![]() Įxperimental groups and sample collection Six cycles of 4 min of limb ischemia followed by 4 min of reperfusion were subsequently performed. The femoral vascular bundle (femoral artery and vein) was isolated from the surrounding muscles and clamped with a vascular microclamp. įor RIPC, a longitudinal skin incision was performed from the umbilical midline level to the right knee. Louis, MO) at 16 h and 3 h preoperation, as described previously. To inhibit the activity of HO-1, mice were treated with Zinc protoporphyrin (Znpp, 10 µmol/kg, Sigma-Aldrich, St. Sham controls only received 4 ml/kg of 0.9% NaCl and the operation but no vascular occlusion. ![]() Reperfusion was initiated by removal of the clamp. The blood supply for the median and lateral left lobes were interrupted by a vascular microclamp for 45 min. Briefly, mice were anesthetized with sodium chloralic hydras (30 mg/kg, intraperitoneal), and a midline incision was performed. Warm liver IRI was carried out as described by Shan Zeng et al. Given this, we hypothesized that autophagy is regulated by HO-1, which is induced by RIPC to protect the liver from IR injury. Additionally, HO-1 has been recognized as a protein that is essential to limiting inflammation and preventing cell death or apoptosis, however the mechanisms, including a link to autophagy, are not well defined. Autophagy is an adaptive response in liver IR models to limit cellular death and organ damage. Furthermore, it may yield a novel strategy to ameliorate the effects of liver IR via inducing autophagy. A study showed that decreased autophagic levels may lead to the increased sensitivity of aged livers to IRI both in vitro and in vivo. Growing evidence has revealed that autophagy plays a protective role in liver IRI, partly by consuming damaged and dysfunctional mitochondria to prevent the release of cytochrome C and mitochondrial death signaling, and potentially contributes to the regulation of oxygen consumption. It is primarily categorized as a process incited by nutrient starvation. However, the molecular mechanism of the protective role of HO-1 induced by RIPC remains unclear.Īutophagy (Greek for “self-eating”) is a general term for processes in which cytoplasmic materials, including organelles, are wrapped up by a double membrane vesicle, termed an autophagosome, for degradation. Our previous work revealed that RIPC may induce HO-1 to protect the liver from IRI in a small-for-size liver transplantation model. Studies have shown that overexpression of HO-1 induced by transient limb ischemia may play a protective role in hepatic IRI in rats. Pharmacologic-induced upregulation of HO-1 is protective of cells and organs, whereas HO-1 inhibition may abolish the effect and aggravate the damage –. Overexpression of HO-1 may protect the liver from IRI via anti-inflammatory and anti-apoptotic effects. The heme oxygenase (HO) system is part of a vital cell-signaling pathway that occurs in response to cellular injury or stress. RIPC involves brief periods of ischemia followed by reperfusion of one organ or tissue that subsequently affords protection to a remote organ or tissue suffering from a prolonged ischemic injury. ![]() This proved to be a novel and simple way to protect the liver without direct stress. The first work on remote ischemic preconditioning (RIPC), described by Przyklenk, et al in 1993, showed that brief occlusion of the circumflex artery protects myocardium from subsequent continuous IRI. Surgical, pharmacologic strategies, and gene therapy are the major methods used to alleviated liver IRI. This remains an important clinical problem during shock, hepatic resection, and liver transplantation. Liver ischemia/reperfusion (IR) injury (IRI) is a phenomenon in which cellular damage caused by hypoxia is accentuated following return of blood flow and restoration of oxygen delivery.
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