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Effect Of Ketamine On Myocardium Expression Of NF-κB And Serum IL-6,TNF-α Level In Ischemia-reperfused Rats

Posted on:2005-03-03Degree:MasterType:Thesis
Country:ChinaCandidate:J WuFull Text:PDF
GTID:2144360125956238Subject:Anesthesia
Abstract/Summary:PDF Full Text Request
Objective Inflammatory response plays important role in myocardium ischemia-reperfusion injury which is a common pathophysiological change in clinical anesthesia. Nuclear transcription factor-kappaB (NF- B) is the mediator of many inflammatory factors, and has important effects on ischemia-reperfusion injury. It has been reported that ketamine canreduce the inflammatory factors(TNF- a ,IL-6)level,but it is not clear about the effects of ketamine on ischemia-reperfusion myocardium . Therefore, in this study, we investigated the effects and possible mechanism of ketamine on myocardial expression of NF- B and serum IL-6, TNF- levels inischemia-reperfused(I/R)rats model. Methods 24 healthy SD male rats, weighing 200-250g ,were anesthetized with 10% chloral hydrate and ventilated via a tracheostomy on an animal respirator with tidal volume of 2ml/100g and respiratory rate of 60 breaths per minute). The 4th left rib was cut and a model of left coronary artery(LCA) occlusion/release was carried outo Rats were divided randomly into 4 groups: control group without LCA occlusion (group A, n=6);I/R group(group B, n=6); ketamine(5mg.kg-1)+I/R group (group C, n=6); ketamine(10mg.kg-1) +I/R group(group D,n=6)o All rats in groups B, C , D were subjected to 30 minutes of LCA occlusion followed by 120minutes of reperfusion. Rats in group C and D were injected with 5mg.kg-1 and 10mg.kg-1 of ketamine before reperfusion, respectively. Significant electrocardiogram and color changes at the area at risk were considered indicative of successful coronary occlusion and reperfusionc Serum was exampled from left jugular vein at 30 minutes and 120 minutes during reperfusion to measure IL-6 and TNF- level by ELISA measurements. After reperfusion of 120 minutes, the heart was removed and the cardiac apex was exampled with snap-frozen in liquid nitrogen and stored at -70 C .The NF- B level in the myocardium was measured by Western-blot analysis. Results 1.The effects of ischemia-reperfusion on myocardial NF- K B production and serum IL-6 level: The expression of myocardial NF- B was 28.97 10-2 in group B, higher than that in groupA(12.81 10-2); The serum IL-6 levels in group B at reperfusion of 30minutes and 120 minutes were168 pg ml-1and 180 pg ml-1 .which were higher than those in group A(134 pg ml-1 and 142 pg ml-1); The serum TNF-a levels of group B at reperfusion of 30minutes and 120 minutes were 1.33ng ml-1and 1.40ng.ml-1 ,which was high than those in group A(0.61ng ml-1and 0.65 ng ml-1 )(P < 0.01); 2. The effect of ketamine on NF- к B and serum IL-6, TNF-a in ischemia-reperfusion myocardium. The expression of myocardial NF- к B in groups C and D(22.99 10-2 and 16.49 10-2) were higher than that in group A (P < 0.01), and lower than that in group B (P < 0.01), The expression of myocardial neuronal NF- к B in group D was lower than that in group C (P < 0.01);The serum IL-6 level in groups C(152 pg ml-1and 174 pg )and D(140 pg ml-1 , 156 pg ml-1) at reperfusion of 30 and 120 minutes were higher than those in group A, respectively (P < 0.01),lower than those in group B (P < 0.01), The serum IL-6 level in group D at reperfusion of 30 and 120 minutes were lower than those in group C(P < 0.05) . The serum TNF-a level of groups C(1.01ng ml-1 and 1.06 ng ml-1) and D(0.82ng ml-1and 0.86 ng ml-1)t reperfusion of 30 and 120 minutes were higher than those in group A ,espectively,lower than those in group B (P < 0.01), The expression of serum TNF-a group D at reperfusion of 30 and 120 minutes were lower than those in group C(P < 0.05). The expression of myocardial neuronal NF- K B is obviously related to serum IL-6 level(r=0.950)(P<0.05)and serum TNF-a level(r=0.958) (P<0.05). Conclusion Ischemia-reperfusion could induce the expression of myocardial NF- K B and serum IL-6, TNF-a secretion, Ketamine could reduce the expression of NF- K. B and serum IL-6 , TNF-a level in ischemia-reperfused myocardium and suppress inflammatory response induced by ischemia-reperfusion.
Keywords/Search Tags:NF- kappa B, Interleukin-6, TNF-α, Myocardial reperfusion injury, Ketamine
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