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)
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 the histopathologic features and expression patterns of tumor necrosis factor-alpha; （TNF-alpha;）, interleukin-1beta;（IL-1beta;） and Escherichia coli lipopolysaccharide (LPS) in the rat vitreous with LPS inducedendophthalmitis. Methods Wistar rats were randomly divided into saline control group (SC,136 rats）,endophthalmitis group （EO, 168 rats）and blank control group （BC,12 rats）.EO group received an intravitreal injection of 5 mu;l LPS; SC group received 5 mu;l sterile saline and no intervention for BC group.Six,12,24,48, and 72 hours,5 and 7 days after injection, intraocular inflammation were observed and the eyes and vitreous were collected for histopathological examination and measurement of TNF-alpha;, IL-1beta; and LPS expression. Results Severe inflammatory responses in the eyes were observed in EO group between six and 72 hours after LPS injection，ocular inflammation subsided seven days after LPS injection. In the vitreous, a peak neutrophil count was observed at 24 hours （1224.64plusmn;132.2） cells/eye that rapidly declined at 72 hours （342.25plusmn;47.7） cells/eye. The levels of TNF-alpha; and IL-1beta; in EO group were peaked at 24 hours with （996.18plusmn;89.45） and（5556plusmn;1440）pg/ L, respectively；Persisted at 48 hours and began to decline rapidly thereafter. Seven days after LPS injection, levels of TNF-alpha; and IL-1beta; returned to baseline with （22.16plusmn;5.84）and （73.7plusmn;18.7） pg/L, respectively. LPS concentration in EO group decrease rapidly at 72 hours with （11.03plusmn;3.41） ng and disappear on days 7 with (0.22plusmn;0.08) ng after LPS injection.Conclusions Massive neutrophils infiltration, high levels expression of TNF-alpha; and IL-1beta; and spontaneous elimination of bacterial elements in vitreous cavity were major pathologic characteristics in this experimental model. The expression patterns of TNF-alpha;,IL-1beta; were in accord with LPS clearance process.
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 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)
ObjectiveTo explore the effect of endotoxin on insulin secretion from islet βcell of rat pancreas.MethodsAfter the model of endotoxemia was established in rats with intraperitoneal injection of LPS (2 mg/kg),the changes of insulin level in the serum and pancreas were dynamically determined, the expression of inducible nitric oxide synthase (iNOS) by situ hybridization and DNA damage in islet cells were also observed, the effect of sodium nitroprusside (exogenous NO) on synthesis and secretion of insulin from isolated islet βcell of normal rat pancreas under high glucose stimulation was also evaluated.ResultsThe level of glucose and insulin in plasma were significantly increased at 12th and 6th h, respectively and kept on 3 d after injection of LPS,but the insulin level in pancreas was not remarkably altered.The expression of iNOS and DNA damaged significantly enhanced at 6 d after endotoxemia. The high glucosestimulated insulin synthesis and secretion were bly inhibited by exogenous NO.ConclusionThese findings suggest that LPS be stimulate the expression of iNOS and NO product,which inhibites synthesis and secretion of insulin in islet βcells,but it stimulates insulin secretion by another mechanism,and results in dysfunction and destruction of the rat pancreas.
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 observe the change in plasma endotoxin and cytokine during the early period of intra-abdominal infection (IAI) complicated by multiple system organ dysfunction (MSOD) in animals. Twenty rabbits were randomly divided in to two groups. One group received the operation of cecal ligation plus puncture (CLP) inducing IAI complicated by MSOD, and another group received sham operation as a control. All animals were placed in metabolic cages and maintained with intravenous infusion for one week. Plasma levels of endotoxin and cytokine (TNF, IL-1, IL-6) were determined seperately at the beginning (0 hour) or 1, 2, 3, 4, 5, 6 and 24 hours after CLP. Blood bacteria cultures and pathological examination of several organs were made when the animal was dead or killed. Results: The levels of plasma endotoxin, TNF and IL-6 were found to be significantly increased at one or two hours after CLP, the incidence rate of bacteriemia was 80% and the pathological alterations in the abdomen and organs were remarkale, with an average survival time of 84.1±39.0 hours in CLP group. No change in plasma IL-1 level was found in the CLP group. Conclusion: The plasma levels of endotoxin and cytokine (TNF and IL-6) do increase in the early period of IAI complicated by MSOD, and the change in plasma IL-1 is not obvious.
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.