摘要
目的观察内毒素(ET)致感染性休克兔血浆中肿瘤坏死因子-a(TNF-a)、白介素-6(IL-6)和肺组织核转录因子-κB(NF-κB)水平变化,研究不同剂量乌司他丁(UTI)对感染性休克兔肺损伤的保护作用及其机制。方法将50只健康日本长耳大白兔随机分为ET致休克模型组(对照组),地塞米松(DXM)干预组(DXM组)及三种不同剂量UTI干预组(U1组、U2组、U3组3个亚组),每组10只。采用ET(2mg/kg)一次性静脉注射方法复制兔感染性休克模型,造模成功后对照组应用0.9%氯化钠溶液2ml,DXM组用DXM(1mg/kg)、U1组用UTI(2.5×104)U/kg、U2组用UTI(5.0×104)U/kg、U3组用UTI(10.0×104)U/kg分别溶于2ml0.9%氯化钠溶液静脉注射进行干预,监测兔的平均动脉血压(MAP)和呼吸频率(RR)的变化,检测休克0h和干预后2h、4h、6h和12h等时间点血浆中的TNF-a、IL-6水平,HE染色观察肺组织病理形态学变化,免疫组化染色检测肺组织NF-κB的表达。结果在0h,5组兔的MAP、RR及TNF-a、IL-6水平差异无统计学意义(P>0.05);3个UTI亚组与对照组及DXM组在休克后不同干预时间点MAP、RR及TNF-a、IL-6水平比较,差异均有统计学意义(P<0.05);肺组织病理变化在对照组肺损伤最强,U3组最轻,差异有统计学意义(P<0.05);NF-κB在肺组织的表达在对照组最强,U3组最轻,差异有统计学意义(P<0.05)。MAP、RR及TNF-a、IL-6的水平和NF-κB表达在3个UTI亚组间随着UTI剂量的加大,差异均有统计学意义(P<0.05)。结论 UTI能改善ET所诱导的感染性休克兔的MAP、RR和TNF-a、IL-6的变化,尤以大剂量改善效果更明显。UTI对ET所诱导的感染性休克兔肺损伤有明显的保护作用,且UTI的肺保护作用与剂量成正相关性。通过抑制NF-κB信号转导通路抑制TNF-a和IL-6的表达是UTI肺保护作用的重要机制之一。
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 × 10^4） u/kgUTI treated groups （group U1 ）, （5.0× 10^4） u/kgUTI treated groups （ group U2 ） and （ 10. 0 ×10^4 ） u/kgUTl treated grou - ps （ group U3 ）. Septic shock models of the rabbits were replicated by intravaseularET injection （2mg/kg）. Then 0. 9% physiological saline （2. 0ml） , DXM （ 1.0mg/kg）, and UTI in doses of （2. 5 × 10^4） U/kg, （5.0 × 10^4） U/kg, and （ 10.0 × 10^4） 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 plas- ma 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 （ P 〈 0.05 ）, and group U3 were lower than group U1 and group U2 （ P 〈 0. 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 （ P 〈 0.05 ）. The expression of NF - κB in group Con was the most obvious, groupU3 was the lightest as compared wi - th other groups （P 〈 0.05 ）. 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 （P 〈 0.05）. Conclusion UTI can improve the changes of MAP, RR and TNF - a, IL - 6 in septic shock in- duced 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.
出处
《临床合理用药杂志》
2011年第05X期8-13,共6页
Chinese Journal of Clinical Rational Drug Use
作者简介
通讯作者：李小民，222001江苏连云港第一人民医院急救中心；E—mail：wylwjc123456@163．com
