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拉扎罗类化合物U - 74500A对犬小肠热缺血及再灌注损伤的作用

Lazaroid U-74500A for warm ischemia and reperfusion injury of the canine small intestine.

作者信息

Tanaka H, Zhu Y, Zhang S, Ishizaki N, Jin M B, Azuma T, Lee R, Starzl T E, Todo S

机构信息

Pittsburgh Transplantation Institute, University of Pittsburgh, Pa, USA.

出版信息

J Am Coll Surg. 1997 Apr;184(4):389-96.

PMID:9100685
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2677968/
Abstract

BACKGROUND

Although lazaroids have been shown to protect various organs from ischemia/reperfusion injury, results obtained in the small intestine have been conflicting.

STUDY DESIGN

The canine small intestine was made totally ischemic for 2 hours by occluding the superior mesenteric artery and the superior mesenteric vein with interruption of the mesenteric collateral vessels. A lazaroid compound, U74500A, or a citrate vehicle was given intravenously to each of the six animals for 30 minutes before intestinal ischemia. Intestinal tissue blood flow, lipid peroxidation, neutrophil infiltration, adenine nucleotides and their catabolites, and histologic changes after reperfusion were determined.

RESULTS

Lazaroid treatment attenuated decline of the mucosal and serosal blood flow after reperfusion. Accumulation of lipid peroxidation products and neutrophils in mucosal tissues was markedly inhibited by the treatment. Postischemic energy resynthesis was also augmented by lazaroid. Morphologically, mucosal architectures were better preserved with lazaroid treatment after reperfusion, and recovered to normal by postoperative day 3 in the treated group and by postoperative day 7 in control animals.

CONCLUSIONS

Lazaroids protect the canine small intestine from ischemia/reperfusion injury by inhibiting lipid peroxidation and neutrophil infiltration. Dogs are tolerant of 2-hour normothermic complete intestinal ischemia.

摘要

背景

尽管已证明拉扎oids可保护各种器官免受缺血/再灌注损伤,但在小肠中获得的结果却相互矛盾。

研究设计

通过阻断肠系膜上动脉和肠系膜上静脉并中断肠系膜侧支血管,使犬小肠完全缺血2小时。在肠道缺血前30分钟,给六只动物中的每只静脉注射一种拉扎oid化合物U74500A或柠檬酸盐载体。测定再灌注后的肠道组织血流量、脂质过氧化、中性粒细胞浸润、腺嘌呤核苷酸及其分解代谢产物以及组织学变化。

结果

拉扎oid治疗减轻了再灌注后粘膜和浆膜血流量的下降。该治疗明显抑制了粘膜组织中脂质过氧化产物和中性粒细胞的积累。拉扎oid还增强了缺血后能量的重新合成。形态学上,再灌注后拉扎oid治疗能更好地保存粘膜结构,治疗组术后第3天恢复正常,对照组动物术后第7天恢复正常。

结论

拉扎oids通过抑制脂质过氧化和中性粒细胞浸润,保护犬小肠免受缺血/再灌注损伤。犬能耐受2小时的常温完全性肠道缺血。

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本文引用的文献

1
The physiological response of the small bowel of the dog to ischemia including prolonged in vitro preservation of the bowel with successful replacement and survival.狗小肠对缺血的生理反应,包括肠道长时间体外保存并成功置换和存活。
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Comparison of various lazaroid compounds for protection against ischemic liver injury.用于预防缺血性肝损伤的各种拉扎罗类化合物的比较。
Transplantation. 1997 Jan 27;63(2):202-8. doi: 10.1097/00007890-199701270-00005.
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Protective effect of the lazaroid U74006F in cold ischemia-reperfusion injury of the liver.拉扎罗类药物U74006F对肝脏冷缺血-再灌注损伤的保护作用。
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Mechanisms and effects of lipid peroxidation.脂质过氧化的机制与影响
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Oxygen free radical induced damage during intestinal ischemia/reperfusion in normal and xanthine oxidase deficient rats.正常大鼠和黄嘌呤氧化酶缺陷大鼠肠道缺血/再灌注期间氧自由基诱导的损伤
Mol Cell Biochem. 1993 Jul 7;124(1):59-66. doi: 10.1007/BF01096382.
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Inhibition of intestinal lipid peroxidation does not minimize morphologic damage.抑制肠道脂质过氧化并不能使形态学损伤最小化。
J Surg Res. 1993 Nov;55(5):553-8. doi: 10.1006/jsre.1993.1183.