中文摘要：

目的：通过非选择性内皮素受体拮抗剂CPU20213对结扎小鼠和大鼠盲肠并穿孔致感染性休克血管活性的改善,探讨其通过干预内皮素-活性氧（ET-ROS）轴心治疗感染性休克可能的作用机制.方法：结扎小鼠盲肠并穿孔,8 h后按30 mg·kg-1皮下注射（sc）CPU0213,bid×3 d.观察术后该时间段的存活率,计算腹腔渗出液重量,生命器官脏器系数,心肌、肾匀浆和血清丙二醛（MDA）,谷胱甘肽过氧化物酶（GSH-PX）含量及胸主动脉血管活性;同样方法结扎大鼠盲肠,检测血浆ET-1浓度和肠系膜血管ETA和ETB受体mRNA表达.结果：模型组小鼠存活率明显降低,生命器官脏器系数明显增加,腹腔渗出液显著增多,GSH-PX活性下降,MDA含量增加,血管收缩和舒张功能及NO生物利用度明显降低;大鼠血浆ET-1浓度显著升高,肠系膜血管ETA和ETB受体mRNA表达上调;CPU20213治疗后,均有不同程度改善.结论：CPU0213通过阻断ET-ROS轴心,改善血管活性,减少腹腔渗出液,提高存活率.

英文摘要：

Objective：To assess the amelioration of a non-selective endothelin （ETA/ETB ） receptor antagonist CPU0213 on vascular activity of septic shock mice/rats induced by cecal ligation and puncture （CLP） , and explore its possible mechanism. Methods：In 8 hours after the CLP, mice were subcutaneously administered with CPU0213 （30 rag·kg^-1） twice daily for 3 days. The survival rate, peritoneal exudates, indexes of important organs in the 3-day course post the CLP were monitored; MDA and GSH-PX levels in serum, heart and kidney were detected, and the activity of aorta peetoralis were measured. Rats that underwent the same CLP procedure were studied in the plasma endothelin-1 levels and mRNA expression of ETA, ETs receptors of mesenteric blood vessel. Results：The survival rate and vascular activity （ vascular tension, relaxation and NO bioavailability） of thoracic aorta were significantly decreased, the weight indexes of vital organs and the weight of peritoneal exudates were remarkably increased, and also the abnormal levels of MDA and GSH-PX appeared in mice of model group. The ET-1 levels and mRNA expression of ETA, ETB receptors of mesenterie blood vessel were markedly increased in rats of model group. All of those were reversed significantly after treatment with CPU0213. Conclusion： CPU0213 lessehed the impaired vascular activity, abdominal effusion, and in- creased survival rate by intervening ET-l-reactive oxygen species pathway.