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《Journal of Clinical Rational Drug Use》 2011-29
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Explore the Effection and Machanism of Different Doses of Ulinastatin in Septic

CHEN Xiao-bing,XU Tie,LI Xiao-min,et al.Center of Emergency,First People's Hospital of Lianyungang,Affiliated Hospital Xuzhou Medical College,Lianyungang 222001,China  
Objective To observe the changes of tumor necrosis factor-a(TNF-a)、inter-leukin-6(IL-6)in plasma and the expression of nuclear factor-KappaB(NF-κB)in lungs in rabbits with septic shock induced by endotoxin,and to explore the prote-ctive the effection and mechanism of different doses of Ulinastatin(UTI).Methods 50 male Japanese flap-eared white rabbits were randomly divided into 5 groups:Endotoxin induced septic shock control group(group con),Dexamethasone treated group(group DXM),(2.5×104)u/kgUTI treated groups(group U1)、(5.0×104)u/kgUTI treated groups(group U2)and(10.0×104)u/kgUTI treated grou-ps(group U3).Septic shock models of the rabbits were replicated by intravascularET injection(2mg/kg).Then 0.9% physiological saline(2.0ml),DXM(1.0mg/kg),and UTI in doses of(2.5×104)U/kg、(5.0×104)U/kg,and(10.0×104)U/kg were respectivel-y given in 2.0ml 0.9% physiological saline after the septic shock models wereset up.At oh after shock and 2h、4h、6h、12h after treated,The changes of me-an arterial blood pressure(MAP)and Respiratory Rate(RR)were determined,The levels of TNF-a and IL-6 in plasma of the rabbits were measured by using E-LISA;The morphological changes of lungs were observed under microscope,The expression and distribution of NF-κB in rabbits'lungs were detected by immun-ohistochemistry.Results The levels of MAP、RR and TNF-a、IL-6 at oh after the septic shock showed not significant difference among the five groups,however,the levels of MAP、RR and TNF-a、IL-6 at 2h、4h、6h、12h in the three UTI group were significant decreased as compared with group con and group DXM(P0.05),and group U3 were lower than group U1 and group U2(P0.05);The mor-phological changes of lungs in group Con were the most obvious,group U3 wer-e the lightest as compared with other groups(P0.05).The expression of NF-κB in group Con was the most obvious,groupU3 was the lightest as compared wi-th other groups(P0.05).The leveles of MAP、RR and TNF-a、IL-6 and the ex-pression of NF-κB were degraded with the increasing doses of UTI(P0.05).Conclusion UTI can improve the changes of MAP、RR and TNF-a、IL-6 in septic shock induced dy ET in rabbits and the lung protective function is the positive correlation with the dosage.Inhibiting NF-κB signal transduction pathwa-ys to inhibit the expression of TNF-a and IL-6 is one of UTI lung protective function important mechanisms.
【CateGory Index】: R965
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