Objective To evaluate the effect of hepatocyte growth factor(HGF) on intestinal permeability and bacterial translocation after small bowel transplantation in rats. Methods Twenty Wistar rats were as recptors and twenty SD rats as donors. After heterotopic intestinal grafting, cyclosporine A was administered at 6mg/kg·day intramuscularly for inhibiting rejection. The SD rats were divided into 2 groups(n=10). HGF was administered at 150 μg/kg·day (HGF group) and normal saline was administered at 150 μg/kg·day (controlgroup). Intestinal permeability and bacterial translocation to the mesenteric lymph nodes and portal vein were assessed at the 8th postoperative day. Results The lactulose and lactulose/ mannitol of control group (0.0931%±0.008 5% and 0.132± 0.021) were higher than those of normal reference value (0.015 0%±0.002 0% and 0.020±0.005)（Plt;0.05）. The lactulose and lactulose/ mannitol of HGF group (0.039 6%±0.009 0% and 0.056±0.013) were also higher than those of normal reference value（Plt;0.05）.The bacterial culture positive proportion of lymphaden in HGF group and control group were 10% and 60%, showing statistically significant difference（Plt;0.05）. The bacterial culture positive proportion of portal vein in HGF group and control group were 10% and 20% respectively（P＞0.05）. Conclusion HGF can decrease intestinal permeability and bacterial translocation from the lumen of the graft to the mesenteric lymph nodes,thus improve gut barrier function, may be of help to reduce the incidence of septic complications after intestinal grafting.
The effect of parasitic ions on the results of ultraviolet A (UVA) cross-linking in iontophoresis was still not clear. In this work, the porcine sclera was cross-linked by riboflavin lactate Ringer’s solution (group A) and riboflavin normal saline (group B) in vitro, respectively. The concentration of parasitic ions in the solution was calculated. In addition, the average fluorescence intensity, penetration depth and concentration after the introduction of riboflavin and the mechanical properties of cross-linked sclera tissue were measured. The ranges of diffusion coefficient of the two solutions were also calculated, respectively. The results showed that more kinds of parasitic ions were detected in group A compared with group B, while the average fluorescence intensity, penetration depth and concentration of riboflavin and scleral elastic modulus in group B were significantly higher than those in group A when the penetration time was 10 minutes. Besides, the diffusion coefficient of riboflavin in group B was about 1.5 times larger than that in group A. The results suggested that the species of parasitic ions has a great impact on the permeability of riboflavin, and affects the mechanical properties of cross-linked sclera. The above results could provide a reference for improving the efficiency of riboflavin introduction and optimizing the formula of riboflavin in iontophoresis scleral cross-linking.
Objective To study the effect of probiotics on the change of intestinal permeability and inflammatory reaction after surgery of colorectal cancer. Methods Sixty patients who underwent colonic surgery were randomly divided into two groups: probiotic group and control group, with 30 cases in each group. Each group received nutritional support of the same nitrogen and calorie from day 3 to day 7 after operation. The patients in probiotic group were orally administrated probiotic (2 g/d) from the first day after surgery for 7 days. Every patient’s body temperature and heart rate were observed after operation, and white blood cell counts were observed before operation and on day 1, 5, 8 after operation. The levels of microbial DNA in whole blood and plasma D-lactate, and urine lactulose/mannito (L/M) ratio were measured before operation and on day 1 and day 8 after operation, respectively. In addition, the occurrence of postoperative systemic inflammatory response syndrome (SIRS) and complications of inflammation were closely observed. Results The average heart rate in postoperative 5 days was significantly lower in probiotics group than that in control group (P＜0.01). The duration of fever and the recovery time for white blood cell counts decreasing to normal were significantly less in probiotics group than those in control group (P＜0.01) as well. There was no significant difference of positive rate of microbial DNA in peripheral blood on day 1 after operation between two groups. However, the number of patients that showed positive result of microbial DNA PCR test in probiotic group （1 case, 3.3%） was significantly less than that of control group (7 cases, 23.3%）on day 8 after operation (P＜0.05). The level of plasma D-lactate in probiotic group 〔decreasing from (6.90±1.41) ng/ml on day 1 to (0.56±0.18) ng/ml on day 8〕 was also significantly lower than that in control group 〔decreasing from (6.63±1.29) ng/ml on day 1 to (0.95±0.83) ng/ml on day 8〕 on day 8 after operation (P＜0.05). Urine L/M ratio increased from 0.053±0.019 on day 1 to 0.063±0.016 on day 8 after operation in control group; while in probiotic group, the ratio decreased from 0.047±0.012 on day 1 to 0.031±0.008 on day 8 after operation, and there was significantly statistical difference of the ratio between two groups on day 8 (P＜0.01). There was no significant difference of the occurrence rate of SIRS and complications of inflammation between two groups (Pgt;0.05). Conclusion Probiotics can decrease intestinal permeability and maintain the intestinal barrier function after operation. It may be helpful for the recovery of patients with early inflammatory response after surgery of colorectal cancer.
Objective To observe the effect of glutamine （Gln） on intestinal permeability after surgery of children, also its influence on the plama level of interleukin-2（IL-2）, endotoxin and synthesize of protein through a random nutrition trial. Methods Twenty children suffered from congenital heart disease were divided into Gln group and control group with random number table, 10 cases in each group. They were all given isonitrogenous and isocaloric total paraenteral nutrition after 24 h postoperatively. In Gln group the Dipeptiven [-N （2）-L-alanyl-Lglutamine] was used with 2 ml/kg · 24h additionly. Before operation, 24h and 96 h after operation, intestinal permeability, serum level of endotoxin, IL-2, C-reaction protein, prealbumine were measured. Results Intestinal permeability increased in 24 h after cardiac surgery in two groups, while the concentration of endotoxin also increased, 96 h after surgery the intestinal permeability recovered, but the endotoxin level did not decrease in control group （P〈0. 01）. Conclusion Utilization of Gln can improve immune suppression, elevate the IL-2 level, decrease the endotoxin concentration, alleviate the infection, but has no effect on the protein synthesis after congenital cardiac operation of children.
【Abstract】ObjectiveTo investigate the influence of CO2 pneumoperitoneum on intestinal mucosa permeability in rats with liver cirrhosis. MethodsFifty rats were randomly divided into following groups: control group (n=5), cirrhosis group(n=5) and pneumoperitoneum group (n=40); the pneumoperitoneum group was further divided into 8 mm Hg group(n=20) and 13 mm Hg group (n=20). Four time points were chosen, including 0.5, 2, 6, and 12 hours after the end of pneumoperitoneum. After rat models with cirrhosis were established successfully, the abdominal cavity was insufflated with CO2 and maintained under the pressures of 8 mm Hg and 13 mm Hg respectively for two hours. The portal venous blood was collected and the levels of Dlactic acid and endotoxin were measured. ResultsThe levels of endotoxin and Dlactic acid in cirrhosis group were much higher than those of control group（P＜0.05）. The levels of serum endotoxin and Dlactic acid in pneumoperitoneum group were higher than those of cirrhosis group(Plt;0.05) regardless of pressure and time point. The endotoxin level in 13 mm Hg group was higher than that of 8 mm Hg group on different time points (F=5.466, P＜0.05), but there was no difference in Dlactic acid level between both of them（F=0.415,Pgt;0.05）.ConclusionThe intestinal mucosa permeability is increased in rats with liver cirrhosis. It can be further increased under CO2 pneumoperitoneum with certain pressure and time and in a pressuredependent manner. The permeability can decrease after removal of pneumoperitoneum.
ObjectiveThe changes of intestinal permeability and relationship of intestinal mucosa and bacterial translocation were studied in rat acute necrotizing pancreatitis (ANP) models.MethodsThe ANP models were made by injection of 5% sodium taurocholate 1.0 ml into pancreatic subcapsula.Then wistar rats were divided into four groups,control group (n=20),ANP group(n=22),treatment model group fed with lactose (n=22) and treatment model group fed with MgSO4 and antibiotic (n=22).After 72 hours,the experimental models were sacrificed.Tissues of pancreas,mesenteric lymph node, ascites were collected for microbiological study.The intestinal permeability was observed by lanthanum tracer.The blood samples were obtained from portal vein and ascites in order to assay the amount of amylase in serum.The pathologic lesions were found in the intestinal villus of the model group, including acute necrosis of intestinal mucosa,necrotichaemorrhage as well as enteroparalysis and a mass of haemorrhagic ascites.ResultsBacterial translocation of model group were markedly elevated than that of control (P＜0.05).There were statistically significant differences in bacterial translocation among three model groups （P＜0.05）.The pathologic lesions were found in the intestinal villus of the model group,including acute necrosis of intestinal mucosa,necrotichaemorrhage as well as enteroparalysis and a mass of haemorrhagic ascites.The lanthanum grain in clearance of intestinal cell of model group can be observed by eletron microscope.ConclusionThere is a severe gut barrier damage and injury in the intestinal mucosa,which lead to bacterial translocation from intestine as the source of pancreatic infection.Cleaning out enteric bacteria,improving intestinal movement and feeding with lactose could decrease bacterial translocation to treat and prevent acute necrotizing pancreatitis.
OBJECTIVE To investigate the effect of the endoexpander pressure of continuous and constant pressure expansion on the drug permeability. METHODS The expanders were divided into two groups, the normal expansion and the continuous and constant pressure expansion (4.6 kPa). Each expander was filled with 0.2% Metronidazole, then the expanders were immersed wholly in normal saline and sealed totally. At several intervals over 72 hours, the surrounding saline was sampled and the drug concentration of the sample was measured respectively. RESULTS Both groups were permeable to the Metronidazole and the concentration outside the expander would reach the effective concentration in 48 hours. The drug concentration of the continuous and constant pressure expansion was higher than that of the normal one and there was significant difference between the two groups (P lt; 0.01). CONCLUSIO The endoexpander pressure in continuous and constant pressure expansion can enhance the drug permeability. In view of this, in the course of continuous and constant pressure expansion, 0.2% Metronidazole can be used to prevent and control the infection.
Objective To observe the effect of resveratrol on retinal vasculopathy in diabetic rats. Methods Forty-five Sprague-Dawley male rats were randomly divided into the resveratrol group, treatment control group and the normal control group, 15 rats in each group. Diabetic rat models were induced with streptozotocin injection in resveratrol group and treatment control group. The same volume of sterile saline solution was injected into the rats of the normal control group. The rats of resveratrol group and treatment control group were feed with highfat diet. The rats of resveratrol group received oral gavage of resveratrol (75 mg/kg) twice a day for four months. The same volume of sterile saline solution was given by gavage in rats of treatment control group twice a day for four months. 2 ml femoral vein blood and 50 mu;l aqueous fluid of anterior chamber of the eye from rats of three groups were collected to detect fasting blood glucose, aqueous fluid glucose, cholesterol and triglyceride. The retinal vascular permeability was test by labeling with evans blue. Whole retina was isolated to detect the pericyte number. Total protein was extracted from retina to test the level of vascular endothelial growth factor (VEGF). Results The fasting blood glucose, aqueous fluid glucose, cholesterol and triglyceride in treatment control group were higher than those in normal control group, also higher than those in resveratrol group except cholesterol. The differences among the three groups were statistically significant (F=152.809, 65.230, 3.861, 15.059; P＜0.05). The retinal vascular permeability in treatment control group was higher than that in normal control group, while it in resveratrol group was lower than that in treatment control group. The differences among the three groups was statistically significant (F=11.626,P＜0.05). The pericyte number in treatment control group decreased as compared to normal control group, while it in resveratrol group increased as compared to treatment control group. The differences among the three groups was statistically significant (F=43.284, P＜0.05). The VEGF expression in treatment control group increased as compared to normal control group, while it in resveratrol group decreased as compared to treatment control group. The differences among the three groups was statistically significant (F=14.017, P＜0.05). Conclusion Resveratrol can improve abnormal retinal vasculopathy structure and function, down-regulated level of fasting blood glucose, aqueous fluid glucose, triglyceride and VEGF may be the mechanism.
ObjectiveTo investigate the effects of human placental mesenchymal stem cells (hPMSCs) transplantation on pulmonary vascular endothelial permeability and lung injury repair in mice with lipopolysaccharide (LPS)-induced acute lung injury (ALI).MethodsThe hPMSCs were isolated from the human placental tissue by enzyme digestion and passaged. The cell phenotype of the 3rd generation hPMSCs was detected by flow cytometry. Twenty-four 6-week-old healthy male C57BL/6 mice were randomly divided into 3 groups (n=8). The mice were instilled with LPS in the airway to prepare an ALI model in the ALI model group and the hPMSCs treatment group, and with saline in the control group. At 12 hours after LPS infusion, the mice were injected with 3rd generation hPMSCs via the tail vein in hPMSCs treatment group and with saline in the ALI model group and the control group. At 24 hours after injection, the lung tissues of all mice were taken. The pathological changes were observed by HE staining. The wet/dry mass ratio (W/D) of lung tissue was measured. The Evans blue leak test was used to detect the pulmonary vascular endothelial permea bility in mice. The expression of lung tissue permeability-related protein (VE-cadherin) was detected by Western blot.ResultsFlow cytometry examination showed that the isolated cells had typical MSCs phenotypic characteristics. Mice in each group survived. The alveolar structure of the ALI model group significantly collapsed, a large number of inflammatory cells infiltrated, and local alveolar hemorrhage occurred; while the alveolar structure collapse of the hPMSCs treatment group significantly improved, inflammatory cells infiltration significantly reduced, and a few red blood cells were in the interstitial lung. W/D and exudation volume of Evans blue stain were significantly higher in the ALI model group than in the control group and the hPMSCs treatment group (P<0.05), in the hPMSCs treatment group than in the control group (P<0.05). The relative protein expression of VE-cadherin was significantly lower in the ALI model group than in the control group and the hPMSCs treatment group (P<0.05), and in the hPMSCs treatment group than in the control group (P<0.05).ConclusionIntravenous injection of hPMSCs can effectively reduce the increased pulmonary vascular endothelial permeability mediated by LPS, relieve the degree of lung tissue damage, and play a therapeutic role in ALI mice.
It is a significant challenge to improve the blood-brain barrier (BBB) permeability of central nervous system (CNS) drugs in their development. Compared with traditional pharmacokinetic property tests, machine learning techniques have been proven to effectively and cost-effectively predict the BBB permeability of CNS drugs. In this study, we introduce a high-performance BBB permeability prediction model named balanced-stacking-learning based BBB permeability predictor(BSL-B3PP). Firstly, we screen out the feature set that has a strong influence on BBB permeability from the perspective of medicinal chemistry background and machine learning respectively, and summarize the BBB positive(BBB+) quantification intervals. Then, a combination of resampling algorithms and stacking learning(SL) algorithm is used for predicting the BBB permeability of CNS drugs. The BSL-B3PP model is constructed based on a large-scale BBB database (B3DB). Experimental validation shows an area under curve (AUC) of 97.8% and a Matthews correlation coefficient (MCC) of 85.5%. This model demonstrates promising BBB permeability prediction capability, particularly for drugs that cannot penetrate the BBB, which helps reduce CNS drug development costs and accelerate the CNS drug development process.