A Dual Protective Effect of Intestinal Remote Ischemic Conditioning in a Rat Model of Total Hepatic Ischemia
A Dual Protective Effect of Intestinal Remote Ischemic Conditioning in a Rat Model of Total Hepatic Ischemia
复制标题
DOI：
10.3390/jcm8101546
复制
发表时间：
2019-10-01
影响因子：
3.9
通讯作者：
Tolba, Rene H.
中科院分区：
文献类型：
--
作者：
Czigany, Zoltan;Hata, Koichiro;Tolba, Rene H.
本研究旨在探讨肠远端缺血预处理（iRIC）对大鼠全肝缺血（THI）模型缺血再灌注损伤（IRI）和肠屏障完整性的影响。雄性Wistar大鼠50只，250 ~ 300 g，随机分为RIC/Control两组。采用夹紧肝十二指肠韧带诱导THI 30分钟。应用iRIC进行4分钟缺血，然后通过夹紧肠系膜上动脉进行11分钟再灌注。动物于再灌注后1、2、6、24 h处死（n = 5/组/时间点）。肠道RIC显著改善了回肠和肝脏的微循环。肝脏：1.34 +/- 0.12 vs. 0.97 +/- 0.20 mu mol/g, p = 0.04)，肝细胞损伤明显减轻（ALT: 2409 +/- 447 vs. 6613 +/- 1117 IU/L, p = 0.003）。全身和门静脉IL-6和tnf - α水平在iRIC后明显降低，表明炎症反应减少。iRIC导致肠道屏障在结构和功能上的保存。这些结果表明，iRIC可能通过减少IRI和全身炎症反应，同时通过减轻严重肠道充血和细菌易位的严重后果，对大鼠的THI有害影响提供有效的保护。
The present study aimed to investigate the effects of intestinal remote ischemic preconditioning (iRIC) on ischemia-reperfusion injury (IRI) and gut barrier integrity in a rat model of total hepatic ischemia (THI). Male Wistar rats (n = 50; 250-300 g) were randomly allocated into two experimental groups: RIC/Control. Thirty minutes of THI was induced by clamping the hepatoduodenal ligament. iRIC was applied as 4-min of ischemia followed by 11-min of reperfusion by clamping the superior mesenteric artery. Animals were sacrificed at 1, 2, 6, 24 h post-reperfusion (n = 5/group/timepoint). RIC of the gut significantly improved microcirculation of the ileum and the liver. Tissue ATP-levels were higher following iRIC (Liver: 1.34 +/- 0.12 vs. 0.97 +/- 0.20 mu mol/g, p = 0.04) and hepatocellular injury was reduced significantly (ALT: 2409 +/- 447 vs. 6613 +/- 1117 IU/L, p = 0.003). Systemic- and portal venous IL-6 and TNF-alpha levels were markedly lower following iRIC, demonstrating a reduced inflammatory response. iRIC led to a structural and functional preservation of the intestinal barrier. These results suggest that iRIC might confer a potent protection against the detrimental effects of THI in rats via reducing IRI and systemic inflammatory responses and at the same time by mitigating the dramatic consequences of severe intestinal congestion and bacterial translocation.