为高脂实验组(n=27)和基础对照组(n=9),分别给予高脂饲料和基础饲料喂养13周。据13周末体重将高脂饲料组再分为饮食诱导肥胖和饮食诱导肥胖抵抗组,比较各组大鼠能量摄入水平、血浆PYY336含量及回结肠PYYmRNA表达水平的差异。结果DIOR大鼠热能摄入量显著低于DIO大鼠(P<0.01),与对照组大鼠相比无显著性差异(P>0.05);DIOR大鼠血浆PYY336含量及回结肠PYYmRNA表达水平显著高于DIO和对照组大鼠(P<0.01);DIO与对照组相比,除回肠PYYmRNA表达水平升高外,其余指标均无显著性差异(P>0.05)。结论高脂饮食条件下,SD大鼠表现为明显的肥胖易感性差异,这种差异可能与PYY336的食欲调节密切相关,血浆PYY336含量和回结肠PYYmRNA表达水平的升高可能是导致DIOR大鼠热能摄入下降的内在机制之一。     

Dietary Fiber Intake is Associated with Increased Colonic Mucosal GPR43+ Polymorphonuclear Infiltration in Active Crohn’s Disease

G protein-coupled receptor 43/free fatty acid receptor 2 (GPR43/FFAR2) is essential for polymorphonuclear (PMN) recruitment. We investigated the expression of GPR43/FFAR2 in the colon from Crohn’s disease patients and whether dietary fiber in enteral nutrition increases GPR43+ polymorphonuclear infiltration in mucosa. Segments of ascending colon and white blood cells from peripheral blood were obtained from 46 Crohn’s disease patients and 10 colon cancer patients. The Crohn’s disease patients were grouped by the activity of disease (active or remission) and enteral nutrition with or without dietary fiber. Histological feature, expression and location of GPR43/FFAR2 and level of tumor necrosis factor-α (TNF-α), interleukine-6 (IL-6) and myeloperoxidase were assessed. The results of hematoxylin-eosin and immunohistochemistry staining revealed that the infiltration of immune cells, including GPR43+ PMN, was more severe in active Crohn’s disease patients who consumed normal food or enteral nutrition with dietary fiber than in remission patients and colon cancer patients. This finding was supported by the results of GPR43 and myeloperoxidase expression. Active Crohn’s disease (CD) patients who consumed enteral nutrition without dietary fiber exhibited severe immune cell infiltration similar to the other active CD patients, but GPR43+ PMNs were rarely observed. The level of TNF-α mRNA in active Crohn’s disease patients was higher than those of the other patients. In conclusion, the use of dietary fiber in enteral nutrition by active Crohn’s disease patients might increase GPR43+ PMNs infiltration in colon mucosa. This effect was not observed in Crohn’s disease patients in remission.     

A Review on the Role of Food-Derived Bioactive Molecules and the Microbiota–Gut–Brain Axis in Satiety Regulation

Obesity is a chronic disease resulting from an imbalance between energy intake and expenditure. The growing relevance of this metabolic disease lies in its association with other comorbidities. Obesity is a multifaceted disease where intestinal hormones such as cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), and peptide YY (PYY), produced by enteroendocrine cells (EECs), have a pivotal role as signaling systems. Receptors for these hormones have been identified in the gut and different brain regions, highlighting the interconnection between gut and brain in satiation mechanisms. The intestinal microbiota (IM), directly interacting with EECs, can be modulated by the diet by providing specific nutrients that induce environmental changes in the gut ecosystem. Therefore, macronutrients may trigger the microbiota–gut–brain axis (MGBA) through mechanisms including specific nutrient-sensing receptors in EECs, inducing the secretion of specific hormones that lead to decreased appetite or increased energy expenditure. Designing drugs/functional foods based in bioactive compounds exploiting these nutrient-sensing mechanisms may offer an alternative treatment for obesity and/or associated metabolic diseases. Organ-on-a-chip technology represents a suitable approach to model multi-organ communication that can provide a robust platform for studying the potential of these compounds as modulators of the MGBA.     

The calcium-sensing receptor affects fat accumulation via effects on antilipolytic pathways in adipose tissue of rats fed low-calcium diets

Low-calcium intake is associated with increased risk of obesity, but the mechanism underlying this is not clear. We previously reported that the calcium-sensing receptor (CaSR) plays an important role in modulating the expression of rate-limiting lipolysis enzymes in human adipocytes. In the present study, rats were fed diets containing normal [0.50% (NC)], low [0.30% (LC)], or very low [0.15% (VLC)] calcium for 15 wk. Ten rats of each group were killed at wk 5, 10, and 15 of the intervention. The LC-fed rats had greater visceral fat mass, lower serum FFA and glycerol concentrations, and greater CaSR expression in white adipose tissue than did those fed the NC diet at wk 10 and 15. Hormone-sensitive lipase (HSL) and adipose TG lipase (ATGL) protein levels were lower, whereas fatty acid synthase mRNA in white adipose tissue was greater in the LC-fed rats compared with the NC-fed rats. These differences from the NC group were greater in the VLC group than in the LC group at wk 15. In vitro experiments showed that 1,25-dihydroxycholecalciferol stimulated the expression of CaSR through the nuclear vitamin D receptor (nVDR). This resulted in an antilipolytic effect by increasing intracellular calcium, decreasing the intracellular cAMP level, and downregulating HSL and ATGL protein expression in adipocytes. These effects were suppressed by either nVDR or CaSR small-interfering RNA. These results suggest that CaSR affects fat accumulation by mediating antilipolytic pathways in adipose tissue of rats fed low-calcium diets.     

VEGF及其受体在上皮性卵巢癌组织中的表达及预后

目的 研究血管内皮生长因子（VEGF）及其受体血管内皮生长因子受体1（VEGFR1）、血管内皮生长因子受体2（VEGFR2）在上皮性卵巢癌中表达及临床预后意义。方法 采用SP免疫组化法检测139例不同卵巢组织VEGF及其受体VEGFR1、VEGFR2的表达及在上皮性卵巢癌组织中的共表达情况,并结合临床资料进行统计分析。结果 VEGF及其受体VEGFR1、VEGFR2在上皮性卵巢癌组织中的染色强度明显高于良性卵巢肿瘤及正常卵巢组织;并且VEGF及其受体在上皮性卵巢癌组织中的表达与临床分期、腹水量的差异均具有统计学意义（χ^2=4．207,P＝0．034;χ^2=7．432,P＝0．007）;在相关分析中高表达的VEGF与VEGFR2（r＝0．316,P＜0．05）、VEGFR1与VEGFR2（r＝0．415,P＜0．05）均存在相关性;VEGF及其受体三者共高表达较非共高表达患者的5年生存率差异具有统计学意义（χ^2＝4．043,P＝0．044）。结论 高表达和共表达VEGF及其受体VEGFR1和VEGFR2的患者可能存在较差预后,并且三者共表达及高表达可作为一项指导临床应用抗肿瘤血管生成药物（ Bev）靶向治疗的疗效预测分子。     

One-Year Self-Reported Appetite Is Similar in Adolescents with Obesity Who Do or Do Not Undergo Sleeve Gastrectomy

Background: With the growing prevalence of severe obesity in adolescents, sleeve gastrectomy (SG), a type of metabolic bariatric surgery (MBS), is increasingly being performed at a younger age. Data regarding changes in homeostatic and hedonic appetite following SG are conflicting in adults, with some studies showing no change and others showing a decrease in appetite. Data evaluating the effect of SG on appetite during adolescence, when appetite is more plastic, are currently lacking. Objective: To evaluate appetite changes one year after SG in adolescents with obesity vs. in non-surgical controls (NS). Methods: Thirty-nine subjects 13–21 years old with severe obesity were followed for a year; 19 underwent SG, and 20 were followed without surgery. Subjects had fasting blood tests for appetite-regulating hormones and completed a visual analog scale for appetite assessment (VAS). Results: The SG group had a decrease in body mass index (BMI) at one-year (baseline: 48.2 ± 1.7 kg/m²; one-year follow-up: 42.6 ± 1.0 kg/m² (p ≤ 0.0001)). No within- or between-group differences were noted in the one-year change in appetite in the SG and NS groups. After SG, fasting ghrelin decreased (p ≤ 0.0001); however, no changes were noted in peptide YY (PYY) levels. Changes in one homeostatic appetite measure following SG were inversely associated with changes in fasting PYY (r = −0.583, p = 0.011). Appetite changes were not associated with weight loss or final BMI. Conclusions: There were no changes in appetite measures one-year after SG from pre-surgery levels in adolescents with obesity, and appetite changes were not associated with changes in BMI. It is important to evaluate the impact of long-term appetite changes, if any, on weight loss after SG.     

Hormonal response to enteral feeding and the possible role of peptide YY in pathogenesis of enteral feeding-related diarrhoea

Diarrhoea is a common complication of enteral feeding. Previous studies have demonstrated a secretion of water and electrolytes in the ascending colon during intragastric but not intraduodenal enteral feeding. The cause of this secretion is likely to be neurohumoral in origin. This study was designed to examine the hormonal responses to enteral feeding. In vivo segmental colonic perfusion studies were undertaken. Before and at hourly intervals during these studies serum was taken for estimations of neurotensin (NT), pancreatic glucagon (PG), peptide YY (PYY) and vasoactive intestinal polypeptide (VIP). During fasting there was a median ascending colonic absorption of water in all groups. During feeding there was a net secretion in the ascending colon in both gastric groups and in the high load duodenal group, but not in the low load duodenal group. During these studies the PYY levels remained unchanged from fasting in the low and high load gastric groups. In the low and high load duodenal groups the PYY levels increased. The NT levels increased only in the high load duodenal group. There were no other changes in NT or in PG or VIP levels either between fasting and feeding, or between the gastric and duodenal groups. PYY is known to stimulate intestinal absorption. The absence of a rise during intragastric feeding may be important in the underlying mechanisms of enteral feeding-induced colonic secretion and hence enteral feeding-related diarrhoea.     

肿瘤坏死因子-α、细胞角蛋白20在结肠癌浸润中作用的研究

目的 研究TNF-α和细胞角蛋白20(CK20)在结肠癌患者组织中的表达和相关性,及与肿瘤生物学行为的关系.方法 选取手术切除并经病理检查证实为结肠癌患者30例,采用逆转录聚合酶链反应(RT-PCR)法,检测结肠癌患者癌组织、癌旁组织、切缘组织中TNF-α mRNA和CK20 mRNA的表达情况.结果 癌组织、癌旁组织、切缘组织中TNF-α mRNA阳性表达率分别为70.0%、43.3%、20.0%,三者之间比较及每两者之间比较差异均有统计学意义(P＜0.01);CK20 mRNA阳性表达率分别为63.3%、33.3%、16.7%,三者之间比较差异有统计学意义(P＜0.01),但在癌旁组织和切缘组织之间表达差异则无统计学意义(P＞0.05).TNF-α mRNA和CK20 mRNA在三种组织中的表达具有良好的相关性.TNF-α mRNA和CK20 mRNA与结肠癌分化程度无关(P＞0.05),但TNF-α mRNA与结肠癌Dukes分期、侵犯肠壁范围密切相关(P＜0.05).结论 TNF-α mRNA可以作为反映结肠癌浸润、侵袭能力的客观指标.     

Effects of Two Dietary Fibers as Part of Ready-to-Eat Cereal (RTEC) Breakfasts on Perceived Appetite and Gut Hormones in Overweight Women

The effects of an enzyme-hydrolyzed arabinoxylan from wheat (AXOS) versus an intact arabinoxylan from flax (FLAX) added to a ready-to-eat cereal (RTEC) on the postprandial appetitive, hormonal, and metabolic responses in overweight women (BMI 25.0–29.9 kg/m²) were evaluated. Subsequent meal energy intake was also assessed. Two randomized, double-blind, crossover design studies were completed. For trial 1, the participants consumed the following RTEC breakfast, matched for total weight and varied in energy content: low-fiber (LF, 4 g); high-fiber (HF, 15 g) as either AXOS or FLAX. For trial 2, the participants consumed LF, HF-AXOS, and HF-FLAX RTECs but also consumed another LF breakfast that was isocaloric (LF-iso) to that of the HF breakfasts. Perceived appetite and blood samples (trial 2 only) were assessed before and after breakfast. An ad libitum lunch was offered 4 h post-breakfast. No differences in postprandial appetite responses were observed among any breakfasts in either trial. The HF-AXOS and HF-FLAX led to increased postprandial GLP-1 and peptide YY (PYY) concentrations vs. LF-iso. No differences were observed in lunch meal energy intake among breakfast meals in either trial. Collectively, these data suggest that 15 g of low molecular weight fiber added to RTECs did not affect perceived appetite or subsequent energy intake despite differences in satiety hormone signaling in overweight females.     

Impact of inulin and oligofructose on gastrointestinal peptides

In the present paper, we summarise the data supporting the following hypothesis: dietary inulin-type fructans extracted from chicory root may modulate the production of peptides, such as incretins, by endocrine cells present in the intestinal mucosa, this phenomenon being involved in the regulation of food intake and/or systemic effects. To test this hypothesis, male Wistar rats received for 3 weeks either a standard diet or the same diet supplemented with 10 % inulin-type fructans with different degrees of polymerisation. All the effects were most pronounced with the diet containing oligofructose, and consisted of (i) a decrease in mean daily energy intake and in epididymal fat mass; (ii) a higher caecal pool of the anorexigenic glucagon-like peptide-1 (7-36) amide (GLP-1), and peptide YY (PYY), due to caecal tissue proliferation; (iii) an increase in GLP-1 and of its precursor - proglucagon mRNA - concentrations in the proximal colon; (iv) an increase in portal serum level of GLP-1 and PYY; (v) a decrease in serum orexigenic peptide ghrelin. Moreover, oligofructose supplementation improved glucose homeostasis (i.e. decreased glycaemia, increased pancreatic and serum insulin content) in diabetic rats previously treated with streptozotocin, a phenomenon that is partly linked to the reduction in food intake and that correlates with the increase in colic and portal GLP-1 content. Based on these results it appears justified to test, in human subjects, the hypothesis that dietary inulin-type fructans could play a role in the management of obesity and diabetes through their capacity to promote secretion of endogenous gastrointestinal peptides involved in appetite regulation.     

母胎界面维生素D受体表达与复发性自然流产相关及可能的机制

目的 探讨母胎界面维生素D受体(VDR)表达与复发性自然流产及胎盘激素的关系.方法 2014年7月至2014年9月在西安交通大学第一附属医院妇产科门诊收集复发性流产患者和正常早孕妇女绒毛和蜕膜组织,采用荧光实时定量聚合酶链式反应(FQ-PCR)检测两组绒毛组织和蜕膜组织中VDR及绒毛膜促性腺激素受体、雌激素受体和孕激素受体mRNA的含量,比较两组表达的差异.结果 复发性流产组绒毛组织中VDR、绒毛膜促性腺激素受体、雌激素受体mRNA相对水平低于对照组(t值分别为4.86、6.16、2.39,均P<0.05);绒毛膜促性腺激素受体和雌激素受体mRNA的表达水平与VDR表达水平明显正相关(F=10.21,P=0.01;F=14.52,P=0.00).复发性流产组蜕膜组织中VDR、绒毛膜促性腺激素受体、雌激素受体mRNA相对水平也低于对照组(t值分别为5.28、2.34、2.60,均P<0.05).结论 母胎界面VDR mRNA表达水平与早期自然流产相关,绒毛组织绒毛膜促性腺激素受体和雌激素受体mRNA的表达水平与VDR表达水平有一定的相关性.但是VDR导致自然流产的机制仍需进一步研究.     

Oral inoculation of probiotics Lactobacillus acidophilus NCFM suppresses tumour growth both in segmental orthotopic colon cancer and extra-intestinal tissue

Modulation of the cellular response by the administration of probiotic bacteria may be an effective strategy for preventing or inhibiting tumour growth. We orally pre-inoculated mice with probiotics Lactobacillus acidophilus NCFM (La) for 14 d. Subcutaneous dorsal-flank tumours and segmental orthotopic colon cancers were implanted into mice using CT-26 murine colon adenocarcinoma cells. On day 28 after tumour initiation, the lamina propria of the colon, mesenteric lymph nodes (MLN) and spleen were harvested and purified for flow cytometry and mRNA analyses. We demonstrated that La pre-inoculation reduced tumour volume growth by 50·3 %, compared with untreated mice at 28 d after tumour implants (2465·5 (SEM 1290·4) v. 4950·9 (SEM 1689·3) mm3, P<0·001). Inoculation with La reduced the severity of colonic carcinogenesis caused by CT-26 cells, such as level of colonic involvement and structural abnormality of epithelial/crypt damage. Moreover, La enhanced apoptosis of CT-26 cells both in dorsal-flank tumour and segmental orthotopic colon cancer, and the mean counts of apoptotic body were higher in mice pre-inoculated with La (P<0·05) compared with untreated mice. La pre-inoculation down-regulated the CXCR4 mRNA expressions in the colon, MLN and extra-intestinal tissue, compared with untreated mice (P<0·05). In addition, La pre-inoculation reduced the mean fluorescence index of MHC class I (H-2Dd, -Kd and -Ld) in flow cytometry analysis. Taken together, these findings suggest that probiotics La may play a role in attenuating tumour growth during CT-26 cell carcinogenesis. The down-regulated expression of CXCR4 mRNA and MHC class I, as well as increasing apoptosis in tumour tissue, indicated that La may be associated with modulating the cellular response triggered by colon carcinogenesis.     

结肠镜诊断结肠憩室30例临床体会

目的分析结肠憩室的内镜诊断情况,探讨结肠憩室病的发病情况以及临床特点。方法收集我科2011-2013年内镜下诊断的结肠憩室病30例患者资料进行分析。结果结肠憩室以右半结肠多见,其次为乙状结肠居多;来院就诊者以年龄在60岁者为多,且年龄越大,伴发憩室出血的几率越大。结论当患者出现不明原因的腹痛、便血、腹泻、便秘、急腹症时,应及时做结肠镜检查,以除外结肠憩室病变,指导临床治疗,减少误诊、漏诊的发生。     

Involvement of the Niacin Receptor GPR109a in the Local Control of Glucose Uptake in Small Intestine of Type 2 Diabetic Mice

Niacin is a popular nutritional supplement known to reduce the risk of cardiovascular diseases by enhancing high-density lipoprotein levels. Despite such health benefits, niacin impairs fasting blood glucose. In type 2 diabetes (T2DM), an increase in jejunal glucose transport has been well documented; however, this is intriguingly decreased during niacin deficient state. In this regard, the role of the niacin receptor GPR109a in T2DM jejunal glucose transport remains unknown. Therefore, the effects of diabetes and high-glucose conditions on GPR109a expression were studied using jejunal enterocytes of 10-week-old m+/db and db/db mice, as well as Caco-2 cells cultured in 5.6 or 25.2 mM glucose concentrations. Expression of the target genes and proteins were quantified using real-time polymerase chain reaction (RT-PCR) and Western blotting. Glucose uptake in Caco-2 cells and everted mouse jejunum was measured using liquid scintillation counting. 10-week T2DM increased mRNA and protein expression levels of GPR109a in jejunum by 195.0% and 75.9%, respectively, as compared with the respective m+/db control; high-glucose concentrations increased mRNA and protein expression of GPR109a in Caco-2 cells by 130.2% and 69.0%, respectively, which was also confirmed by immunohistochemistry. In conclusion, the enhanced GPR109a expression in jejunal enterocytes of T2DM mice and high-glucose treated Caco-2 cells suggests that GPR109a is involved in elevating intestinal glucose transport observed in diabetes.     

Diagnosis of the infiltrating depth of the colonic cancer by endoscopic ultrasonography (EUS)

Endoscopic ultrasonography (EUS) is the latest procedure in the field of gastroenterology and is highly evaulating now because of its unique diagnosing method. For the example, the intra- and extra-mural informations of the GI tract can be known through this technique. In this paper, we reported on the usefulness of EUS in the diagnosis of the depth invasion of the colonic cancer and introduced the new and exclusive instrument for the colon. Namely, we could obtain the accurate diagnosis in 18 out of 20 cases with the rectal or the sigmoid colon cancer. One of causes of misdiagnosis in 2 cases of early cancer was due to the ghost echo. Another cause was the cancer cells infiltration to the deeper tissue which could be recognized only by a microscope. Then, we tried to examine the entire colon in 2 cases using the new instrument and succeeded to insert the endoscope to the cecum in a short time. In conclusion, we were convinced that EUS would develop the new aspect in the diagnosis of the colonic diseases including cancer.     

Peptide YY, appetite and food intake

Obesity is taking on pandemic proportions. The laws of thermodynamics, however, remain unchanged, as energy will be stored if less energy is expended than consumed; the storage is usually in the form of adipose tissue. Several neural, humeral and psychological factors control the complex process known as appetite. Recently, a close evolutionary relationship between the gut and brain has become apparent. The gut hormones regulate important gastrointestinal functions such as motility, secretion, absorption, provide feedback to the central nervous system on availability of nutrients and may play a part in regulating food intake. Peptide YY (PYY) is a thirty-six amino acid peptide related to neuropeptide Y (NPY) and is co-secreted with glucagon-like peptide 1. Produced by the intestinal L-cells, the highest tissue concentrations of PYY are found in distal segments of the gastrointestinal tract, although it is present throughout the gut. Following food intake PYY is released into the circulation. PYY concentrations are proportional to meal energy content and peak plasma levels appear postprandially after 1 h. PYY3-36 is a major form of PYY in both the gut mucosal endocrine cells and the circulation. Peripheral administration of PYY3-36 inhibits food intake for several hours in both rodents and man. The binding of PYY3-36 to the Y2 receptor leads to an inhibition of the NPY neurones and a possible reciprocal stimulation of the pro-opiomelanocortin neurones. Thus, PYY3-36 appears to control food intake by providing a powerful feedback on the hypothalamic circuits. The effect on food intake has been demonstrated at physiological concentrations and, therefore, PYY3-36 may be important in the everyday regulation of food intake.     

粗壮女贞改善高胆碱膳食小鼠结肠屏障功能及减轻肠道炎症反应

目的 研究粗壮女贞对高胆碱膳食C57BL/6J小鼠肠道屏障功能及炎症反应的影响。方法 24只雌性C57BL / 6J小鼠随机分为正常饮食组、高胆碱膳食组和粗壮女贞干预组。干预17周后，通过苏木精-伊红染色法（HE）镜检观察结肠绒毛高度及结肠病理变化；RT - qPCR检测结肠组织中紧密连接蛋白Claudin - 1、Claudin - 2、TJP - 1、Occludin及炎症相关TNF -α、iNOS、MCP - 1的mRNA表达水平。结果 HE染色结果表明，与正常饮食组相比，高胆碱膳食组小鼠结肠绒毛高度显著降低（q = 3.129 ,P＜0.01）；与高胆碱膳食组相比，粗壮女贞干预组小鼠结肠绒毛高度升高（q = 3.149 , P＜0.01）；与正常饮食组相比，高胆碱膳食组小鼠的肠粘膜和粘膜下区域的炎症浸润增加，而粗壮女贞干预限制了其炎症的增加。RT - qPCR结果显示，与对照组相比，高胆碱膳食组小鼠结肠组织中Claudin - 1、Claudin - 2、TJP - 1 mRNA表达水平降低；与高胆碱膳食组相比粗壮女贞干预组小鼠结肠组织 Claudin - 1（q = 3.141, P＜0.01）、Claudin - 2（q = 3.329, P＜0.01）、TJP - 1（q = 3.479, P＜0.01）mRNA表达水平均升高 （P＜0.05）；与正常饮食组相比，高胆碱膳食组结肠组织中TNF -α（q = 5.305, P＜0.01）和iNOS（q = 5.242, P＜0.01）表达水平升高；与高胆碱膳食组相比粗壮女贞干预组小鼠结肠组织中 TNF -α（q = 4.015, P＜0.05）和iNOS （q = 6.005, P＜0.01）表达水平均降低。结论 粗壮女贞能够修复高胆碱膳食小鼠的肠道屏障功能损伤的同时减轻肠道炎症，这可能与结肠Claudin - 1、Claudin - 2、TJP - 1紧密连接蛋白表达上调，修复肠道屏障功能相关。