Research progress in gut-skin axis and its association with traditional Chinese medicine theory / 中国中药杂志

Currently, the gut-organ axis has become a hot research topic. As increasing attention has been paid to the role of gut microbiota in the health of organs, the complex and integrated dialogue mechanism between the gastrointestinal tract and the associated microbiota has been demonstrated in more and more studies. Skin as the largest organ in the human body serves as the primary barrier protecting the human body from damage. The proposal of the gut-skin axis has established a bidirectional link between the gut and the skin. The disturbance of gut microbiota can lead to the occurrence of skin diseases, the mechanism of which is complex and may involve multiple pathways in immunity, metabolism, and internal secretion. According to the theory of traditional Chinese medicine(TCM), the connection between the intestine and the skin can be established through the lung, and the interior disorders will definitely cause symptoms on the exterior. This paper reviews the research progress in the gut-skin axis and its correlation with TCM theory and provides ideas and a basis for cli-nical treatment and drug development of skin and intestinal diseases.

Protective effects of valproic acid on gut barrier function after major burn injury and its mechanism / 中华危重病急救医学

Objective To investigate the potential protective effects of valproic acid (VPA) on gut barrier function after major burn injury in rats and its mechanism.Methods Forty male Sprague-Dawley (SD) rats were divided into sham + normal saline (NS),sham + VPA,scald + NS,and scald + VPA groups,with 10 rats in each group.Rat with 55％ total body surface area (TBSA) third-degree severe-bums model was reproduced by immersing into 80 ℃ water,and the rats in sham groups were given sham-bums by immersing into 37 ℃ water.The rats after severebums were immediately treated with 0.25 mL of 300 mg/kg VPA or NS by subcutaneous injection.Rats were sacrificed at 2 hours and 6 hours after injury,and abdominal aortic blood and ileal tissue were harvested.The levels of vascular endothelial growth factor (VEGF) were determined by enzyme-linked immunosorbent assay (ELISA).The intestinal permeability was evaluated by fluorescein isothiocyanate-dextran (FITC-dextran) determination.The histomorphological changes in gut barrier were evaluated by Chiu grading system.Levels of acetylated lysine at the ninth position of histone 3 protein (Ac-H3K9),hypoxia-inducible factor 1α (HIF-1α),zona occludens 1 (ZO-1) and myosin light chain kinase (MLCK) were determined by immunofluorescence staining and Western Blot.Results Compared with sham + NS group,rats in scald + NS group showed intestinal mucosal damage 2 hours after bum injury,as well as increased mucosal permeability,protein expression levels of HIF-1 α,VEGF,MLCK,and lowered levels of AC-H3K9 and ZO-1.These changes were much more prominent at 6 hours after injury.VPA treatment significantly attenuated the bum-induced intestinal damage.Compared with scald + NS group,the protective effects in scald + VPA group was not evident at 2 hours after injury;however,intestinal damage was much less severe at 6 hours after injury (Chiu score:2.03 ± 0.27 vs.3.12 ± 0.15),intestinal permeability was significantly decreased [FITC-dextran (μg/L):709 ± 76 vs.1138 ± 75],histone acetylation was enhanced [Ac-H3K9 (gray value):1.55 ± 0.12 vs.0.48±0.12],ZO-1 degradation was significantly inhibited (gray value:0.69 ± 0.12 vs.0.43 ± 0.16),the protein expression levels of VEGF and MLCK were significantly down-regulated [VEGF (ng/mg):51.7±3.7 vs.71.2±4.3,MLCK (gray value):1.98±0.20 vs.2.80±0.24],while the HIF-1 α protein expression levels were significantly reduced at both 2 hours and 6 hours after injury (gray value:2.50±0.39 vs.3.88±0.42 at 2 hours,1.83±0.42 vs.4.42±0.41 at 6 hours,all P ＜ 0.05).Conclusions Severe bum injury can induce histone deacetylation,ZO-1 degradation and intestinal barrier dysfunction.VPA can improve the levels of histone acetylation and ZO-1,and protect intestinal epithelial barrier function.These may probably be mediated through inhibiting HIF-1α and its downstream gene VEGF and MLCK.

Interdisciplinary research of medical post-doctor / 医学研究生学报

Interdisciplinary research is one of the focus of sci-entific method discussion .In recent years a large number of interdiscipli-nary methods or engaged in interdisciplinary research and collaboration between scientists have won the Nobel prize , once again proved this point.Its profound, interdisciplinary research in the field of medicine it-self also embodies a new paradigm of modern medical science and explo-ration the cross disciplinary research applied to medical postdoctoral training work, aims to cultivate a group of clinicians is an excellent ex-perimental research and know the innovative medical amphibious expert.With the development of modern medicine and the current actual situation , the development of a single subject is far from enough .This article from the interdisciplinary talents cultivation idea or-igin, development of surgery and anatomy , informatics, imaging, such as the development of other disciplines and the close connection between the hot research in twenty-first century To expound the progress of medicine , the need for mutual cooperation between families , and by their respective areas of strengths together to carry out interdisciplinary research .

Current status on the intestinal barrier dysfunction in HIV infection / 肠外与肠内营养

Highly active antiretroviral therapy (HAART) can effectively suppress thehuman immunodeficiency virus (HIV) replication andsignificantly reduce morbidity and mortality of HIV-infectedpatients,which howevercan't completely remove the virus,and eventually progressinto chronic viral-infection disease.Chronic HIVinfection destroys host immune system,leading to intestinal barrier damage,intestinal mucosal dysfunction,microbial translocation,and further accelerates the disease progress.The reconstruction of intestinalmicroflora balance and improvement of intestinal mucosa function areessential to reestablish the host immune system.This paper will review the current research advanceson intestinal barrier damage of HIV infection and gut-target therapy of AIDS.The aim is to provide valid evidences for further research targeting improvement of treatment strategiesandreduction of morbidity and mortality in HIV infection.

Effect of high amounts of medium chain triglyceride and protein enteral nutrition on gut barrier function during the perioperative period in patient with malignant obstructive jaundice / 肠外与肠内营养

Objective:To investigate the effect of Nutrison MCT and Nutrison MF enteral nutrition on gut barrier function during the perioperative period in patient with malignant obstructive jaundice.Methods:82 cases of patients with malignant obstructive jaundice were randomized divided into Nutrison MCT group with 40 cases and Nutrison MF group with 42 cases.Enteral nutrition was given on admission.The level of urinary lactulose and mannitol(L/M) ratio,plasma endotoxin and diamine oxidase(DAO) activity on the 2nd day after admission,lday before surgery,5 days after full dose of enteral nutrition were collected.Results:Before surgery,no statistical significance difference of urinary L/M ratio,plasma endotoxin and DAO activity were found between the 2nd day after admission and 1day before surgery.After full dosing of enteral nutrition,urinary L/M ratio,plasma endotoxin and DAO activity were decreased,while Nutrison MCT group decreased more significantly than Nutrison MF group.Conclusion:Nutrison MCT can improve the gut barrier function of patients with malignant obstructive jaundice more earlier than Nutrison MF after surgery.

Glutamine and gut barrier function:underlying mechanisms and clinical application / 国际儿科学杂志

Intestinal tract is the central organ of the body's stress,and it has an important barrier function to prevent the harmful substances,such as bacteria and toxins,from the gut into the body.The main factors of intestinal barrier dysfunction are ischemia and hypoxia and endotoxin damage,and it is essential to explore the protective methods of the intestinal mucosa barrier in the early stage to prevent the organ metabolism disorder induced by intestinal derived endotoxin and bacterial translocation.Glutamine,which can effectively protect the integrity of the intestinal mucosa,maintain the normal intestinal permeability and improve the cell immunity,has been used to intensive adult patients and need further studies in the clinical application of newborns.

Visceral sensitivity, gut barrier function and autonomic nerve function in patients with diarrhea-predominant irritable bowel syndrome / 中南大学学报(医学版)

Objective:To evaluate visceral sensitivity,gut barrier function and autonomic nerve function (ANF) in patients with diarrhea-predominant irritable bowel syndrome (IBS-D),and to explore their roles in IBS-D pathophysiology.Methods:A total of 46 IBS-D patients (IBS-D group) were selected from the Department of Gastroenterology of China-Japan Friendship Hospital from October 2015 to March 2016,and 20 healthy volunteer were served as a control group (HC group).Clinical and psychological symptoms were evaluated by questionnaire,and visceral sensitivity to rectal balloon distention,gut barrier function and autonomic nerve function (ANF) were examined.The difference in the abovementioned indexes were compared between the 2 groups,and the correlations in the parameters were analyzed in the IBS-D group.Results:The scores of IBS symptom severity scale (IBS-SSS),Hamilton anxiety scale (HAMA),Hamilton depression scale (HAMD) and visceral sensitivity index (VSI) were significantly higher in the IBS-D group than those in the HC group (P＜0.01).In the visceral sensitivity test,maximum tolerable threshold in the IBS-D group was significantly decreased compared to that in the HC group (P＜0.01);there was no significant difference in first sensation threshold and defecating sensation threshold between the two groups (P＞0.05).As gut barrier function markers,the serum diamine oxidase (DAO) and d-lactate were significantly increased in the IBS-D group (P＜0.05).In ANF test,the total score and parasympathetic score as well as the proportion of abnormal scores in the IBS-D group were significantly higher than those in the HC group (P＜0.05).In IBS-D group,the HAMA,VSI and serum DAO were positively correlated with IBS-SSS (r=0.528,0.575,0.507;P＜0.01),while the 3 visceral sensitivity thresholds were negatively correlated with IBS-SSS (r=-0.636,-0.476,-0.697;P＜0.01);in addition to the IBS-SSS,the HAMA,HAMD,VSI and serum DAO were also significant negatively correlated with the visceral sensitivity thresholds (all P＜0.05);no significant correlations were found between the ANF and the other parameters.Conclusion:IBS-D patients show psychological symptoms,visceral hypersensitivity,impaired gut barrier function and abnormal ANF characterized by parasympathetic dysfunction;the former 3 factors are all associated with disease severity,and thus may play vital roles in IBS-D pathophysiology.

Correlations of enterobacteria DNA load in venous blood determined by real-time quantitative polymerase chain reaction with vital signs and blood cell count in febrile surgical patients / 中华临床营养杂志

Objective To determine enterobacteria DNA load in venous blood of febrile surgical patients using real-time quantitative polymerase chain reaction (RQ-PCR), to study the correlations between DNA load and vital signs/blood cell count, and to compare the difference between different detection methods in terms of positive rates.Methods A total of 72 blood samples were obtained for bacterial cuhure and RQ-PCR.The correlations of enterobacteria DNA load with body temperature, heart rate, while blood cell count,and percentages of leukocyte and lymphocyte were then analyzed.Results The enterobacteria positive rate determined by RQ-PCR (63.89％) was significantly higher than that by bacterial culture (9.72％) (F =4.383, P =0.036).The DNA load was significantly correlated with both body temperature and heart rate (P =0.006, r =0.323;P =0.000, r =0.411), but not with white blood cell count, percentages of leukocyte and lymphocyte, and age (P=0.438, r=0.093;P=0.825, r=0.027;P=0.451, r=-0.090;P =0.096, r =0.198).Conclusions RQ-PCR can quickly determine the enterobacteria DNA load in peripheral blood with high sensitivity.Routine blood cell count may not accurately reflect the enterobacteria DNA load in blood.Body temperature and heart rate may be influenced by various factors.

Progress in probiotics to prevent necrotizing enterocolitis in preterm infants / 国际儿科学杂志

Neonatal necrotizing enterocolitis (NEC)is a major cause of morbidity and mortality in premature infants.The most important etiology in the pathogenesis of NEC is structural and immunological intestinal immaturity.Probiotic bacteria prevent or limits disease propagation in NEC.The unique characteristics of developing intestinal epithelia focusing on gut development and colonization as well as the inflammatory propensity of immature epithelia are highlighted in this paper.Additionally, potential mechanisms of beneficial probiotic interaction with immature intestinal epithelia including immunomodulation, upregulation of cytoprotective genes, prevention and regulation of apoptosis and maintenance of barrier function are reviewed.Probiotics may restore or supply essential bacterial strains needed for gut maturation and homeostasis.Oral administration of probiotics has been suggested as a promising strategy for prevention of NEC.

Beneficial effects of ulinastatin on gut barrier function in sepsis.

Background & objectives: The gut contains some endogenous and exogenous microorganisms that can become potential pathogens of sepsis under certain circumstances. Therefore, the integrity and normal function of gut barrier is important for preventing the development of sepsis. The present study was designed to assess the effects of ulinastatin, a urinary trypsin inhibitor on gut barrier function and mortality in experimental sepsis. Methods: Male Sprague-Dawley rats were subjected to ceacal ligation and puncture (CLP) or sham procedure. Rats were then treated with ulinastatin 50,000 U/kg/day or saline. The mortality rate was determined. Histology, apoptosis assays, and PCR were performed using ileum specimens at 3, 6, and 12 h following CLP. Serum levels of tumour necrosis factor α (TNF-α) and interleukin-6 (IL-6) were also measured at 0, 3, 6, and 12 h following CLP. Results: Compared with the saline-treated CLP rats, the ulinastatin CLP rats had significantly increased survival time (P<0.05), lower histopathological scores of intestinal injury (P<0.05), reduced apoptosis detected by terminal deoxynucleotidyl transferase dUTP nick end labelling assay and caspase 3 activity (P<0.01). Moreover, RD-5 mRNA expression was significantly higher in ulinastatin-treated CLP animals than saline controls (P<0.05). These results suggested a preserved integrity and function of the gut barrier. Significantly lower plasma TNFα and IL-6 levels were detected in CLP rats with ulinastatin treatment, which contributed to increased survival time. Interpretation & conclusions: Our results suggest that ulinastatin has a therapeutic potential to prevent gut barrier dysfunction in the early stage of sepsis, thereby improving the outcome of sepsis. Further studies need to be done to understand the mechanism of action of ulinastatin.

Effects of enteral nutrition on the gut barrier function in patients with severe acute pancreatitis / 中国医师进修杂志

Objective To investigate the effects of enteral nutrition (EN) on the gut barrier function in patients with severe acute pancreatitis (SAP) and explore its clinical significance.Methods A total of 40 SAP patients from December 2009 to December 2011 was collected in this study.The 40 cases were divided into total parenteral nutrition (TPN) group (20 cases) and EN group (20 cases).The APACHE Ⅱ score and serum expression of endotoxin and intestinal fatty acid binding protein (IFABP) were compared between two groups.The serum expression of endotoxin and IFABP was determined by enzyme-linked immunosorbent assay method.Results The APACHE Ⅱ score and serum expression of endotoxin and IFABP were significantly decreased in EN group and TPN group after treatment of 1,7,14,21 d (P ＜0.05).The APACHE Ⅱ score was lower in EN group than that in TPN group after treatment of 7,14,21 d [(7.03 ±1.86) scores vs.(8.12 ±2.11) scores,(5.32 ± 1.14) scores vs.(6.87 ± 1.35) scores,(3.49 ±0.83) scores vs.(5.15 ± 1.02) scores,P ＜ 0.05].The serum expression of endotoxin was lower in EN group than that in TPN group after treatment of 7,14,21 d [(48.18 ± 15.48) EU/L vs.(60.12 ± 18.16) EU/L,(33.46 ± 12.04) EU/L vs.(51.32 ± 14.66) EU/L,(22.15 ± 7.81) EU/L vs.(35.62 ± 12.53) EU/L,P ＜ 0.05].The serum expression of IFABP was lower in EN group than that in TPN group after treatment of 7,14,21 d [(18.47 ± 3.55) ng/L vs.(22.57 ± 4.14) ng/L,(10.32 ± 2.68) ng/L vs.(18.11 ± 3.62) ng/L,(6.39 ± 2.26)ng/L vs.(12.16 ±3.06) ng/L,P ＜0.05].The APACHE Ⅱ score was positively correlated with serum expression of endotoxin (r =0.612,P ＜ 0.05) and IFABP (r =0.634,P ＜ 0.05).The serum expression of endotoxin was positively correlated with IFABP (r =0.627,P ＜ 0.05).Conclusions EN treatment shows more effective effect on improving the gut barrier function in SAP patients than TPN treatment.And it is worthy to be popularized in the clinical application.

Effects of laparoscopic radical gastrectomy on gut barrier function / 中华普通外科杂志

Objective To study the influence of laparoscopic gastric surgery on the gut barrier function (GBF).Methods There were 64 gastric cancer patients undergoing respectively laparoscopic radical procedures (32 cases) and open gastric surgery (32 cases).Blood was drawn on day one before surgery,day 1,day 3 and day 7 after the surgery for the measurement of plasma D-lacate and plasma diamine oxidase activity by using ultraviolet spectrophotometry.Results There was no statistical difference among demographic,clinicopathological characterastics between the two groups (P ＞ 0.05).The difference on the operative time,blood loss and the time starting to take food after the surgery was significant between the two groups,P ＜ 0.05.The differences of plasma D-lacate level and the diamine oxidase (DAO) on perioperatively respective all time points were not significant between the two groups,P ＞ 0.05.Conclusion Laparoscopic radical gastrectomy is comparable to open procedures in causing damage to patient's gut barrier functions.

Oxidative stress and apoptosis in gut barrier dysfunction of severe acute pancreatitis / 中华急诊医学杂志

Objective By means of animal study,investigated the gut barrier function in severe acute pancreatitis ( SAP),and role of inflammatory factors releasing,gut mucosa oxidative stress,cell apoptosis in it.Methods The animal experiment was done in the animal center of first people' s hospital,shanghai jiaotong university.Twenty four BALB/c mice were randomized ( random number) divided into two groups with twelve mice each group.The SAP group,mice received six intraperitoneal injections of cerulein at 1-hour intervals, the dose was 50μg/kg, then given one intraperitoneal injection of 10 mg/kg lipopolysaccharide ( LPS from E.Coli) for the induction of severe acute pancreatitis.The control ( sham operation) group,the mice received intraperitoneal injection of 2 ml normal saline for six times at 1-hour intervals.All the animals of each group were averaged to two batches,4 h and 8h after being operated respectively,to be anesthetized and adopted blood and tissue specimen.Then we observed the pathological change of pancreas and gut,scored it.We measured the blood value of diamine oxidase ( DAO),amylase and tumor necrosis factor-α (TNF-α).We detected content of malondialdehyde (MDA),superoxide dismutase (SOD),glutathione (GSH) and activity of xanthine oxidase (XO) in gut mucosa.We detected the casepase-3 activity and cell apopotosis by means of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) in gut mucosa,and conculated the apopotosis index (AI).Then using the PASW 18.0 software,we analyzed the data by anova and t-test,to make sure if the values were statistically different between the two groups and the mechanism of gut barrier dysfunction in panreatitis.Results At 4 h and 8 h after operation,the SAP-group-mice had significantly higher pancreas pathological score (P ＜0.01 ),blood amylase value ( P ＜ 0.05 ),gut pathological score and blood DAO and TNF-α value ( P ＜0.01 ),compared with the contral-group-mice.The gut mucosa MDA content and XO activity of mice in SAP group were significantly higher than which in control group ( P ＜ 0.01 ). The SAP-group-mice had significantly lower gut mucosa SOD content ( P ＜ 0.01 ) and GSH content ( P ＜ 0.05 ),compared with the contral-group-mice.The gut mucosa cells of mice in SAP group had significantly higher caspase-3 activity and apoptosis index than which in control group ( P ＜ 0.01 ).Conclusions In severe acute pancreatitis,inflammatory factors such as TNF-αwere waterfall-style released,induced gut mucosa suffer from ischemia-reperfusion injury,then serious oxidative stress developed in mucosa and activated caspase-3 pathway,inducing gut mucosa cells apoptose seriously,which was an important mechanism of gut barrier dysfunction.

Detection of invasive fungi DNA load in human whole blood samples with universal fungi primers and probe / 中华临床营养杂志

Objective To establish a real-time quantitative PCR(RQ-PCR)assay for fast detection of invasive fungi DNA in human whole blood samples with universal fungi primers and probe.Methods The universal fungi primers and the TaqMan-probe were designed on the basis of the multi-copy 5.8S region of the rDNA of the clinically most common invasive fungi.The invasive fungi genomic DNA were extracted with QIAamp?DNA Blood Mini Kit.A 20 μl RQ-PCR amplification system was established,and the simulated blood samples containing various given load of invasive fungi genome and the 71 whole blood samples of the surgical febrile patients were examined.Results The detection limit is 101 copies/μl amplification mixture,namely 105 copies/ml whole blood.The sensitivity and the specificity were 95.5％ and 97.6％,respectively; and the positive predictive value and negative predictive value were 98.7％ and 92.0％,respectively.The correlation coefficient of standard curve was between 0.9931 and 0.9977.The intra-and the inter-assay average coefficients of variation were(10.4 ±4.0)％ and(27.9 ± 2.0)％,respectively.The average relative recovery rate of fungi genomic DNA in blood samples was(91.0 ±7.6)％,and the average coefficients of variation of the relative recovery rate was(14.9 ±4.0)％.No fungi DNA was detected among the 71 blood samples of the surgical febrile patients.Conclusions The RQ-PCR assay for fast quantitative detection of invasive fungal DNA in human whole blood samples with the universal fungi primers and the TaqMan-probe was of high sensitivity,specificity,accuracy and precision,and is able to discriminate fungi from bacteria.The invasive fungi genome was not detected in this group of surgical patients,which may imply the less possibility of fungi translocation in the surgical febrile patients.

The effects of enteral nutrition versus total parenteral nutrition on gut barrier function in severe acute pancreatitis / 中华内科杂志

Objective To evaluate the effect of enteral nutrition (EN) versus total parenteral nutrition(TPN) on gut barrier function in patients with severe acute pancreatitis (SAP). Methods Sixtythree patients with SAP enrolled from 4 hospitals were randomly assigned into EN group(29 cases) and TPN group(34 cases). EN group patients were fed via a spiral nasojejunal feeding tube placed routinely by endoscopy or fluoroscopy, and TPN group patients were nourished intravenously with TPN during the same period. The changes of serum endotoxin, diamine oxidase, and urinary excretion of lactulose and mannitol ratio (L/M) were observed. Results Plasma concentration of endotoxin were markedly decreased in EN group as compared with that in TPN group at the 7th,14th ,21th day of entry trial [(39. 30 ± 15. 82) EU/L vs (73.05 ±21.16) EU/L,(22.64 ±14.31) EU/L vs (49.34 ±24.54) EU/L,(14.81 ± 10.93)EU/L vs ( 30. 08 ± 14. 10 ) EU/L, P ＜ 0. 05]. Plasma concentration of diamine oxidase were markedly decreased in EN group as compared with that in TPN group at the 7th, 14th day of entry trial [(9. 97 ± 3. 84)U/Lvs (19.89±9.89)U/L,(5.42±1. 84) U/Lvs (8.79 ±4.08) U/L, both P ＜ 0. 05]. The urinary L/M decreased significantly in EN group than those in TPN group at the 7th, 14th,21th day of entry trial (0.28 ±0.25 vs 0. 65 ±0.45,0.21 ±0. 18 vs 0.54 ±0.41,0.08 ±0.04 vs 0.29 ±0.06, all P＜0.05).Conclusion EN has better effect on improving intestinal barrier function than TPN in treatment of patients with SAP.

Clinical study on bacterial translocation in patients after digestive tract reconstruction / 中国现代普通外科进展

Objective:To investigate gut barrier dysfunction and bacterial translocation (BT) in patients who underwent digestive tract reconstruction and to study the relationship between BT and acute systemic inflammatory state (SIRS). Method： Sixty patients who underwent selective digestive tract reconstruction were observed. Blood were collected before surgery and 1, 3, 5 days after surgery to detect plasma diamine oxidase(DAO) and bacterial DNA. PCR analysis was performed with β-Galactosidase gene of Eschenchia coli and 16SrRNA gene as target gene. The SIRS of all the patients were observed for 10 days. Result：All the PCR results before operation were negative, while there was positive in 14 patients after digestive tract reconstruction. There were 23 patients with SIRS after surgery, and 12 patients PCR result were positive among 23 patients with SIRS. 85.7% of the patients(12/14) with positive PCR result had SIRS, while 23.9% patients (11/46) with negative PCR result had SIRS (P<0.01).The positive PCR rate in SIRS was 52.2% (12/23), which was remarkably higher than that without SIRS(5.4%, 2/37, P<0.01).The levels of plasma DAO in patients with positive PCR result was significantly higher than those of the patients with negative PCR result (P<0.01). The levels of plasma DAO in patients with SIRS was significantly higher than those of patients without SIRS (P<0.01). Conclusion:The gut barrier dysfunction was closely related to BT, and BT was closely related to postoperative SIRS. PCR analysis can be used in early diagnosis of BT, the positive PCR result might be a useful early warning sign of postoperative SIRS.

Complement and Integrative Approach in Gut Health and Immunologic Disease / 한양의대학술지

The intestine is an organ involved with absorbing, processing, and transporting food into the body. However, if one were to assess the immunological portion of the intestine and compare it with better-known immunologically functioning organs such as the spleen, the intestine would be found to be the largest such organ and the extent of its immunologic function would be found to be equally proportionate. The mucosal surface of the intestine has the ability to respond to effector cells capable of protecting the host from potentially harmful organisms or local antigens. When there is increased intestinal permeability (Leaky gut syndrome), pathogenic bacteria and its products, toxins, antigens, chemicals and incompletely digested food penetrate the intestinal epithelium and are transported throughout the body. They activate the immune system and effect the pathophysiology of acute and chronic inflammatory disease and autoimmune disease. Therefore, by a better understanding of the importance of gut barrier function and the pathophysiology of gut related immunologic disease, we can make helpful suggestions for achieving optimal intestinal health.

Protective effect of the combination of glutamine and arginine on intestinal barrier function in rats receiving fluorouracil chemotherapy / 中华临床营养杂志

@#Objective To investigate the protective effect of the combination of glutamine (Gln) and ar-ginine (Arg) on intestinal barrier function in rats receiving fluorouracil (5-FU) chemotherapy.Methods Totally 40 male SD rats receiving 5-FU chemotherapy were equally randomized into four groups:enteral nutrition group,Gln group (enteral nutrition+Gln),Arg group (enteral nutrition+Arg),and Arg+Gln group (enteral nutri-tion+Arg+Gln).Observe the changes post chemotherapy such as the changes of body weight and urine lactulose/mannitol ratio before and after chemotherapy were recorded.On the 8 th post-therapy day,the blood endotoxin level in portal vein was measured,and lymph nodes and blood in portal vein were taken for bacterial culture;colon and jejunum specimens were also taken to measure the height of jejunum villus and the thickness of colon and jejunum.Results Body weights of Gln group,Arg group,and Arg+Gln group significantly increased after chemotherapy (P<0.05).The change of body weight was significantly lower in Arg+Gln group than in Gln group (P=0.002),while no such difference was found when compared with that in Arg group (P>0.05).Lactulose/manni-tol ratio in each group significantly increased after chemotherapy (P<0.05),and the change of lactulose/mannitol ratio was significantly higher in the enteral nutrition group than those in other groups (P=0.000);however,no such difference was found among other groups (P>0.05).The blood endotoxin level in portal vein was signifi-cantly higher in enteral nutrition group than in other groups (P=0.000);the endotoxin level was significantly lower in Gln group than in Arg group (P=O.035) and Arg+Gln group (P=0.000);however,no such differ-ence was found between Arg group and Arg+Gln group (P=0.109).The height of jejunum villus and the thick-ness of jejunum were significantly lower in enteral nutrition group than those in the other groups (P=O.000);the thickness of colon was significantly lower in enteral nutrition group than those in Arg group and Arg+Gln group (P=0.000);however,no such difference was found when compared with Gln group (P=0.058).The thickness of colon (P=0.040) and jejunum (P=0.010) was significantly higher in Gln group than that in Arg group;but there was no significant difference in term of the height of jejunum villus (P=0.286).Compared with Arg+Gln group,the thickness of jejunum in Gln group was significantly higher,but there was no significant difference in terms of the height of jejunum villus (P=0.286) or the thickness of jejunum (P=0.190).The thickness of co-lon was significantly lower in Arg group than in Arg+Gln group (P=0.010),while no such significant difference was found in terms of the height of jejunum villus (P=0.803) or the thickness of colon (P=0.059) when com-pared with Arg+Gln group.The bacterial culture results were not significantly different among all groups.Conclu-sions The combination of Arg and Gln has protective effects on intestinal barrier in rats receiving 5-FU chemother-apy.The protective effect of Gln is superior to that of Arg.No synergistic effect exists between Arg and Gln.

Change of high mobility group box 1 and effect of drainage of intestine lymph fluid on rat gut barrier during intestine ischemia-reperfusion / 中华临床营养杂志

Objective To investigate the change of high mobility group box 1 ( HMGBI ) after intestine ischemia reperfusion (I/R) in rats, compare the effect of drainage of intestine lymph fluid on gut barrier, and ex- plore the possible mechanism of iachemia-reporfusion injury. Methods Thirty-two Sprague-Dawley (SD) rats (SPF grade) were randomly divided into4 groups with 8 rats in each group: blank group, sham group, intestine is-chemia-reperfusion (I/R) group, and intestine ischemia-reperfusion with drainage of intestine lymph fluid (I/R +drainage) group. Indicators of gut barrier function damage, translocation of endotoxin, and change of HMGB1 and cytokines were detected after intestine ischemia-reperfusion injury. Results The gut barrier function damage and levels of endotoxin, HMGBI, tumour necrosis factor-alpha ( TNF-α), interleukin-6 ( IL-6 ), interleukin-1 beta (IL-1β), and soluble intercellular adhesion molecule-1 (sICAM-1) were significantly lower in blank group and sham group than in I/R group and I/R + drainage group ( P < 0. 05 ). Compared with the intestine I/R + drainage group, the levels of endotoxin and cytokines were significantly higher in the intestine I/R group. The level of HMGB1 was slightly higher than that in the intestine I/R + drainage group, but such difference was not statistically significant ( P > 0. 05 ). lmmunohistochemical staining also revealed that the expression of HMGB1 was significant- ly higher in I/R group than in I/R + drainage group. Conclusions Intestine iachemia-reperfusion injury can lead to the injury of intestine mucosal barrier and increase HMGB1 level HMGB1 may deteriorate gut barrier function and increase the leveh of systemic cytokines. Drainage of lymph fluid can block the gut-lymph pathway and thus decrease the levels of endotoxin and cytokines in systemic circulation and attenuate intestine ischemia-reperfusion injury.

The effects of Nutrison on rat gut barrier after 5-FU chemotherapy / 国际外科学杂志

Objective To investigate and assess the effects of nutrison on rat gut barrier after 5-FU chemo-therapy. Methods Thirty male Sprague-Dawley rats were randomly assigned to three groups: EN group: nutrison intestinal nutrition; STD group: nutrison intestinal nutrition + chemotherapy; CHOW group: chow+ chemotherapy. The changies such as weight, lactulose / mannitol of urine samples before and after chem-otherapy were observed. At the 8th day, colon as well as jejunum tissue were also sampled for pathological examination to measure the height of jejunum villi, the thickness of colon and jejunum. Results Compared to EN group, the body weight the height of jejunum mucosa and the thickness of colon / jejunum loss of STD group was significantly decreased, as well as the L/M inceased. The data showed that CHOW group was bet-ter than EN group. Conclusions Intraperitoneal injection of 5-FU increased the intestinal permeability of rats and damaged the function of intestinal barrier. The intestinal mucosal protection effect of nutrison EN in post-chemotherapy rats was weaker than the effect of a free-eating group.