Department of Anesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 21, 24105, Kiel, Germany.
Department of Cardiovascular Surgery, University Hospital of Schleswig-Holstein, Kiel, Germany.
J Transl Med. 2019 Apr 29;17(1):136. doi: 10.1186/s12967-019-1885-4.
Remote ischemic preconditioning (RIPC) is a phenomenon, whereby repeated, non-lethal episodes of ischemia to an organ or limb exert protection against ischemia-reperfusion (I/R) injury in distant organs. Despite intensive research, there is still an apparent lack of knowledge concerning the RIPC-mediated mechanisms, especially in the intestine. Aim of this study was to evaluate possible protective effects RIPC on intestinal I/R injury.
Thirty rats were randomly assigned to four groups: I/R; I/R + RIPC; Sham; Sham + RIPC. Animals were anesthetized and the superior mesenteric artery was clamped for 30 min, followed by 60 min of reperfusion. RIPC-treated rats received 3 × 5 min of bilateral hindlimb I/R prior to surgery, sham groups obtained laparotomy without clamping. After I/R injury serum/tissue was analyzed for: Mucosal damage, Caspase-3/7 activity, expression of cell stress proteins, hydrogen peroxide (HO) and malondialdehyde (MDA) production, Hypoxia-inducible factor-1α (HIF-1α) protein expression and matrix metalloproteinase (MMP) activity.
Intestinal I/R resulted in increased mucosal injury (P < 0.001) and elevated Caspase-3/7 activity (P < 0.001). RIPC significantly reduced the histological signs of intestinal I/R injury (P < 0.01), but did not affect Caspase-3/7 activity. Proteome profiling suggested a RIPC-mediated regulation of several cell stress proteins after I/R injury: Cytochrome C (+ 157%); Cited-2 (- 39%), ADAMTS1 (+ 74%). Serum concentrations of HO and MDA remained unchanged after RIPC, while the reduced intestinal injury was associated with increased HIF-1α levels. Measurements of MMP activities in serum and intestinal tissue revealed an attenuated gelatinase activity at 130 kDa within the serum samples (P < 0.001) after RIPC, while the activity of MMPs within the intestinal tissue was not affected by I/R injury or RIPC.
RIPC ameliorates intestinal I/R injury in rats. The underlying mechanisms may involve HIF-1α protein expression and a decreased serum activity of a 130 kDa factor with gelatinase activity.
远程缺血预处理（RIPC）是一种现象，即器官或肢体的反复非致死性缺血事件对远处器官的缺血再灌注（I/R）损伤发挥保护作用。尽管进行了深入的研究，但对于 RIPC 介导的机制，尤其是在肠道中，仍然明显缺乏了解。本研究旨在评估 RIPC 对肠道 I/R 损伤的可能保护作用。
30 只大鼠随机分为 4 组：I/R；I/R+RIPC；假手术；假手术+RIPC。动物麻醉后夹闭肠系膜上动脉 30 分钟，再灌注 60 分钟。RIPC 处理的大鼠在手术前接受 3×5 分钟的双侧后肢 I/R，假手术组仅进行剖腹术而不夹闭。I/R 损伤后，分析血清/组织中的以下指标：黏膜损伤、Caspase-3/7 活性、细胞应激蛋白表达、过氧化氢（HO）和丙二醛（MDA）生成、缺氧诱导因子-1α（HIF-1α）蛋白表达和基质金属蛋白酶（MMP）活性。
肠道 I/R 导致黏膜损伤增加（P<0.001）和 Caspase-3/7 活性升高（P<0.001）。RIPC 显著减轻肠道 I/R 损伤的组织学征象（P<0.01），但不影响 Caspase-3/7 活性。蛋白质组学分析表明，RIPC 介导了 I/R 损伤后几种细胞应激蛋白的调节：细胞色素 C（+157%）；Cited-2（-39%），ADAMTS1（+74%）。RIPC 后血清中 HO 和 MDA 浓度保持不变，而减轻的肠道损伤与 HIF-1α 水平升高有关。血清和肠道组织中 MMP 活性的测量显示，RIPC 后血清样本中 130 kDa 明胶酶活性降低（P<0.001），而 I/R 损伤或 RIPC 对肠道组织中 MMP 活性没有影响。
RIPC 可改善大鼠肠道 I/R 损伤。潜在机制可能涉及 HIF-1α 蛋白表达和血清中 130 kDa 明胶酶活性降低的因子。
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