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Objective To investigate the changes of NGF mRNA expression and the effect of exogenous interleukin 1?(IL 1?) on it in rats after traumatic brain injury(TBI) and to explore the mechanism of NGF and IL 1? in TBI. Methods A brain trauma model of fluid percussion in rats was established. Changes of NGF mRNA expression and effect of exogenous IL 1? on it were observed by RT PCR, molecular hybridization and immunocytochemical techniques. Results NGF mRNA expression in the brain injury site and tissues adjacent to it began to increase at 12 h after trauma and increased markedly at 24 h and reached the peak value on the 3rd. Then it decreased gradually, but still higher than that of the control. NGF mRNA expression increased at 3 h after trauma in IL 1? treatment group and was significantly higher than that in simple trauma and control groups( P
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Objective To investigate the effect of cellular membrane phospholipids on CD14 protein expression of macrophage stimulated by LPS. Methods Changes of CD14 protein expression and CD14 mRNA of macrophages stimulated by LPS in vitro were determined by Western blotting and RT PCR. Effects of membrane phospholipids on CD14 protein expression were also detected. Results After stimulation by LPS, CD14 expression increased at 1 h, reached the peak value at 5 h and decreased to the normal level at 8 h but CD14 mRNA reached the peak value at 3 h and decreased at 5 h. The levels of phospholipids and membrane fluidity decreased at 5 h but CD14 protein expression increased after LPS stimulation. After pretreatment with liposomes, membrane phospholipid microenvironment improved and CD14 protein expression decreased. Conclusion LPS can up regulate CD14 protein expression, which might be regulated at least at the transcriptional level of the CD14 gene. Changes of membrane phospholipid microenvironment may be an important reason for the up regulation of CD14 induced by LPS.
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<p><b>OBJECTIVE</b>To study the mechanism of macrophage injury after trauma-hemorrhagic shock.</p><p><b>METHODS</b>Wistar male rats underwent trauma (closed bone fracture) and hemorrhage (mean arterial blood pressure of 35 mm Hg+/-5 mm Hg for 60 minutes, following fluid resuscitation). Rats without trauma, hemorrhage or fluid resuscitation served as controls. Peritoneal macrophages were harvested at 6 hours and 1, 2, 3, 7 days after traumatic hemorrhagic shock to determine the effects of pertussis toxin (PTX, as a specific inhibitor to Gi(alpha) and cholera toxin (CTX, as a stimulant to Gs(alpha) on macrophage-Ia expression and TNF-alpha production and levels of Gi(alpha) and Gs(alpha).</p><p><b>RESULTS</b>The macrophages from the injured rats revealed a significant decrease of Ia positive number and TNF-alpha release in response to LPS. Wi th pretreatment with PTX 10-100 ng/ml Ia positive cells and LPS-induced TNFalpha production in both control and impaired macrophages populations were dos e dependently increased. Both macrophages populations were not responding to CTX treatment (10-100 ng/ml). Western blot analyses showed that the levels of Gi(alpha) protein expression increased as much as 116.5%-148.8% of the control level fro m 6 hours through 7 days after traumatic hemorrhage. The levels of Gs protein expression were reduced at 6 hours and decreased to the lowest degree; 36% o f the control at day 1, began to return at day 2 and returned to the normal level at day 7, following traumatic hemorrhagic shock.</p><p><b>CONCLUSIONS</b>PTX-sensitive G-protein may participate in th e modulation of macrophage-Ia expression and TNF-alpha release following traumatic hemorrhagic shock. Analyses of the alteration of Gi(alpha) and Gs protein express ions further supports the concept that G-protein is involved in trauma-induced macrophage signal transduction pathways.</p>
Subject(s)
Animals , Male , Rats , Analysis of Variance , GTP-Binding Proteins , Allergy and Immunology , Metabolism , Histocompatibility Antigens Class II , Allergy and Immunology , Immunoblotting , Lipopolysaccharides , Pharmacology , Macrophages, Peritoneal , Allergy and Immunology , Metabolism , Rats, Wistar , Shock, Hemorrhagic , Blood , Allergy and Immunology , Signal Transduction , Tumor Necrosis Factor-alphaABSTRACT
OBJECTIVE: To observe effect of endothelin-1 (ET-1) on hepatic damage induced by endotoxin. METHODS: A total of 90 rats were randomly divided into control group (group C), endotoxin treated group (group LPS) and endotoxin plus ET-1 antibody treated group (group LEA). An observation was done on the changes of ET-1 concentration, and transcription and expression of ET-1 mRNA. Plasma glutamic pyruvic-transaminase enzyme (GPT), hepatic lactate dehydrogenase (LDH), adenosine triphosphate (ATP) and malondialdehyde (MDA) were also observed at 3, 6, 9, 12, 24 hours after saline, endotoxin (10 mg/kg) and ET-1 antibody (dalubine 1:2000, 2 ml/kg) administration. RESULTS: The results indicated that the concentration of plasma and hepatic ET-1 and expression of ET-1 mRNA in liver significantly increased following endotoxemia. The hepatic ET-1 levels were inversely correlated with the ATP concentration, and positively related to the MDA concentration. ET-1 antibody could partially protect the liver against damage induced by endotoxin. CONCLUSIONS: These results suggest that endotoxin may, on transcription and translation level, lead to an increase of ET-1 in synthesis. ET-1 may contribute to hepatic damage during endotoxemia.
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OBJECTIVE: To elucidate which one of &mgr;, delta and kappa opioid receptors is involved in the cardiovascular depression following traumatic hemorrhagic shock. METHODS: With traumatic hemorrhagic shock rat models, the changes of myocardial and brain &mgr;, delta and kappa opioid receptors and cardiovascular functions and their relationship with hemodynamic parameters were observed. The effects of delta and kappa opioid receptor antagonists on hemodynamic parameters of traumatic hemorrhagic shock rats were observed. RESULTS: Following traumatic hemorrhagic shock, the number of myocardial and brain delta and kappa opioid receptors significantly increased, their affinity did not alter, and the increased number of delta and kappa opioid receptors was significantly associated with the decreased hemodynamic parameters. However, &mgr; opioid receptor in heart and brain did not obviously change. delta opioid receptor antagonist ICI174,864 and kappa opioid receptor antagonist Nor-binaltorphimine (50 &mgr;g, Icv) could significantly reverse those decreased hemodynamic parameters. CONCLUSIONS: It suggests that opioid receptors, especially delta and kappa opioid receptors are closely related to the pathogenesis of traumatic hemorrhagic shock, and they play important roles in the depression of cardiovascular function following traumatic hemorrhagic shock.
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Blood transfusion is still an imperative and effective therapeutic remedy for many diseases, especially for trauma and shock. But the donation of blood by healthy citizens is seriously inadequate, and, more recently, blood transfusion is a matter of great concern because of viral infections such as hepatitis and HIV. In addition, blood transfusion has some other limitations including difficulty of storage and transportation, and needing cross-matching because of blood group antigens. Thus, the development of an oxygen carrier, which could serve as a safe and effective alternative to human blood or red blood cell (RBC), has gained great interest worldwidely.
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The cableway for the evacuation of the wounded is simple in structure,light in weight,and quite easy to be assembled and disass- embled.It is a perfect way not only for the evacuation of the wounded in the junglle and hilly zones but also for transport of light weaponry and means of livelihood?The cable way,particularly,can function distinctively wherever stretchers and modern conveyances are quite Iimited especially in the mountains,valleies or rivers.In addition,it is also a safe and rapid way to evacuate iarge puantities of the wounded group by group,Therefore it can enhance the efficiency ten times to thirty times.
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Thyrotropin releasing hormone (TRH) and naloxone were compared in their antagonism to the effects of analgesia,addicton-induction,movement restatraining,respiration depression,LD50:etc of morphine.It was found that TRH was entirely different from naloxone in that it was not antagonistic at all to the morphine effects mentioned above.So TRH would be a better choice than naloxone in the treatment of traumatic shock.
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Objective:To study the specific photochemical effects of a newly designed target photosensitizer. Methods Based on the technique of antisense nucleic acid and the principle of photochemical reaction effects,a specific sensitizer,TFO P has been designed and synthesized.When in coordination with long wave ultraviolet ray(UVA) ,this decorated complex (TFO P) was added into the blood cell suspension to inactivate the contaminating virus( duck hepatitis virus B,DHBV).The efficacy of specific binding to DHBV DNA and viral inactivation by TFO P was detected by gel shift blot assay and infection of primary culture of duck hepatocyte.Results The designed TFO P could specifically bind to different DHBV DNA line sample and present different linking level.With a TFO P concentration of 0.1 nmol/ml and UVA intensity of 1800 ?W/cm 2,the DHBV in blood cell suspension could be reduced by 1.90～5.40 logs.Conclcusion The photochemical effects of TFO P could significant inactivate DHBV in blood.
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It was found that after 2 dosages of Pseudomonas aeruginosa suspension(7?109/kg and 2?1010/kg)were infused to rabbits respectively to induce septicemia,the elevation of the tumor necrosis factor(TNF)level in the circulating blood was higher in 2?1010/kg group than in 7?109/kg group.The dynamic changes of circulation TNF in P.aeruginosa septicemia were different from those in endotoxin shock.There was a continous increase of plasma glucagon,Iactic acid and ?-G(P
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The effects of oxygen-derived free radicals on the lipid peroxidation injury of the hepatic subcellular organelles were observed in rats after they were inflicted with endotoxic or hemorrhagic shock.It was found that in the early stage of shock,the content of malondialdehyde(MDA)of hepatic mitochondria and lysosome suspension were significantly increased(P
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Changes of hepatic mitochondrial respiratory function and the protective effects of several free radical scavenging enzymes or drugs on the mitochondrial functions were observed after superior mesenteric artery occlusion shock was inflicted to the rat.It was found that there was an obvious decrease of respiratory control rate (RCR) in the 1st hour after the occlusion was released and a further decrease in the 2nd hour,and P/O value decreased significantly at the same time,which indicates that mitochondrial dysfunction does occur.in the shock due to superior mesenteric artery occlusion.However,RCR ard P/O value did rot significantly decrease in the 1 st hour after occlusion releasing in the treated groups with allopurinol (ALLO),a combination of catalase (CAT) and superoxide dismutase (SOD),a combination of SOD and ALLO,and a combination of SOD,ALLO,and CAT as compared with those of the control,and were markedly higher as compared with those of the experimental group.In the 2nd hour after occlusion releasing,RCR of the ALLO treated group was significantly lower than that of the control and remained significantly higher than that of the experimental group.The average survival time of the animals was much longer in the treated groups than in the experimental group.Our findings demonstrate that free radical scavengers,SOD,CAT,and ALLO especially a combinaton of them can exert protective effects of different degrees on the mitochondrial respiratory function during a shock due to superior mesenteric artery occlusion.
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The effects of endlbtoxin on lipid peroxidation injury of rat hepa-tocytes and the protective effects of exogenous superoxide dismutase (SOD) were studied in vitro.It was found that after the isolated rat hepatocytes and endotoxin (500 ng/ml) were incubated together for 6 hours,there was an obvious increase of malondialdlehyde (MDA) level and lactic dehydrogenase (LDH) and SOD activities,and the increase of LDH and SOD activities occurred earlier than that of MDA level.Polymorphonuclear neutrophils (PMN) after activated by endotoxin could destroy the hepatocytes and increase MDA level and LDH and SOD activities which could partially be inhibited with the pretreatment of exogenous SOD.These findings suggest that endotoxin can intensify the injurious effects of PMN on hepatocytes and it can also directly induce lipid peroxdatipn injury on hepatocyes but the mechanism was not clear.
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After intravenous infusion of recombinant human tumor necrosis factor(TNF)in the dosage of 60?g/kg or 130?g/kg to rabbits,it was found that their plasma malondialde-hyde(MDA)was significantly increased(P
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A model of traum a shook was established in rats by comminutedly fracturing of the right femur and bleeding of 15% of the body weight.In the 1st hour after injury,the content of malondialdehyde (MDA) of the heart and the lungs increased,the activity of sv.peroxide dismutase (SOD) in the lungs decreased,and the MDA content and SOD activity in hepatic mitochondria increased synchronously.In the 3rd hour after injury,the MDA content increased not only in the heart,the lungs and hepatic mitochondria but also in the liver and the kidneys,and the SOD activity increased in the heart,the kidneys and the intestinal tract but decreased in hepatic mitochondria.There were further marked elevation of MDA content and progressive inhibition on SOD activity in the 5 vital organs and hepatic mitochondria in the 5th hour after injury.When shock continued to progress,the plasma MDA content increased gradually,the SOD activity of the hemolytic blood decreased,and the activities of plasma acid phosphatase and ?-glucuronidase,the indicators of lysosome destruction,increased markedly.These findings suggest that the oxygen-derived free radicals are responsible for the damages to cells of the vital organs and subcellular organelles during traumatic shock.
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No. Ⅱ fluorocarbon blood substitute in divided doses was infused into the rats in a 12-day-period. Pathomorphological changes of the various organs of the animals were observed dynamically in the first year after the completion of the infusion. Fluorocarbon particles mainly accumulated in the organs with abundant reticulo-endothelial tissue particularly the liver and spleen. The changes of the weight of the liver and spleen and the existence of foam cells could be considered as the criteria to indicate the severity of the accumulation. It was found that at the end of the first year after the completion of No. Ⅱ fluorocarbon blood substhue infusion, the liver and spleen essentially resumed their normal weight but a small number of foam cells still existed, However, accumulated fluorocarbon particles exerted no harmful effects on the functions and structures of the organs observed.
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Endothelial cells (EC) from human umbilical vein have been subcultured for 10 passages as identified with optical and electron microscopy.The modulation effects of recombinant human tumor necrosis factor (rHTNF and TNF) on the 1st to 3rd generation of ECs in their synthesizing tissue factor were studied.It was found that when rHTNF and ECs were cocultured to the 4th hour,the activity of the tissue factor synthesized by ECs was significantly elevated (P