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)
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.
【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.
This study based on two serial animal experiments: ①caerulein-induced edematous pancreatitis with gut motility inhibited by administration of lopemin (an opium antidiarrheal agent) and ②deoxycholate intraductal-injection induced pancreatitis with gut motility improved by administration of rhubarb solution. The results of these experiments indicated that inhibition of gut motility will increase the incidence of bacterial translocation and endotoxemia during acute pancreatitis; and acceleration of gut motility will significantly decrease the incidence of bacterial translocation and endotoxemia during severe type of acute pancreatitis. The authors conclude that promotion of gut motility may protect the inflammatory pancreas from infection and prevent the multiple organ failure during acute pancreatitis, and eventualy improve the prognosis of pancreatitis.
ObjectiveTo investigate the changes of diamine oxidase(DAO) and endotoxin(ET) during the treatment of systemic inflammatory response syndrome with human growth hormone and the relationship between human growth hormone and intestinal mucosal barrier injury. MethodsOne hundred and fortysix patients with systemic inflammatory response syndrome were randomly divided into operative group and nonoperative group, which were again randomly divided into the study group and control group.Plasma concentration of DAO and ET were determined before the treatment and 1 week after the treatment.ResultsPlasma concentration of DAO and ET in study group decreased after treatment with significant difference (P＜0.05，P＜0.01).ConclusionHuman growth hormone can protect intestinal mucosa barrier.
Objective To study endotoxin release induced by differential antibiotics in gram negative bacterial infection. Methods Thirty critical patients accompanied with gram negative bacterial infection were divided into group A (imipenem group, n=15) and group B (ceftazidine group, n=15). Imipenem (0.5 g iv q8h) and ceftazidine (1.0 g iv q8h) were given respectively. White blood cell (WBC), systolic blood pressure (SBP), lipopoly sacchride (LPS), tumor necrosis factor alpha (TNFα) and high density lipoprotein (HDL) were determined in 0, 1, 2, 3, 5 and 7 day. Results There was no difference in the change of WBC between two groups. Group A had a more stable SBP than group B. There was lower endotoxin release in group A than in group B and so were the cytokines release. HDL level was lower in group B than in group A. Conclusion Imipenem has lower endotoxinliberating potential than ceftazidine and mediate lower cytokines release. HDL may protect the patients from LPS damage.
Objective To investigate the effects of expression of TNFα mRNA on glucose uptake in both the liver and skeletal muscle after endotoxemia. Methods In the mice with intraperitoneal injection of lipopolysaccharide (LPS), the changes of TNFα level of plasma and uptake of 2-deoxyglucose (2-DG) in the isolated soleus muscle and hepatic tissues were determined, then the reinstatement of glucose uptake by injecting TNF-McAb for 3 days was also observed. In addition, changes of TNFα mRNA expression of liver were evaluated. Results The expression of TNFα mRNA in the liver showed markedly increased in the first 3 hours post endotoxemia and remaind high for 3 days, and the plasma TNFα level paralleled with TNFα mRNA expression of liver also was elevated. The basal uptake of 2-DG both in muscle and liver were markedly increased, but the stimulated 2-DG uptake with insulin was greatly reduced as compared with the control. In addition, these abnormalities of 2-DG uptake can be partially corrected by neutralization of the circulatory TNFα by administration of TNF-McAb. Conclusion The disorders of glucose uptake of the liver and the muscle due to the overexpression of TNFα mRNA and elevated circulatory TNFα level may be the mechanism of insulin resistance after endotoxemia.
The purpose of this study was to determine the contribution of endotoxin (ET) in ocurrence and progression of acute pancreatitis (AP). The results indicated that correlation of ET changes with multiple organ damage in AP. The degree of ET elevation correlated well with the severty of AP. The level of plasma ET of severe AP patients was much higher than that of mild AP patients (Ｐ＜0.05). The chance of multiple organ damage got greater while the plasma ET level got higher. Moreover, the severety change of severe AP correlated with the change of plasma ET level. In other words, the ET level was reduced while the disease was recovering, elevated while it was becoming worse and maintained high level in dead cases. We think that plasma ET level can be used as a reference for differenciating mild AP with severe AP and a predictor for the prognosis of AP.
Objective To research the changes in plasma endothelin, LPS, TNF-α, IL-6 and IL-8 in the patients with obstructive jaundice (OJ) and non-obstructive jaundice (NOJ) after surgery. Methods The plasma ET, LPS, TNF-α, IL-6 and IL-8 were measured in 15 patients without jaundice as controls. Results As compared with NOJ, the postoperative changes of ET, LPS, TNF-α, IL-6 and IL-8 in OJ group increased significantly at multiple time points (P＜0.05). Conclusion There is interaction between ET,LPS, TNF-α, IL-6 and IL-8 and damage to multiple organ function in patients with OJ after surgery.