丙泊酚对脓毒症大鼠血管低反应性的改善作用及机制  

Improved effect and mechanism of propofol on vascular hyporeactivity in septic rats

作　　者：孙悦 张杰 张濒丹 彭小勇 周远群 李涛 刘良明 陈力勇 SUN Yue;ZHANG Jie;ZHANG Bindan;PENG Xiaoyong;ZHOU Yuanqun;LI Tao;LIU Liangming;CHEN Liyong(Department of Anesthesiology,Army Medical Center of PLA,Chongqing,400042,China;State Key Laboratory of Trauma and Chemical Poisoning,Department of War Wound Shock and Transfusion,Army Medical Center of PLA,Chongqing,400042,China)

机构地区：[1]陆军特色医学中心麻醉科,重庆400042 [2]陆军特色医学中心战伤休克与输血研究室创伤与化学中毒全国重点实验室,重庆400042

出　　处：《陆军军医大学学报》2024年第3期232-239,共8页Journal of Army Medical University

基　　金：国家自然科学基金重点项目(81730059)。

摘　　要：目的 观察丙泊酚对脓毒症大鼠血管低反应性的改善作用及其机制。方法 96只12周龄的SD大鼠,雌雄不论,体质量200~220 g。采用随机数字表法分为假手术组(n=16)、脓毒症组(n=16)、丙泊酚组(n=16)、丙泊酚+ROCK抑制剂Y-27632组(n=16)、丙泊酚+PKCα抑制剂GO6976组(n=16)、丙泊酚+IP3抑制剂2-APB组(n=8)以及丙泊酚+细胞缝隙连接抑制剂甲氯灭酸钠(Movens)组(n=8),采用离体血管环张力测定技术和血管环钙敏感性测定技术,研究丙泊酚对脓毒症大鼠血管低反应性的改善作用及其与RhoA/ROCK、PKCα、IP3和细胞缝隙连接的关系。结果 离体血管环反应性测定实验和钙敏感性测定实验表明,与假手术组相比,脓毒症组大鼠血管对去甲肾上腺素的收缩反应性和钙敏感性均显著降低,量-效曲线右移,其中肠系膜上动脉降低最为明显,降低比例达51.42%(P<0.05);而丙泊酚组可明显改善脓毒症组血管低反应性以及钙敏感性,在股动脉的恢复作用最为显著,恢复比例达89.57%(P<0.05)。钙敏感性测定实验结果表明,与丙泊酚组相比,丙泊酚+Y-27632组和丙泊酚+GO6976组量-效曲线右移,Y-27632和GO6976可显著拮抗丙泊酚对严重脓毒症大鼠肠系膜上动脉主干血管钙敏感性的改善作用,抑制率分别为146.95%和88.63%(P<0.05)。离体血管环反应性测定实验显示,丙泊酚+Y-27632组和丙泊酚+Movens组可显著拮抗丙泊酚组对脓毒症组大鼠血管低反应性的改善作用,抑制程度分别为40.79%和169.90%(P<0.05);而丙泊酚+GO6976组和丙泊酚+2-APB组无明显变化。结论 丙泊酚治疗可显著改善脓毒症大鼠血管低反应性,其机制可能是通过RhoA/ROCK通路改善血管钙敏感性。Objective To observe the improved effect of propofol on vascular hyporeactivity in septic rats and its underlying mechanism.Methods A total of 96 SD rats(12 weeks old,both genders,weighing 200~220 g) were randomly divided into sham group(n=16),sepsis group(n=16,cecal ligation and puncture),propofol group(n=16),propofol+ROCK inhibitor Y-27632 group(n=16),propofol+PKCα inhibitor GO6976 group(n=16),propofol+IP3 inhibitor 2-APB group(n=8) and propofol+gap junction inhibitor metoclopramide sodium(Movens) group(n=8).In vitro vascular ring reactivity and vascular calcium sensitivity were measured to observe the improved effects of propofol on vascular hyporeactivity in septic rats and its relationships with RhoA/ROCK,PKCα,IP3 and cell gap junction.Results Determination of in vitro vascular ring and calcium sensitivity showed that the contractile reactivity to norepinephrine(NE) and to calcium sensitivity were significantly decreased in the arterial rings isolated from the septic rats compared with those from the sham group,with the dose-response curve shifting to the right,and most significant decrease by 51.42% in the superior mesenteric artery(SMA,P<0.05).Propofol treatment significantly improved the hyporeactivity and calcium sensitivity of the vessels isolated from the septic rats,especially those of the femoral artery with a recovery rate of 89.57%(P<0.05).In comparison with the propofol group,the dose-response curves of the propofol+Y-27632 group and the propofol+GO6976 group were shifting to right,indicating that Y-27632 and GO6976 could significantly inhibit the amelioration of propofol on calcium sensitivity of SMA in severely septic rats with an inhibitory rate of 146.95% and 88.63%(P<0.05),respectively.Isolated vascular reactivity measurement demonstrated that Y-27632 and Movens treatment significantly antagonized the ameliorated role of propofol on hyporeactivity of blood vessels from the septic rats with an inhibitory rate of 40.79% and 169.90%(P<0.05),separately,while no such effect was observed in the p

关 键 词：脓毒症 丙泊酚 血管低反应性 RhoA/ROCK 钙敏感性 

分 类 号：R322.12[医药卫生—人体解剖和组织胚胎学] R631.1[医药卫生—基础医学] R971.3