Effects of Amino Acids on Inflammatory Bowel Disease and Its Signaling Pathways

The intestine is the primary organ responsible for digestion and absorption of nutrients and is frequently subjected to external environmental stimulations leading to the development of inflammatory bowel disease (IBD), which can cause serious harm to intestinal health in animals. Dietary amino acids play important roles in promoting intestinal development and maintaining intestinal health and exert diverse effects through multiple signaling pathways on the prevention and treatment of IBD, including affecting the physiological activities of intestinal epithelial cells, improving intestinal barrier function, reducing intestinal oxidative damage, regulating the production of inflammatory cytokines, and promoting the expression of endogenous antimicrobial peptides, and involved in main signaling pathways including AMP-activated kinase (AMPK), mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK), Toll-like receptors (TLRs), nucleotide binding oligomerization domain (NOD)/nuclear factor kappa-B (NF-κB). In this review, basic characteristics of IBD, effects and involved signaling pathways of the amino acids on IBD, and effects and applications of amino acids in maintaining intestinal health in livestock and poultry production were reviewed, so as to provide effective clues and strategies for dietary nutrients in the prevention and treatment of IBD.     

胃肠宁对脾虚大鼠胃肠激素和炎性细胞因子的影响

目的:探讨胃肠宁对脾虚证动物胃肠激素和炎性细胞因子的影响。方法:采用苦寒泻下法复制大鼠脾虚证模型,研究胃肠宁对脾虚大鼠血清中IL-10、IL-1β及回肠始段SP、VIP含量的影响。结果:脾虚证大鼠血清中IL-10水平显著降低(P<0.05),IL-1β水平显著升高(P<0.05),胃肠宁能在一定程度上恢复IL-10和IL-1β含量,但与自然康复组相比差异不显著(P>0.05);脾虚证大鼠回肠始段SP含量显著升高(P<0.05),VIP含量显著降低(P<0.05),胃肠宁能显著恢复脾虚大鼠回肠始段SP和VIP含量(P>0.05)。结论:胃肠宁对脾虚证具有较好的治疗作用,其作用机制主要是能显著改善脾虚大鼠回肠始段SP和VIP水平。     

电刺激疑核对TNBS诱导的IBD大鼠TGF－β表达的影响

为探讨疑核对炎症性肠病（inflammatory bowel disease,IBD）相关细胞因子TGF-β的调控作用以及在IBD的发生发展过程中发挥的作用,以三硝基苯磺酸（TNBS）诱导IBD大鼠动物模型通过Real-Time PCR和ELISA方法,利用疑核定位技术,检测急性电刺激疑核前后,细胞因子TGF-β在TNBS诱导的IBD大鼠结肠、胸腺、脾脏、外周血淋巴细胞中mRNA水平的变化和血清中蛋白浓度的变化。结果表明,急性电刺激IBD大鼠疑核后TGF-βmRNA表达水平在结肠、脾脏和外周血淋巴细胞中均显著高于对照组和假刺激组;而在胸腺中TGF-βmRNA表达降低。急性电刺激IBD大鼠疑核后血清中TGF一8蛋白浓度显著高于对照组和假刺激组。由此认为,疑核可能通过对IBD相关细胞因子TGF一8的调控,介导IBD的发生、发展过程,从而对IBD的发生、发展发挥调节作用。     

抗菌肽对蛋用仔公鸡生长性能、免疫指标及空肠组织相关细胞因子基因mRNA表达的影响

本试验旨在研究饲粮中添加不同水平天蚕素抗菌肽对海兰褐蛋用仔公鸡生长性能、免疫器官指数及空肠组织相关前炎性细胞因子基因mRNA相对表达水平的影响.选用336只1日龄健康海兰褐蛋用仔公鸡,随机分为7组,每组4个重复,每个重复12只鸡.7组试鸡分别饲喂基础饲粮(对照组),基础饲粮+150mg/kg金霉素(抗生素组),基础饲粮+150、200、250、300、350mg/kg抗菌肽(抗菌肽Ⅰ、Ⅱ、Ⅲ、Ⅳ、V组),试验期为42d.结果表明:1)抗菌肽Ⅲ、Ⅳ、V组平均日采食量显著低于对照组(P＜0.05),平均日增重各组之间差异不显著(P＞0.05),抗菌肽Ⅳ、V组料重比较对照组显著降低(P＜0.05).2)抗菌肽V组胸腺指数显著高于其他各组(P＜0.05),法氏囊指数较对照组、抗菌肽Ⅰ组显著提高(P＜0.05),抗菌肽Ⅳ、V组之间脾脏指数差异不显著(P＞0.05),与其他各试验组相比,抗菌肽V组脾脏指数显著升高(P＜0.05).3)抗菌肽V组白细胞介素-6基因mRNA相对表达水平较其他各组显著降低(P＜0.05),抗菌肽Ⅲ、Ⅳ、V组干扰素-Υ基因mRNA相对表达水平较对照组显著降低(P＜0.05),抗菌肽Ⅳ、V组肿瘤坏死因子-α基因mRNA相对表达水平较对照组显著降低(P＜0.05).综上所述,饲粮抗菌肽可不同程度提高蛋用仔公鸡生长性能、免疫器官指数,并能有效降低前炎性细胞因子基因的mRNA相对表达水平,以添加350mg/kg抗菌肽效果为最好.     

Digital hypothermia inhibits early lamellar inflammatory signalling in the oligofructose laminitis model

Reasons for performing study: The pathophysiological events inhibited by prophylactic digital hypothermia that result in reduction of the severity of acute laminitis are unknown. Objectives: To determine if digital hypothermia inhibits lamellar inflammatory signalling during development of oligofructose (OF) induced laminitis. Methods: Fourteen Standardbred horses were given 10 g/kg bwt OF by nasogastric tube with one forelimb (CRYO) continuously cooled by immersion in ice and water and one forelimb (NON‐RX) at ambient temperature. Lamellae were harvested prior to the onset of lameness (24 h post OF administration, DEV group, n = 7) or at the onset of lameness (OG1 group, n = 7). Lamellar mRNA was purified and cDNA produced for real time‐quantitative PCR analysis of mRNA concentrations of cytokines (IL‐6, IL‐1β, IL‐10), chemokines (CXCL1, CXCL6, CXCL8/IL‐8, MCP‐1, MCP‐2), cell adhesion molecules (ICAM‐1, E‐selectin), COX‐2 and 3 housekeeping genes. Data were analysed (NON‐RX vs. CRYO, NON‐RX vs. archived control [CON, n = 7] lamellar tissue) using nonparametric tests. Results: Compared with CON, the OG1 NON‐RX had increased (P<0.05) lamellar mRNA concentrations of all measured mediators except IL‐10, IL‐1β and MCP‐1/2, whereas only CXCL8 was increased (P<0.05) in DEV NON‐RX. Within the OG1 group, CRYO limbs (compared with NON‐RX) had decreased (P<0.05) mRNA concentrations of the majority of measured inflammatory mediators (no change in MCP‐1 and IL‐10). Within the DEV group, mRNA concentrations of CXCL‐1, ICAM‐1, IL‐1β, CXCL8 and MCP‐2 were decreased (P<0.05) and the anti‐inflammatory cytokine IL‐10 was increased (compared with NON‐RX limbs; P<0.05). Conclusions: Digital hypothermia effectively blocked early lamellar inflammatory events likely to play an important role in lamellar injury including the expression of chemokines, proinflammatory cytokines, COX‐2 and endothelial adhesion molecules. Potential relevance: This study demonstrates a potential mechanism by which hypothermia reduces the severity of acute laminitis, and may help identify molecular targets for future laminitis intervention.     

Evaluating a novel analgesic strategy for ring castration of ram lambs

Objective To evaluate the analgesic efficacy of the NSAIDs flunixin and meloxicam administered locally to the scrotum before ring castration. Study design Randomised, controlled, prospective study. Animals Forty eight single born male Merino lambs. Methods Lambs, aged approximately 4 weeks, were allocated to four groups for castration. Groups were: sham control; castration + saline; castration + flunixin; castration + meloxicam. Drugs (5 mL) were administered subcutaneously around the circumference of the scrotum immediately before castration. Cortisol, rectal temperature, haematology and plasma haptoglobin were measured before and up to 48 hours after treatment. Behaviour recorded by video for 12 hours after treatment was classified as pain avoidance behaviours in the first hour and postural behaviours in three 4 hour intervals. Results Ring castration (saline group) induced a bi‐phasic increase in cortisol with peaks at 90 minutes and 24 hours but no significant changes in haematology, haptoglobin or rectal temperature. Pain avoidance behaviours were increased and teat seeking decreased. Normal lying and normal standing postures were decreased and abnormal ventral lying, statue standing, abnormal standing and total abnormal postures increased. Flunixin decreased cortisol at 90 minutes (60.3 versus 117.3 nmol L^?1) and cortisol AUC (0–6 hours), decreased elevated leg movement (2.5 versus 5.4 events) and sum of pain avoidance behaviours (8.5 versus 16.7 events), improved time spent in normal ventral lying and decreased abnormal ventral lying and total abnormal postures compared to saline treated lambs. In a similar contrast, meloxicam caused non‐significant decreases in cortisol at 90 minutes, cortisol AUC (0–6 hours) and pain avoidance behaviours, and significantly improved the postural behaviours normal ventral lying (26.7 versus 15.4%) and normal standing (13.9 versus 7.5%), and reduced abnormal standing and total abnormal postures. Physiological and behavioural responses associated with ring castration for both NSAID treatment groups were generally greater than sham controls. Conclusions and clinical relevance Locally administered NSAIDs provided partial analgesia for ring castration.     

The equine alveolar macrophage: Functional and phenotypic comparisons with peritoneal macrophages

Alveolar macrophages (AMs) constitute the first line of defence in the lung of all species, playing a crucial role in the regulation of immune responses to inhaled pathogens. A detailed understanding of the function and phenotype of AMs is a necessary pre-requisite to both elucidating their role in preventing opportunistic bacterial colonisation of the lower respiratory tract and developing appropriate preventative strategies. The purpose of the study was to characterise this important innate immune cell at the tissue level by making functional and phenotypic comparisons with peritoneal macrophages (PMs). We hypothesised that the tissue of origin determines a unique phenotype of AMs, which may constitute an appropriate therapeutic target for certain equine respiratory diseases. Macrophages isolated from the lung and the peritoneal cavity of 9 horses were stimulated with various toll like receptor (TLR) ligands and the production of nitrite, tumour necrosis factor alpha (TNFα), interleukin (IL) 10 and indoleamine 2,3-dioxygenase (IDO) were measured by the Griess reaction and enzyme linked immunosorbent assay (ELISA) and/or quantitative polymerase chain reaction, respectively. Cells were also compared on the basis of phagocytic-capacity and the expression of several cell surface markers. AMs, but not PMs, demonstrated increased TNFα release following stimulation with LPS, polyinosinic polycytidylic acid (Poly IC) and heat-killed Salmonella typhinurium and increased TNFα and IDO mRNA expression when stimulated with LPS. AMs showed high expression of the specific macrophage markers cluster of differentiation (CD) 14, CD163 and TLR4, whereas PMs showed high expression of TLR4 only. AMs, but not PMs, demonstrated efficient phagocytic activity. Our results demonstrate that AMs are more active than PMs when stimulated with various pro-inflammatory ligands, thus supporting the importance of the local microenvironment in the activation status of the macrophage. This information provides a valuable knowledge base on which to improve our understanding of the role of macrophages and their microenvironment in equine innate immunity.