4-苯基丁酸对创伤失血性休克大鼠的保护作用及与改善血管功能的关系

4-phenylbutyrate protects rats against traumatic hemorrhagic shock by improving vascular function

目的 探讨4-苯基丁酸（4-phenylbutyrate,PBA）对创伤失血性休克大鼠的保护作用及对血管反应性的影响。方法 SD大鼠192只（雌雄各半,12~14周龄,体质量180~220 g）,分为正常对照组,休克对照组,乳酸林格氏液（LR）组,PBA 5、20、50 mg/kg组,复制大鼠创伤失血性休克模型,观察不同剂量PBA对休克大鼠存活情况、血流动力学、血气指标及血管反应性的影响。结果 PBA能够改善创伤失血性休克大鼠的存活情况,使休克动物的24 h存活率从休克组的0、LR组的19%提高至PBA 20 mg/kg组的75%,动物存活时间从休克组的3.2 h、LR组的10.8 h延长至PBA 20 mg/kg组的19.9 h。PBA 20 mg/kg输注后血流动力学指标和血气指标明显优于单用LR复苏（P〈0.05,P〈0.01）。同时,PBA输注后血管收缩和舒张功能也明显升高,血管收缩反应性和舒张反应性从LR组的63.3%、73.3%分别恢复至PBA 20 mg/kg组的80.2%、93.1%（P〈0.01）。结论 PBA能改善休克后血管功能,稳定血流动力学,发挥对创伤失血性休克大鼠的保护作用。

Objective To determine the protective effects of 4-phenylbutyrate （PBA） on traumatic hemorrhagic shock and on vascular reactivity in rats. Methods One hundred and ninety-two SD rats （male and female in half, 12 to 14 weeks old, weighing 180 to 220 g） were randomly divided into 6 groups, including sham-operation group, shock control group, lactated Ringer＇ s solution （LR） group, and 5, 20 and 50 mg/kg PBA intervention groups （PBA at corresponding doses was added in LR solution）. After the establishment of traumatic hemorrhagic shock rats, the effects of PBA on the animal survival, hemodynamics, blood gases and vascular reactivity were observed and compared. Results PBA improved survival outcomes of traumatic hemorrhagic shock rats, with the 24-h survival rate increased from 0 in the shock group and 19% in the LR group to 75% in PBA 20 mg/kg intervention group, and the survival time of shock rats increased to 19.9 h in PBA 20 mg/kg group from 3.2 h in shock group and 10.8 h in LR group. Administration of PBA 20 mg/kg made the parameters of hemodynamics and blood gases better than those alone with LR resuscitation （P 〈 0.05 to 0.01 ）. And PBA also markedly increased the vascular constriction and relaxation after shock, by the constriction and vasodilator reactivity increasing to 80.2% and 93.1% in PBA 20 mg/kg group from 63.3% and 73.3% in LR group, respectively （ P 〈 0.01 ）. Conclusion PBA improves the vascular function, stabilize hemodynamics, and finally exerts the protective effects on traumatic hemorrhagic shock rats.