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丙酮酸直接腹腔复苏对大鼠失血性休克所致肠道损伤的保护作用。

Protection against intestinal injury from hemorrhagic shock by direct peritoneal resuscitation with pyruvate in rats.

作者信息

Zhang Jing-Jing, Zhang Zong-Ze, Ke Jian-Juan, He Xiang-Hu, Zhan Jia, Chen Dong-Ling, Wang Yi-Peng, Wang Yan-Lin

机构信息

Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.

出版信息

Shock. 2014 Nov;42(5):464-71. doi: 10.1097/SHK.0000000000000230.

Abstract

OBJECTIVE

We explored the effects of direct peritoneal resuscitation with pyruvate-peritoneal dialysis solution (PDS) following intravenous resuscitation (VR) on intestinal ischemia-reperfusion injury in rats with hemorrhagic shock (HS).

METHODS

Fifty rats were randomly assigned equally to five groups. In group sham, a surgical operation was performed on rats without shock or resuscitation. In group VR, rats were subjected only to VR. In groups NS, LA, and PY, direct peritoneal resuscitation was performed with normal saline (NS), lactate-based PDS (Lac-PDS), and pyruvate-based PDS (Pyr-PDS), respectively, after VR. Mean arterial pressure was monitored in the right common carotid artery. Two hours after resuscitation, the lactate level in arterial blood and the wet weight/dry weight ratio of the intestine were determined. The intestinal mucosal damage index was estimated, and ultrastructural changes in the intestinal mucosa were observed. Malondialdehyde, myeloperoxidase, nitric oxide, and tumor necrosis factor α levels were also measured.

RESULTS

Two hours after HS and resuscitation, the increase in arterial blood lactate and intestinal wet weight/dry weight ratio declined significantly in rats from Groups LA and PY compared with groups VR and NS, whereas group PY was more advantageous in the changes of these parameters. The intestinal mucosal damage index and ultrastructural changes were also improved in groups LA and PY when compared with groups VR and NS. Protection was more apparent with Pyr-PDS than Lac-PDS. Hemorrhagic shock resulted in a significant increase in malondialdehyde levels and myeloperoxidase activity and was accompanied by overexpression of tumor necrosis factor α and a reduction in nitric oxide levels. These changes were significantly attenuated by Lac-PDS and Pyr-PDS at 2 h after resuscitation, and Pyr-PDS showed more effective protection for the intestine than Lac-PDS.

CONCLUSIONS

Direct peritoneal resuscitation with Lac-PDS and Pyr-PDS after VR alleviated intestinal injury from HS in rats, and Pyr-PDS was superior to Lac-PDS in its protective effect. Mechanisms of action might include the elimination of free oxygen radicals, reduction of neutrophil infiltration, inhibition of the inflammatory response, and regulation of intestinal mucosal blood flow and barrier function.

摘要

目的

我们探讨了静脉复苏(VR)后用丙酮酸腹膜透析液(PDS)进行直接腹膜复苏对失血性休克(HS)大鼠肠缺血再灌注损伤的影响。

方法

将50只大鼠随机均分为五组。假手术组大鼠仅接受手术操作,不进行休克或复苏。VR组大鼠仅接受VR。NS组、LA组和PY组在VR后分别用生理盐水(NS)、乳酸盐腹膜透析液(Lac-PDS)和丙酮酸盐腹膜透析液(Pyr-PDS)进行直接腹膜复苏。通过右颈总动脉监测平均动脉压。复苏后2小时,测定动脉血乳酸水平和肠组织湿重/干重比。评估肠黏膜损伤指数,并观察肠黏膜的超微结构变化。同时检测丙二醛、髓过氧化物酶、一氧化氮和肿瘤坏死因子α水平。

结果

HS和复苏后2小时,与VR组和NS组相比,LA组和PY组大鼠动脉血乳酸升高及肠组织湿重/干重比下降明显减轻,而PY组在这些参数变化方面更具优势。与VR组和NS组相比,LA组和PY组的肠黏膜损伤指数及超微结构变化也有所改善。Pyr-PDS的保护作用比Lac-PDS更明显。失血性休克导致丙二醛水平和髓过氧化物酶活性显著升高,并伴有肿瘤坏死因子α的过度表达和一氧化氮水平的降低。复苏后2小时,Lac-PDS和Pyr-PDS可显著减轻这些变化,且Pyr-PDS对肠道的保护作用比Lac-PDS更有效。

结论

VR后用Lac-PDS和Pyr-PDS进行直接腹膜复苏可减轻HS大鼠的肠损伤,且Pyr-PDS的保护作用优于Lac-PDS。作用机制可能包括清除自由基、减少中性粒细胞浸润、抑制炎症反应以及调节肠黏膜血流和屏障功能。

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