钙敏感性受体抑制剂Calhex231对创伤失血性休克大鼠的保护作用  

Protective effect of calcium-sensing receptor inhibitor Calhex231 on traumatic hemorrhagic shock rats

作　　者：彭小勇[1] 周海军 李涛[1] 刘良明[1] 杨光明[1] Peng Xiaoyong;Zhou Haijun;Li Tao;Liu Liangming;Yang Guangming.(State Key Laboratory of Trauma, Burns and Combined Injury, Department 2, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing 400042, Chin)

机构地区：[1]陆军军医大学大坪医院野战外科研究所第二研究室,创伤、烧伤与复合伤国家重点实验室,重庆400042

出　　处：《中华创伤杂志》2018年第6期555-561,共7页Chinese Journal of Trauma

基　　金：国家自然科学基金（81571886）;军队“十三五”重大项目（AWS16J032）;教育部留学回国人员科研启动基金（2014）

摘　　要：目的探讨钙敏感性受体（CaSR）抑制剂Calhex231对创伤失血性休克大鼠的保护作用。方法144只大鼠按随机数字表法分为6组：正常组、休克组、乳酸林格液（LR）复苏组、LR＋Calhex2310．1，1，5mg／kg复苏组，用于大鼠存活情况（每组16只）和血流动力学检测（每组8只）。64只大鼠也按随机数字表法分为4组：正常组、休克组、LR复苏组、LR＋Calhex2311mg／kg复苏组，一半用于器官血流量和肠系膜上动脉血管反应性检测（每组8只），另一半用于检测肠系膜微动脉血管反应性（每组8只）。建立创伤失血性休克大鼠模型后，休克组不复苏，LR复苏组输入2倍失血量的LR，LR＋Calhex231各组先给予1倍失血量的LR输注，然后把Calhex231加入另外1倍失血量的LR中输注。从复苏开始观察24h存活情况，输液结束后立即结扎缝合；于休克前、休克末、复苏后1，2h检测血流动力学指标[平均动脉压（MAP）、左室收缩压（LVSP）、左室压力最大上升／下降速度（±ap／dtmax）]；复苏后2h检测重要器官（肝、肾）血流量及血管反应性。结果休克组在模型完成后9h内全部死亡，LR复苏组的存活情况与休克组比较稍有改善（P〉0．05），LR＋Calhex2311mg／kg、5mg／kg复苏组24h存活率和存活时间明显高于LR复苏组（P〈0．05）。LR＋Calhex231各复苏组的血流动力学指标均高于LR复苏组，其中LR＋Calhex2311mg／kg复苏组的效果最为明显（P〈0．01），MAP、LVSP、±ap／dtmax分别恢复到正常水平的64．9％、82．4％、89．8％、77．8％；同时，LR＋Calherd2311mg／kg复苏组器官（肝、肾）血流量明显增加（P〈0．01），肝脏和肾脏的血流量分别从休克的57．2％、41．0％升高到108．7％、95．1％；LR＋Calhex2311mg／kg复苏组肠系膜上动脉及其微动脉血管的收缩反应性也明显提高（P〈0．01）。结论对于创伤失血性休克大鼠，钙敏�Objective To observe the protective effects of calcium-sensing receptor （CaSR） inhibitor Calhex231 on traumatic hemorrhagic shock rats. Methods 144 SD rats were divided into six groups by random number table method： normal group, shock group, lactated Ringer＇s solution （LR） group, LR ＋ Calhex231 0.1 mg/kg group, LR ＋ Calhex231 1 mg/kg group, and LR ＋ Calhex231 5 mg/kg group, with 16 rats in each group for survival observation and 8 rats for hemodynamics test. 64 SD rats were divided into four groups： normal group, shock group, lactated Ringer＇s solution （LR） group, LR ＋ Calhex231 1 mg/kg group, with 8 rats in each group for detecting organ blood flow and superior mesenteric artery vascular reactivity and the other 8 rats for mesenteric artery vascular reactivity. After the establishment of traumatic hemorrhagic shock model, the shock group did not receive resuscitation, and the LR group was resuscitated with LR equal to two times of the blood loss volume. The three LR ＋ Calhex231 groups with different dosages were firstly given LR of equal volume to that of blood loss, and then the Calhex231 was dissolved into LR （ equal to the blood loss volume） to resuscitate. The wound was ligated and sutured immediately after resuscitation. The effect of Calhex231 on animal＇s 24- hour survival since the beginning of resuscitation was observed. The hemodynamics including the mean arterial blood pressure （ MAP）, left intraventricular systolic pressure （ LVSP）, maximal rising, and declining rate of left intraventricular pressure （ ± dp/dtmax） were observed before shock, at the end of shock, 1 hour after resuscitation, and 2 hours after resuscitation. The effects of Calhex231 on vital organ blood flow and vascular reactivity were observed 2 hours after resuscitation. Results All the shock rats died within 9 hours after the shock model was established. The survival outcomes of LR group rats were slightly improved compared with the shock group rats（ P 〈 0.05 ） . The survival ti

关 键 词：受体 钙敏感 休克 出血性 Calhex231 

分 类 号：R605.971[医药卫生—急诊医学]