PURPOSE: To investigate the influence of transforming growth factor-beta (TGF-beta;) on endotoxin-induced uveitis (EIU). METHODS: TGF- beta; was abstracted from humam platelets using Bio-gel P-60 chromatography. It was introduced either topically(drops) or intraperitoneally into the SD rats after footpad injection of lipopolysaccbaride(LPS). The inflammation in the anterior uvea was clinically evaluated with slitlamp every day. RESULTS :TGF-beta; obtained from Biogel P-60 chromatography displayed single band on SDS-PAGE,showing a molecular weight of 12 500 EIU occurs significantly earlier and more severe in the rats which only received LPS injection than in the TGF-beta; treated rats. The duration of the inflammation was also much longer in the untreated rats than in the treated rats (P＜0. 001). CONCLUSION: TGF-beta; purified from human platelets may partly prevent the development of EIU and effectively reduce the severity of the inflammation induced by LPS injection. （Chin J Ocul Fundus Dis,1996,12: 101-104)
Objective The effects of endotoxin, cytokines, nitric oxide were reviewed in the development of hyperdynamic circulatory syndrome in portal hypertension. Methods Liceratures of overseas main studies in hyperdynamic circulatory syndrome of portal hypertension in recent 10 years were reviewed. Results The hyperdynamic circulatory syndrome was found in 30%-50% of patients with cirrhosis and in all animal models of portal hypertension. The research results of the effects of endotoxin, cytokines, nitric oxide in the development of hyperdynamic circulatory syndrome were different. Conclusion Hyperdynamic circulatory syndrome contribute to the maintenance and aggregation of portal hypertension. Endotoxin, cytokines, nitric oxide may play a role in the development of hyperdynamic circulatory syndrome. Nitric oxide is a more important factor. The effect of other factors is probably mediated by nitric oxide.
Objective To observe the expression of matrix metalloproteinase-9 (MMP-9), its tissue inhibitor of matrix metalloproteinase (TIMP-1), inducible nitric oxide synthase (iNOS) and contents of nitric oxide (NO) in the ocular tissues of Sprague-Dawley (SD) rats with endotoxin induced uveitis（EIU）. Methods Ninety SD rats were randomly divided into experimental (81 rats) and control group (9 rats). The model of EIU was induced in rats in experimental group by injecting with lipoplysaccharide (LPS) 200 μl into the hind feet pads, while the rats in the control group were not injected. Nine rats were executed 0, 6, 12, 18, 24, 48, 72, 96 hours and 7 days, respectively, after injecting with LPS; the NO content and concentration of protein in the aqueous humor in blood plasma, aqueous humor, and uveal tissues were detected. The expressions of MMP-9, TIMP-1 and iNOS in the ocular tissues were detected by immunohistochemistry, and the average absorbance (A) value was evaluated by computer medical image analysis system. Results iNOS, MMP-9 and TIMP-1 expressed in the epithelial cells of iris and ciliary body and exudated inflammatory cells of rats. The concentration of protein in the aqueous humor, the contents of NO in blood plasma, aqueous humor, and uveal tissues, and A value of MMP-9 had obvious relativity with the inflammatory extent, while no positive correlation was found between the inflammatory extent and the A value of iNOS and TIMP-1. Expression of iNOS was found 6 hours after injection, reached the peak after 12 hours, and then dropped gradually. The expression of TIMP-1 could be seen 24 hours after injection, and reached its peak after 72 hours. Conclusion The content of NO and expressions of iNOS, MMP-9 and TIMP-1 changes from the beginning and during the development of EIU, which suggests that NO, iNOS, MMP-9 and TIMP-1 are involved in the pathologic process of EIU. (Chin J Ocul Fundus Dis, 2005, 21: 371-374)
PURPOSE:To investigate and changes of the retina and the chorid induced by lipopolysaccharide (LPS)in Lewis rats and to compare the results obtained on tissue wholemounts and sections. METHODS:Immunohistochemistry was carried out both on wholemounts of the retina and the chorid-sclera complex and on ocular sections from normal Lewis rats and those after LPS injection. RESULTS:It was shown on the tissue wholemounts that monocytes were attached to retinal blood vessels and emigrated into the choroid as early as 4hrs after LPS injection. Severe involvement of the retina and macrophages into whole area of these tissues.Furthermore increasing number of major histocompatibility complex classⅡ(MHC classⅡ)positive cells was observed in the choroid.The results on tissue sections revealed that the retina and the choroid were both involved as videnced by infiltration of these cells at some time points after LPS injection. CONCLUSION:Wholemount technique provides undoubtful evidences to show that the retina and choroid are primarily and severely involuted after LPS injection.The endotoxin induced uveitis is,for the first time,presumed to be model for human generalized uveitis. （Chin J Ocul Fundus Dis,1996,12:33-36）
Objective To summarize the recent progress in pathogenetic, diagnostic and therapeutic researches on the intestinal barrier dysfunction (IBD) of severe acute pancreatitis (SAP). MethodsThe advancement of IBD in SAP, which was published recently at home and abroad, was collected and reviewed. Results The pathogenesis of IBD in patients with SAP was complex. Ischemia-reperfusion injury, endotoxin, inflammatory mediators and gastrointestinal hormone played an important role in the process of IBD. There were many ways to detect IBD, and the ratio of lactulose and mannitol, plasma diamine oxidase were relatively ideal markers. Medical therapies, such as treatment of SAP and maintaining the perfusion of intestines, were essential to cure IBD. On this basis, the propulsives, nutritional support and traditional Chinese drugs should be administered reasonably. Conclusions IBD is a sophisticated process of pathophysiology. In recent years, abundant of animal experiments and clinical researches have provided new clue for prevention and cure of IBD, but further researches are still needed on the mechanism of the cells and molecules implicated.
To study the role of endotoxin in acute hemorrhagic necrotizing pancreatitis (AHNP), the change of endotoxin were studied in rats AHNP models by injection of 5% sodium taurocholate 1 ml/kg into pancreatic duct, and the effects of recombinant interleukin-2 (IL-2) in the treatment of AHNP were observed in this experiment. The results indicated that endotoxin involved the aggravation of AHNP and was associated with the increase of serum phospholipas-2 (PLA2), and these mediators were positively correlated with severe degrees of pancreatic damage. The results also suggeste that IL-2 might inhibit the overexpression of endotoxin and PLA2 and mitigate the pancreatic injury and decrease the 72h-mortality rate of AHNP from 66.7% to 26.7% (Ｐ＜0.01). Endotoxin might play a major role in the pathogenesis of AHNP and IL-2 might have a potential role in the treatment of AHNP.
Objective To observe barrier function changes of gut mucosa in rats with acute respiratory distress syndrome(ARDS)．Methods Forty SD rats were randomized to an experiment group (n：30)and a control group(n=10)．Oleic acid was injected via vena femoralis to establish ARDS ratmode1．Subgroups in the experiment group were randomly divided by time 30 min，2 h，4 h interval after injection(n=10 in each subgroup)．Concentration of D-lactate and endotoxin and activity of diamineoxidase in blood plasma were measured．Histopathological changes of small intestine were observed under light microscope．Results Compared with the control group，the activation of diamine oxidase in the experiment group was higher after 30 min of injection(Plt;0.01)．Concentration of D-lactate，the activity ofdiamine oxidase and endotoxin level in the experiment group were all elevated after 2 hours of injection(all Plt;0.05)，and further elevated after 4 hours．In the rats’villous interstitial after 2 hours of the injection，there were edema，hyperemia，and infiltration of neutrophils，eosinophils and lymphocytes．After 4 hours ofthe injection，the villous epithelium showed desquamation，necrosis，denaturalization and erosion，associated with infihration of lymphocytes and neutrophils in the mucosa．Conclusion In oleic acid-induced ARDS．permeability of gut mueosa increases and gut barrier is dysfunctional．
【Abstract】Objective To investigate the preventive role of selective decontamination of the digestive tract (SDD) in gut-originated endotoxemia in acute necrotizing pancreatitis (ANP). Methods A lethal model of ANP was reproduced in Wistar rats by retrograde infusion of artificial bile into the main pancreatic duct. Normal control group (n=6), sham operation group (n=6), ANP group (n=14) and ANP+SDD (polymycin E, tobramycin and nystatin mixture) group (n=8) were randomly devided. Visceral pathologic changes, serum levels of TNFα and IL-1β, intestinal bacterial flora, plasma D(-)lactate and endotoxin contents, as well as the mortality were examined at 72h after operation in each group. Results Necrosis and inflammation of pancreas, with a remarkable elevation of serum TNFα and IL-1β and intestinal flora disturbance (with E.Coli content risen significantly) were seen in ANP rats. Simultaneously, ANP rats displayed elevated plasma concentration of D(-)lactate and endotoxin. In SDD group, enterobacteraceae and yeast were markedly depressed, while anaerobes were well preserved, with the value of B/E 〔Bifidobacterium/E.Coli, log10(CFU/CFU）〕 elevated in the ileac mucous membrane (1.73±1.23 vs -0.37±0.72 in ANP group,P＜0.01) and in the caecum content (∞ vs 0.88±0.77). In addition, depressed levels of D(-)lactate 〔（3.95±1.83） mg/L vs （8.05±3.05） mg/L in ANP group,P＜0.01〕, endotoxin 〔（0.227±0.084） EU/ml vs （0.423±0.155） EU/ml in ANP group, P＜0.01〕 and TNFα 〔（15.41±10.32） ng/L vs （46.79±24.31） ng/L in ANP group P＜0.01〕 in systemic or portal vein were observed in the SDD group. Moreover, SDD group displayed a declined 72h mortality(14.3% vs 58.8% in ANP group, P=0.005). Conclusion ANP is associated with gut barrier disorder and gut flora imbalance, which may exacerbate the process of gut-originated endotoxin translocation. By protecting gut flora and gut barrier against disorder, SDD attenuates ANPrelated endotoxemia and improves the outcome. SDD is advisable for the prophylaxis of gut-originated endotoxemia complicated from ANP.
Objective To investigate the effect of recombinant human growth hormone (rhGH) on intestinal bacteria and endotoxin translocation in experimental obstructive jaundice. MethodsObstructive jaundice rat models were made and divided into three groups: sham operation (SO) group, obstructive jaundice (OJ) group and obstructive with rhGH (OG) group. The number in each group was 20. The mice in rhGH group underwent subcutaneous injection each day of Saizen, with the dose of 0.75 u/kg, while SO group and OJ group received nitric sodium injection. All these maitained for 2 weeks, then the animals were killed and the endotoxin were determined by limulus test, and bacterial cultures of ascites, blood, mesenchymal lymph node, kidney, spleen and liver were made, and the height of villi and the thickness of intestinal walls were examined.ResultsThe value of endotoxin in OJ group was (0.77±0.03) u/ml, higher than that in OG group and SO group, while it was (0.40±0.02) u/ml and (0.33±0.03) u/ml (Plt;0.01). The bacteria translocation rate in OJ group was 58.8%, much higher than that in OG group, which was 10.0% (Plt;0.01). There was no difference between OG group and SO group (Pgt;0.05). Villi height in OJ group was (183.39±11.09) μm, and thickness was (255.62±16.58) μm. While in OG group was (237.52±13.65) μm, and (320.81±14.34) μm (Plt;0.01) respectively.Conclusion rhGH has significant effect on protecting the injuried mucosa barrier in obstructive jaundice, and can decrease endotoxemia and bacteria translocation.
TO investigate the relationship between endotoxemia and structural change in the pancreatic tissue and therapeutic effects of naltrexone (NTX) on experimental acute hemorrhagic necrotizing pancreatitis in rats. The model of acute hemorrhagic necrotizing pancreatitis (AHNP) of rats was induced by retrograde injection of 5% sodium taurocholate into the pancreatic duct. One hundred and ten Wistar rats were randomly divided into three groups: control group (n=20),AHNP group (n=45) and NTX treatment (n=45) group. The weight of pancreas and plasma levels of amylase and endotoxin were measured as well as changes of the pancreatic histology were examined by light and electric microscope in 6h, 12h, 24h after operation. Results as compared with control groups , amylase and endotoxin in AHNP group were significantly higher in the plasma and the damage to pancreatic tissue was increased in severity as observed with light and electric microscopes in 6h, 12h, 24h after operation. Comparison between NTX treatment groups with AHNP groups demonstrated that amylase and endotoxin were significantly decreased in the plasma, and the damage to pancreatic tissue was reduced in NTX treatment phase. Conclusion these results showed that endotoxemia was induced by AHNP, but NTX decreased the edotoxin level in the plasma and improved the damage of pancreatic tissue. The lethality was significantly lowered and average survival time was prolonged during NTX treatment of AHNP.