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Thymosin ¦Â4 Experimental Study Of The Treatment Of Endotoxin Shock

Posted on:2006-03-04Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y G ZhaoFull Text:PDF
GTID:1114360155451092Subject:Surgery
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Objective:To explore the mechanism of action of thymosin β4 (Tβ4) in septic shock by observing the 72h survival rate of septic shock mice treated with thymosin β4. Methods: 1,The Tβ4 between normal and septic shock mice were determined. 2,The survival rate of septic shock mice was studied by intraperitoneal injection of Tβ4. 3,The survival rate of septic shock mice was studied treated by different dose Tβ4 in 72h . 4,The survival rate of septic shock mice was studied treated by different dose Tβ4 in 72h. Results: Tβ4 was obviously decreased in the blood of septic shock mice. Tβ4 could raise the 72h survival rate of septic shock mice,which have relationship with the injected dose and injected time. Conclusion:The optimal protective methods in the mouse appears to be 5mg/kg Tβ4 given immediately following(0h) and at 2h and 4h successively post LPS. Objective:In order to study the mechanism of Tβ4 in the body,we performed our work in: 1.vital signs of the body;inflammatory mediators 2.changes of the lung 3.changes of the brain. Methods: Experiment one: Effect of Tβ4 on vital signs of the body and inflammatory in endotoxin-induced septic shock. One:Animal model SD rats were divided into three groups of 15 each:normal control group(Group N); LPS group(Group L); LPS + Tβ4 group(Group T). We recorded the MAP,HR and RR in femoral artery post weighing and anesthesia.Group L and Group T were received LPS(10mg/kg) through femoral vein.Group T were injected Tβ4(5mg/kg) at 0h,2h,4h successively post LPS.Group N received the same dose saline. Two:Content of observation 1,Vital signs of the body:We recorded three groups' MAP,HR,RR at 0,30,60,90,120,180,240 minute post LPS. 2,TNF-α,NO,IL-1β:We measured the blood levels of TNF-α,NO,IL-1β at 6 hour post LPS. Experiment two: Effect and mechanism of Tβ4 on changes of the lung in endotoxin-induced septic shock. One:Animal modelSD rats were divided into three groups of 30 each.Animal model was same as experiment one. Two:Content of observation 1,lung body index 2,water contained in the lung 3,counting leucocyte in bronchoalveolar lavage fluid(BALF) 4,blood gas analysis 5,measurement of protein in BALF 6,measurement of MPO in lung tissue 7,measurement of TNF-αmRNA and IL-1βmRNA through RT-PCR; half ratio Analysis of PCR results Experiment three: Effect and mechanism of Tβ4 on changes of the brain in endotoxin-induced septic shock. One:Animal model SD rats were divided into three groups of 15 each.Animal model was same as experiment one.The brains were taken out from three groups rats post LPS 6h. Two:Content of observation 1,brain body index 2,measurement of NO in the brain tissue 3,measurement of SOD in the brain tissue 4,measurement of MDA in the brain tissue 5,measurement of Ca2+ in the brain tissue Results: 1,Tβ4 could make vital signs of the body better,such as MAP,HR,RR.It also could down-regulate the blood levels of TNF-α,NO,IL-1β.2,Tβ4 could make the injury of lung lighter,which showed that LBI and water in lung decreased,PaO2 rised,leucocyte reduced in BALF,MPO reduced in lung tissue. Besides the expression of TNF-αmRNA and IL-1βmRNA was lower in Group T than in Group L. 3,Tβ4 could make the injury of brain lighter,which showed that brain body index,MDA,NO,Ca2+ decreased and SOD rised in brain. Conclusion: 1,Tβ4 can make vital signs of body better and down-regulate the inflammatory mediators. 2,Tβ4 can improve the injury of lung in endotoxin-induced septic shock. 3,Tβ4 can improve the injury of brain in endotoxin-induced septic shock.Objective:In order to study the effect of thymosin β4 in endotoxin induced septic shock Methods: Experiment one:Tβ4 reduced the activation of NF-κB and down-regulated TNF-α in PBMC induced by LPS in vitro. 1,Collection of PBMC 2,Culture of Cells Cells were divided into three groups:normal group,LPS group(10μg/ml),Tβ4 group(10μg/ml LPS +Tβ4:final concentration 100μM).Thr...
Keywords/Search Tags:NF-κB, Apoptosis, Tβ4, LPS, TNF-α, IL-1β, Thymosin β4, Survival rate, Septic shock
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