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治疗性轻度低体温可改善严重脓毒症大鼠的早期预后。

Therapeutic mild hypothermia improves early outcomes in rats subjected to severe sepsis.

机构信息

Department of Emergency Medicine, Second Hospital of Zhejiang University School of Medicine and Research Institute of Emergency Medicine, Zhejiang University. No. 88 Jiefang Road, Hangzhou, Zhejiang, China.

Department of Burns, Second Hospital of Zhejiang University School of Medicine. No. 88 Jiefang Road, Hangzhou, Zhejiang, China.

出版信息

Life Sci. 2018 Apr 15;199:1-9. doi: 10.1016/j.lfs.2018.03.002. Epub 2018 Mar 2.

Abstract

AIMS

Therapeutic hypothermia has shown beneficial effects in sepsis. This study focused on its mechanism.

MAIN METHODS

Sixteen male Sprague-Dawley rats underwent cecal ligation and perforation and subsequently were treated with either hypothermia (HT; body temperature cooled and maintained at 34 °C by ice pad for 10 h; n = 8) or normothermia (NT; n = 8). Three additional rats underwent sham surgery. The body temperatures of the sham-operated and NT groups were maintained at 38 °C with a thermal pad. After the hypothermia treatment, the HT rats were rewarmed for 2 h. The groups were compared for circulating cytokines (IL-6, IL-10), lactate, high mobility group box-1 protein (HMGB1), and lung and intestinal lesions. Animals were observed for 24 h.

KEY FINDINGS

Compared with the sham-operated group, the 2 sepsis group rats had significantly higher circulating IL-6, HMGB1, and lactate levels, and tissue injury. In the HT rats, the levels of IL-6, HMGB1, and lactate, the lung wet-to-dry ratio, and lung and intestinal damage were significantly lower than that of the NT group. Circulating IL-10 levels increased significantly after 12 h in the sepsis groups compared with sham animals, while that of the NT and HT groups were comparable. The survival rates of the NT and HT rats were also comparable.

SIGNIFICANCE

Therapeutic hypothermia in a rat model of sepsis was associated with lower levels of circulating IL-6 and HMGB1, and less capillary leakage and tissue edema. These results suggest that mild hypothermia has potential as a therapy in sepsis.

摘要

目的

亚低温治疗在脓毒症中显示出有益的效果。本研究聚焦于其作用机制。

主要方法

16 只雄性 Sprague-Dawley 大鼠接受盲肠结扎穿孔术,随后分别接受亚低温(HT;通过冰垫将体温冷却并维持在 34°C 10 小时;n=8)或正常体温(NT;n=8)治疗。另外 3 只大鼠接受假手术。假手术和 NT 组的大鼠体温通过热垫维持在 38°C。亚低温治疗后,HT 大鼠进行 2 小时复温。比较各组循环细胞因子(IL-6、IL-10)、乳酸、高迁移率族蛋白 B1(HMGB1)以及肺和肠损伤情况。动物观察 24 小时。

主要发现

与假手术组相比,2 个脓毒症组大鼠的循环 IL-6、HMGB1 和乳酸水平以及组织损伤显著更高。在 HT 大鼠中,IL-6、HMGB1 和乳酸水平、肺湿重/干重比以及肺和肠损伤均显著低于 NT 组。与假动物相比,脓毒症组大鼠在 12 小时后循环 IL-10 水平显著升高,而 NT 和 HT 组之间没有差异。NT 和 HT 大鼠的存活率也相当。

意义

在脓毒症大鼠模型中,亚低温治疗与较低的循环 IL-6 和 HMGB1 水平以及更少的毛细血管渗漏和组织水肿有关。这些结果表明,轻度亚低温可能成为脓毒症的一种治疗方法。

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