AIM： To discuss the changes of intestinal mucosal immune function in rats with experimental severe acute pancreatitis （SAP） and the regulatory effect of L-arginine. METHODS： Male adult Wistar rats were randomly di...AIM： To discuss the changes of intestinal mucosal immune function in rats with experimental severe acute pancreatitis （SAP） and the regulatory effect of L-arginine. METHODS： Male adult Wistar rats were randomly divided into pancreatitis group, sham-operation group, and L-arginine treatment group. Animals were killed at 24, 48, and 72 h after SAP models were developed and specimens were harvested. Endotoxin concentration in portal vein was determined by limulus endotoxin analysis kit. CD3＋, CD4＋, CD8＋ T lymphoo/tes in intestinal mucosal lamina propria were examined by immunohistochemistry. Secretory immunoglobulin A （SIgA） in cecum feces was examined by radioimmunoassay. RESULTS： Compared to the control group, plasma endotoxin concentration in the portal vein increased, percentage of CD3＋ and CD4＋ T lymphocyte subsets in the end of intestinal mucosal lamina propria reduced significantly, CD4＋/CD8＋ ratio decreased, and SIgA concentrations in cecum feces reduced at 24, 48, and 72 h after SAP developed. Compared to SAP group, the L-arginine treatment group had a lower level of plasma endotoxin concentration in the portal vein, a higher CD3＋ and CD4＋ T lymphocyte percentage in the end of intestinal mucosal lamina propria, an increased ratio of CD4＋/CD8＋ and a higher SIgA concentration in cecum feces. CONCLUSION： Intestinal immune suppression occurs in the early stage of SAP rats, which may be the main reason for bacterial and endotoxin translocation. L-arginine can improve the intestinal immunity and reduce bacterial and endotoxin translocation in SAP rats.展开更多
Acute pancreatitis (AP) is a common acute abdomen in clinic with a rapid onset and dangerous pathogenetic condition. AP can cause an injury of intestinal mucosa barrier, leading to translocation of bacteria or endotox...Acute pancreatitis (AP) is a common acute abdomen in clinic with a rapid onset and dangerous pathogenetic condition. AP can cause an injury of intestinal mucosa barrier, leading to translocation of bacteria or endotoxin through multiple routes, bacterial translocation (BT), gutorigin endotoxaemia, and secondary infection of pancreatic tissue, and then cause systemic in- flammatory response syndrome (SIRS) or multiple organ dysfunction syndrome (MODS), which are important factors influencing AP’s severity and mortality. Meanwhile, the injury of intestinal mucosa barrier plays a key role in AP’s process. Therefore, it is clinically important to study the relationship between the injury of intestinal mucosa barrier and AP. In addition, many factors such as microcirculation disturbance, ischemical reperfusion injury, excessive release of inflammatory mediators and apoptosis may also play important roles in the damage of intestinal mucosa barrier. In this review, we summarize studies on mechanisms of AP.展开更多
AIM： To investigate the dysfunction of the immunological barrier of the intestinal mucosa during endotoxemia and to elucidate the potential mechanism of this dysfunction. METHODS： Male Wistar rats were randomly dist...AIM： To investigate the dysfunction of the immunological barrier of the intestinal mucosa during endotoxemia and to elucidate the potential mechanism of this dysfunction. METHODS： Male Wistar rats were randomly distributed into two groups： control group and lipopolysaccharide （LPS） group. Endotoxemia was induced by a single caudal venous injection of LPS. Animals were sacrificed in batches 2, 6, 12 and 24 h after LPS infusion. The number of microfold （M）-cells, dendritic cells （DCs）, CD4＋ T cells, CD8＋ T cells, regulatory T （Tr） cells and IgA＋ B cells in the intestinal mucosa were counted after immunohistochemical staining. Apoptotic lymphocytes were counted after TUNEL staining. The levels of interleukin （IL）-4, interferon （IFN）-γ, and forkhead box P3 （Foxp3） in mucosal homogenates were measured by ELISA. The secretory IgA （sIgA） content in the total protein of one milligram of small intestinal mucus was detected using a radioimmunological assay.RESULTS： This research demonstrated that LPS-induced endotoxemia results in small intestinal mucosa injury. The number of M-cells, DCs, CD8~ T cells, and IgA~ B cells were decreased while Tr cell and apoptotic lymphocyte numbers were increased significantly. The number of CD4＋ T cells increased in the early stages and then slightly decreased by 24 h. The level of IL-4 significantly increased in the early stages and then reversed by the end of the study period. The level of IFN-T increased slightly in the early stages and then decreased markedly by the 24 h time point. Level of Foxp3 increased whereas sIgA level decreased.CONCLUSION： Mucosal immune dysfunction forms part of the intestinal barrier injury during endotoxemia. The increased number and function of Tr cells as well as lymphocyte apoptosis result in mucosal immunode- ficiency.展开更多
AIM:To test the ability of penehyclidine hydrochloride (PHC) to attenuate intestinal injury in a rat cardiopulmonary bypass (CPB) model.METHODS:Male Sprague-Dawley rats were randomly divided into six groups (eight eac...AIM:To test the ability of penehyclidine hydrochloride (PHC) to attenuate intestinal injury in a rat cardiopulmonary bypass (CPB) model.METHODS:Male Sprague-Dawley rats were randomly divided into six groups (eight each):sham-operated control;sham-operated low-dose PHC control (0.6 mg/kg);sham-operated high-dose PHC control (2.0 mg/kg);CPB vehicle control;CPB low-dose PHC (0.6 mg/kg);and CPB high-dose PHC (2.0 mg/kg).Blood samples were collected from the femoral artery 2 h after CPB for determination of plasma diamine oxidase (DAO),D-lactate and endotoxin levels.Spleen,liver,mesenteric lymph nodes and lung were removed for biochemical analyses.Intestinal tissue ultrastructure was examined by electron microscopy.RESULTS:In the sham-operated groups,high-and low-dose-PHC had no significant impact on the levels of DAO,D-lactate and endotoxin,or the incidence of intestinal bacterial translocation (BT).Serum levels of DAO,D-lactate,endotoxin and the incidence of intestinal BT were significantly increased in the surgical groups,compared with the sham-operated groups (0.543 ± 0.061,5.697 ± 0.272,14.75 ± 2.46,and 0/40 vs 1.038 ± 0.252,9.377 ± 0.769,60.37 ± 5.63,and 30/40,respectively,all P < 0.05).PHC alleviated the biochemical and histopathological changes in a dosedependent manner.Serum levels of DAO,D-lactate,and endotoxin and the incidence of intestinal BT in the high-dose PHC group were significantly lower than in the low-dose PHC group (0.637 ± 0.064,6.972 ± 0.349,29.64 ± 5.49,and 14/40 vs 0.998 ± 0.062,7.835 ± 0.330,38.56 ± 4.28,and 6/40,respectively,all P < 0.05).CONCLUSION:PHC protects the structure and function of the intestinal mucosa from injury after CPB in rats.展开更多
文摘AIM： To discuss the changes of intestinal mucosal immune function in rats with experimental severe acute pancreatitis （SAP） and the regulatory effect of L-arginine. METHODS： Male adult Wistar rats were randomly divided into pancreatitis group, sham-operation group, and L-arginine treatment group. Animals were killed at 24, 48, and 72 h after SAP models were developed and specimens were harvested. Endotoxin concentration in portal vein was determined by limulus endotoxin analysis kit. CD3＋, CD4＋, CD8＋ T lymphoo/tes in intestinal mucosal lamina propria were examined by immunohistochemistry. Secretory immunoglobulin A （SIgA） in cecum feces was examined by radioimmunoassay. RESULTS： Compared to the control group, plasma endotoxin concentration in the portal vein increased, percentage of CD3＋ and CD4＋ T lymphocyte subsets in the end of intestinal mucosal lamina propria reduced significantly, CD4＋/CD8＋ ratio decreased, and SIgA concentrations in cecum feces reduced at 24, 48, and 72 h after SAP developed. Compared to SAP group, the L-arginine treatment group had a lower level of plasma endotoxin concentration in the portal vein, a higher CD3＋ and CD4＋ T lymphocyte percentage in the end of intestinal mucosal lamina propria, an increased ratio of CD4＋/CD8＋ and a higher SIgA concentration in cecum feces. CONCLUSION： Intestinal immune suppression occurs in the early stage of SAP rats, which may be the main reason for bacterial and endotoxin translocation. L-arginine can improve the intestinal immunity and reduce bacterial and endotoxin translocation in SAP rats.
基金Project supported by the Traditional Chinese Medicine Science of Zhejiang Province (Nos. 2003C130 and 2004C142)the Medical Sci-ence and Technology of Zhejiang Province (No. 2003B134)the Technological Development of Hangzhou (No. 2003123B19), China
文摘Acute pancreatitis (AP) is a common acute abdomen in clinic with a rapid onset and dangerous pathogenetic condition. AP can cause an injury of intestinal mucosa barrier, leading to translocation of bacteria or endotoxin through multiple routes, bacterial translocation (BT), gutorigin endotoxaemia, and secondary infection of pancreatic tissue, and then cause systemic in- flammatory response syndrome (SIRS) or multiple organ dysfunction syndrome (MODS), which are important factors influencing AP’s severity and mortality. Meanwhile, the injury of intestinal mucosa barrier plays a key role in AP’s process. Therefore, it is clinically important to study the relationship between the injury of intestinal mucosa barrier and AP. In addition, many factors such as microcirculation disturbance, ischemical reperfusion injury, excessive release of inflammatory mediators and apoptosis may also play important roles in the damage of intestinal mucosa barrier. In this review, we summarize studies on mechanisms of AP.
基金Supported by Beijing Municipal Science & Technology Commission Major Scitech Program,No.H020920050130
文摘AIM： To investigate the dysfunction of the immunological barrier of the intestinal mucosa during endotoxemia and to elucidate the potential mechanism of this dysfunction. METHODS： Male Wistar rats were randomly distributed into two groups： control group and lipopolysaccharide （LPS） group. Endotoxemia was induced by a single caudal venous injection of LPS. Animals were sacrificed in batches 2, 6, 12 and 24 h after LPS infusion. The number of microfold （M）-cells, dendritic cells （DCs）, CD4＋ T cells, CD8＋ T cells, regulatory T （Tr） cells and IgA＋ B cells in the intestinal mucosa were counted after immunohistochemical staining. Apoptotic lymphocytes were counted after TUNEL staining. The levels of interleukin （IL）-4, interferon （IFN）-γ, and forkhead box P3 （Foxp3） in mucosal homogenates were measured by ELISA. The secretory IgA （sIgA） content in the total protein of one milligram of small intestinal mucus was detected using a radioimmunological assay.RESULTS： This research demonstrated that LPS-induced endotoxemia results in small intestinal mucosa injury. The number of M-cells, DCs, CD8~ T cells, and IgA~ B cells were decreased while Tr cell and apoptotic lymphocyte numbers were increased significantly. The number of CD4＋ T cells increased in the early stages and then slightly decreased by 24 h. The level of IL-4 significantly increased in the early stages and then reversed by the end of the study period. The level of IFN-T increased slightly in the early stages and then decreased markedly by the 24 h time point. Level of Foxp3 increased whereas sIgA level decreased.CONCLUSION： Mucosal immune dysfunction forms part of the intestinal barrier injury during endotoxemia. The increased number and function of Tr cells as well as lymphocyte apoptosis result in mucosal immunode- ficiency.
基金Supported by A grant from the Doctor Priming Foundation of Liaoning Province,No. 20091099
文摘AIM:To test the ability of penehyclidine hydrochloride (PHC) to attenuate intestinal injury in a rat cardiopulmonary bypass (CPB) model.METHODS:Male Sprague-Dawley rats were randomly divided into six groups (eight each):sham-operated control;sham-operated low-dose PHC control (0.6 mg/kg);sham-operated high-dose PHC control (2.0 mg/kg);CPB vehicle control;CPB low-dose PHC (0.6 mg/kg);and CPB high-dose PHC (2.0 mg/kg).Blood samples were collected from the femoral artery 2 h after CPB for determination of plasma diamine oxidase (DAO),D-lactate and endotoxin levels.Spleen,liver,mesenteric lymph nodes and lung were removed for biochemical analyses.Intestinal tissue ultrastructure was examined by electron microscopy.RESULTS:In the sham-operated groups,high-and low-dose-PHC had no significant impact on the levels of DAO,D-lactate and endotoxin,or the incidence of intestinal bacterial translocation (BT).Serum levels of DAO,D-lactate,endotoxin and the incidence of intestinal BT were significantly increased in the surgical groups,compared with the sham-operated groups (0.543 ± 0.061,5.697 ± 0.272,14.75 ± 2.46,and 0/40 vs 1.038 ± 0.252,9.377 ± 0.769,60.37 ± 5.63,and 30/40,respectively,all P < 0.05).PHC alleviated the biochemical and histopathological changes in a dosedependent manner.Serum levels of DAO,D-lactate,and endotoxin and the incidence of intestinal BT in the high-dose PHC group were significantly lower than in the low-dose PHC group (0.637 ± 0.064,6.972 ± 0.349,29.64 ± 5.49,and 14/40 vs 0.998 ± 0.062,7.835 ± 0.330,38.56 ± 4.28,and 6/40,respectively,all P < 0.05).CONCLUSION:PHC protects the structure and function of the intestinal mucosa from injury after CPB in rats.
