ObjectiveTo explore the mechanism of liver capillary permeability in rats with severe acute pancreatitis (SAP). MethodsTotally 40 healthy Sprague-Dawley (SD) rats were randomly divided into two groups: sham operation (SO) group and SAP group, SAP group were divided into four subgroups according to sampling time (3 h， 6 h, 12 h， and 24 h). The model was established by injecting 5% sodium taurocholate retrogradely into pancreaticobiliary ducts. The changes of tumor necrosis factor-α (TNF-α), pathohistology, and tissue moisture content were compared among different groups. Liver occludin protein expression was analyzed by immunohistochemistry method, and occludin mRNA was measured by RT-PCR. ResultsThere was no significant pathological changes of liver tissue in the SO group. Typical pathological changes of SAP， such as interstitial edema, vasodilatation, infiltration of inflammatory cells, were found in the SAP group. TNF-α level and tissue moisture content of each phase increased gradually, and the highest level appeared at 24 h within the observing period. The two above indicators at different time point in subgroups were significantly different from each other and higher than those in the SO group (Plt;0.05)． In the SAP group, the expression of occludin and it’s mRNA began to decrease at 3 h to the bottom at 6 h and rebounced significantly at 12 h, 24 h compared with those at 6 h (Plt;0.05), but still lower than those in the SO group (Plt;0.05). ConclusionUpregulation in TNF-α and subsequent downregulation in occludin protein and mRNA maybe bly related to the severe liver capillary permeability in rats with SAP.
ObjectiveTo determine the effects of different volume fluid resuscitation on intestinal injury and the permeability of intestine in hemorrhagic shock rats. MethodsSprague-Dawley male rats(n=72) were randomly equally divided into 4 groups after the model establishment of blood pressure-controlled hemorrhage, 45, 30, and 15 mL/(kg·h) of fluid resuscitation were performed in high dosage of resuscitation(HLR), moderate dosage of resuscitation(MLR), and low dosage of resuscitation(LLR) group respectively, but rats of Sham group didn't accept fluid resuscitation. After resuscitation, ten centimeters ileum was harvested for testing intestinal permeability. Then 6 rats of each group were sacrificed at 24, 48, and 72 hours after fluid resuscitation respectively. Over the specified time interval, blood was collected for testing levels of lactic acid and plasma tumor necrosis factor-α(TNF-α). The ileums of 3 resuscitation groups were obtained for testing the ratio of wet weight to dry weight and observing the histological changes. ResultsAfter resuscitation, the intestinal permeability was higher in HLR group(P<0.05). At 3-8 hours after resuscitation, rats of Sham group were all died, and the other rats of 3 groups were all alive. The level of plasma lactic acid was lower in LLR group than those of other 2 groups at 24 hours(P<0.05). The levels of TNF-α were higher in HLR group than those of other 2 groups at 24, 48, and 72 hours(P<0.05), and at 48 hours, level of TNF-α in LLR group was lower than MLR group(P<0.05). At 24 hours after resuscitation, ratio of intestinal wet weight to dry weight in LLR group was the lowest, and HLR group was the highest(P<0.05). According to the histopathology, intestinal injuries of the 3 groups were tend to be remission with the time, and at 48 and 72 hours after resuscitation, intestinal villus of LLR group appeared to be normal. ConclusionLimited fluid resuscitation of 15 mL/(kg·h) could not only decrease the levels of lactic acid and TNF-α, but also moderate the intestinal permeability and the intestinal injury in early stage after shock and surgery.
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.
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.
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.
【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.
In order to establish a bone scaffold with good biological properties, two kinds of new gradient triply periodic minimal surfaces (TPMS) scaffolds, i.e., two-way linear gradient G scaffolds (L-G) and D, G fusion scaffold (N-G) were designed based on the gyroid (G) and diamond (D)-type TPMS in this study. The structural mechanical parameters of the two kinds of scaffolds were obtained through the compressive simulation. The flow property parameters were also obtained through the computational fluid dynamics (CFD) simulation in this study, and the permeability of the two kinds of scaffolds were calculated by Darcy's law. The tissue differentiation areas of the two kinds of scaffolds were calculated based on the tissue differentiation theory. The results show that L-G scaffold has a better mechanical property than the N-G scaffold. However, N-G scaffold is better than the L-G scaffold in biological properties such as permeability and cartilage differentiation areas. The modeling processes of L-G and N-G scaffolds provide a new insight for the design of bone scaffold. The simulation in this study can also give reference for the prediction of osseointegration after the implantation of scaffold in the human body.
ObjectiveTo investigate the clinical effect and mechanism of Chinese heat-clearing and phlegm-resolving recipe in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). MethodsA randomized controlled trial (RCT) was conducted. A total of sixty in-patients with AECOPD of phlegm heat and phlegm turbidity in lungs were randomly allocated to treatment group and control group with an equal number of patients between October 2009 and March 2010. The treatment duration was 10 days. Symptom scores of traditional Chinese medicine (TCM), pulmonary function, white blood cell count, polymorphonuclear neutrophils, C-reactive protein and the plasma concentration of bactericidal/permeability increasing protein (BPI) and interleukin (IL)-8 and IL-10 were detected. ResultsFor TCM syndrome of phlegm heat and phlegm turbidity, there was a statistical difference between the two groups after treatment (P<0.05). Cough, sputum amount, expectoration and coated tongue were improved obviously in the treatment group (P<0.05). The total explicit efficiency rate and effective rate were 56.0% and 84.0% in the control group and 82.1% and 92.9% in the treatment group respectively. The total explicit efficiency rate was significantly different between the two groups (P<0.05), while the total effective rate was not significantly different (P>0.05). Plasma concentration of IL-8 decreased markedly in the treatment group and IL-10 and BPI increased obviously. There was no significant difference in the change of BPI, IL-8 between the two groups (P>0.05), except for IL-10 (P<0.05). ConclusionChinese heat-clearing and phlegm-resolving recipe can improve signs and symptoms of TCM in the treatment of AECOPD (phlegm heat and phlegm turbidity in lungs), by the potential mechanism of increasing the level of IL-10.
Existing neuroregulatory techniques can achieve precise stimulation of the whole brain or cortex, but high-focus deep brain stimulation has been a technical bottleneck in this field. In this paper, based on the theory of negative permeability emerged in recent years, a simulation model of magnetic replicator is established to study the distribution of the induced electric field in the deep brain and explore the possibility of deep focusing, which is compared with the traditional magnetic stimulation method. Simulation results show that a single magnetic replicator realized remote magnetic source. Under the condition of the same position and compared with the traditional method of stimulating, the former generated smaller induced electric field which sharply reduced with distance. By superposition of the magnetic field replicator, the induced electric field intensity could be increased and the focus could be improved, reducing the number of peripheral wires while guaranteeing good focus. The magnetic replicator model established in this paper provides a new idea for precise deep brain stimulation, which can be combined with neuroregulatory techniques in the future to lay a foundation for clinical application.
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.