摘要
目的:通过观察CPU0213对感染性休克大鼠血管活性的改善,探讨其治疗感染性休克可能的作用机制。方法:感染性休克大鼠术后8 h皮下给予CPU0213(30 mg.kg-1,bid×3 d)。记录存活率,血流动力学参数,器官脏器系数和腹腔渗出液重量,检测血浆ET-1和血清iNOS、GSH-PX、SOD、MDA含量及胸主动脉血管活性,肠系膜血管NF-κB、TNF-αi、NOS和ET系统mRNA表达及其激活态NF-κB蛋白表达。结果:模型组大鼠存活率和平均动脉压明显降低,心率和器官脏器系数明显增加,腹腔渗出液显著增多,ET-1和iNOS、MDA含量明显增加,GSH-PX和SOD活性显著下降,血管功能明显降低,TNF-αi、NOS和ET系统mRNA表达及NF-κB的蛋白表达明显增加;CPU0213治疗后,上述指标均有不同程度改善。结论:CPU0213通过阻断ET系统和NF-κB通路改善血管活性,减少腹腔渗出液,提高存活率。
AIM： To study the amelioration of blood vessel and mechanism of a non-selective ETA/ETB receptor antagonist （CPU0213） on cecal ligation and puncture （CLP） rats.METHODS： After 8 hours at CLP, the rats were subcutaneouly administered with CPU0213 （30 mg·kg^- 1, bid×3 d）. During the time, the changes of survival, hemodynamic parameter （mean arterial pressure： MAP, HR： heart rate）, indexes of important organs and weight of peritoneal exudates were reviewed, plasma ET-1 and serum iNOS, GSH-PX, SOD, MDA were detected, simultaneously, the activity of aorta pectoralis and was registered, the mRNA expressions of NF-κB, TNF-α, iNOS, ECE （endothelin converting enzyme）, preproET-1, ETA, ETs receptor and the activated NF-κB protein amount of mesentefic blood vessel were. detected. RESULTS： In the septic model group, the MAP and survival rate decreased （ P 〈0.01）; the HR, indexes of important organs and weight of peritoneal exudates wereincreased significantly （ P 〈 0.01 ） ; blood vessel activity of aorta pectoralis （in vivo and in vitro） were decreased; The levels of ET-1, iNOS and ROS in serum were markedly increased （ P 〈 0.01 ） ; the mRNA levels of TNF-α, iNOS, prepm ET-1, ECE, ETAR and ETBR in mesenteric blood vessel were enhanced significantly （ P 〈 0.01） ; the protein amount of activated NF-κB was increased （P 〈 0.01） versus sham-operated group. All of these changes were reversed after CPU0213 administration. CONCLUSION： CPU0213 can lessen the impairment of vascular smooth muscle cell, decrease effusion, recover vascular normal activity, degrade indexes of organs, and elevate survival rate by suppressing the ET system and NF-κB pathway.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2006年第2期145-152,共8页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
国家自然科学基金重点项目(№30230170)
国家自然科学基金项目(№30171078)
