血压靶向阶梯复苏治疗大鼠失血性休克。

Blood pressure-targeted stepwise resuscitation for hemorrhagic shock in rats.

机构信息

From the Department of Emergency Medicine (J.H.L., K.K., Y.H.J., J.E.R., A.R.D., M.J.L., C.J.P., J.K., H.C.), Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do; and Department of Pathology (M.A.K, K.B.L.), Seoul National University Hospital, Seoul, Korea.

出版信息

J Trauma Acute Care Surg. 2014 Mar;76(3):771-8. doi: 10.1097/TA.0000000000000106.

DOI:10.1097/TA.0000000000000106

PMID:24553547

Abstract

BACKGROUND

Generation of reactive oxygen species (ROS) is an important mechanism of ischemia-reperfusion injury. Abrupt reoxygenation compared with slow reoxygenation has been known to increase ROS generation. Thus, slow and stepwise reperfusion can reduce ROS generation and subsequent ischemia-reperfusion injury. This study investigated the effect of slow reperfusion by blood pressure-targeted stepwise resuscitation (PSR) in hemorrhagic shock.

METHODS

Pressure-controlled hemorrhagic shock was induced in male Sprague-Dawley rats for 1 hour. Rats were then allocated to one of three groups (no-resuscitation group, n = 14; PSR group, n = 15; rapid normalization of blood pressure (RR) group, n = 15). Survival time and hemodynamic changes were recorded and compared. Blood samples and liver tissue were harvested after 6 hours of resuscitation in surviving rats.

RESULTS

All of the rats in the no-resuscitation group were expired before the end of the 6-hour observation period. Survival times were significantly longer in the PSR group than in the RR group (survival rates, 11 of 15 vs. 5 of 15, log rank p = 0.032). Plasma amino alanine transferase, histologic liver injury, and ROS generation in the liver tissue were significantly lower in the PSR group than in the RR group (all findings significant, p < 0.05). In addition, PSR significantly decreased plasma nitric oxide, liver interleukin 1β, and liver interleukin 6 compared with rapid resuscitation in addition to augmenting Akt survival pathways (all p < 0.05).

CONCLUSION

Slow reperfusion by PSR decreased mortality, ROS generation, and liver injury in rats undergoing hemorrhagic shock. Stepwise resuscitation also decreased inflammatory cytokine production and augmented Akt survival pathways.

摘要

背景

活性氧（ROS）的产生是缺血再灌注损伤的重要机制。与缓慢再氧合相比，突然再氧合已被证实会增加 ROS 的产生。因此，缓慢和逐步再灌注可以减少 ROS 的产生和随后的缺血再灌注损伤。本研究探讨了通过血压靶向逐步复苏（PSR）进行缓慢再灌注对失血性休克的影响。

方法

雄性 Sprague-Dawley 大鼠进行压力控制的失血性休克 1 小时。然后，将大鼠分为三组（无复苏组，n = 14；PSR 组，n = 15；快速血压正常化（RR）组，n = 15）。记录并比较生存时间和血流动力学变化。在幸存大鼠复苏 6 小时后采集血液样本和肝组织。

结果

无复苏组的所有大鼠在 6 小时观察期结束前均死亡。PSR 组的生存时间明显长于 RR 组（存活率，15 例中有 11 例 vs. 15 例中有 5 例，对数秩检验 p = 0.032）。PSR 组的血浆丙氨酸氨基转移酶、组织学肝损伤和肝组织中的 ROS 生成明显低于 RR 组（所有结果均有统计学意义，p < 0.05）。此外，PSR 与快速复苏相比，还显著降低了血浆一氧化氮、肝白细胞介素 1β 和肝白细胞介素 6，同时增加了 Akt 生存途径（所有 p < 0.05）。