Ischemic preconditioning (IPC) is currently known as an effective protection strategy against the IRI.
Oxidative stress, inflammation, and calcium ion overload were involved with the ischemia-reperfusion injury. Ischemia-reperfusion injury (IRI) refers to the irreversible tissue damage caused by insufficient oxygen supply following tissue ischemia and subsequent restoration of blood supply. The ROS may stimulate the cell death pathways and trigger inflammation, resulting in inflammasome activation, pyroptosis, and intrinsic apoptosis. DNA damage, hypoxia, and metabolic stress can induce intrinsic apoptosis, which begins with mitochondrial outer membrane permeabilization (MOMP) and leads to the release of mitochondrial proteins into the cytosol. Multiple studies elucidated the role of the Fas/FasL system in the extrinsic epithelial apoptosis in LPS-induced ALI. The innate immune response can be activated by LPS through the activation of TLR4 receptors, leading to the transcription of MyD88-dependent genes, which encode proinflammatory cytokines including inactive proforms of IL-1 β and inflammasome components. The LPS has been reported to directly stimulate the activation of caspase-11, which cleaves gasdermin D (GSDMD) resulting in membrane rupture and cell lysis in rodents. Pyroptosis is triggered in response to infection. It has been elucidated that several different forms of programmed cell death (PCD), including autophagy, apoptosis, and pyroptosis, have been correlated with the LPS-induced ALI in rat models. The ROS can destroy the gas and blood barrier by damaging pulmonary vascular endothelial cells and alveolar epithelial cells, increasing their permeability, and causing pulmonary edema it can also upregulate the expression of inflammatory factors and induce inflammation. Alveolar macrophages (AM) activated by LPS can release cytokines such as TNF- α and IL-1 β to initiate the inflammatory cascade, producing a large number of inflammatory mediators and factors, and reactive oxygen species (ROS). The LPS can directly damage the alveolar-capillary barrier, lung epithelial cells, and pulmonary vascular endothelial cells. Lipopolysaccharide (LPS), the endotoxin derived from the outer membrane of Gram-negative bacteria, which is believed to be one of the most frequent triggers of sepsis, is a powerful causative agent of systemic inflammation. At present, the treatment for ALI/ARDS is mainly supportive, and novel therapeutic strategies are urgently needed.
Uncontrolled inflammation is the main cause of death, with a mortality rate of over 30%. It often progresses to acute respiratory distress syndrome (ARDS) and requires mechanical ventilation. The ALI is characterized by hypoxemia, lung gas and blood barrier damage, bilateral pulmonary inflammatory infiltration, and noncardiogenic interstitial edema. IntroductionĪcute lung injury (ALI) is a life-threatening parenchymal lung disease caused by various pathogenic factors. RInPC could inhibit inflammation and attenuate oxidative stress, thereby reducing intrinsic apoptosis and providing lung protection in the LPS-induced ALI in rats. Increasing of TNF- α, IL-1 β, and IL-6 induced by the LPS was inhibited, while IL-10 was significantly increased by RInPC, compared to the LPS group. Reduction of MPO and MDA and increasing of SOD activity were found significantly improved by the RInPC. Apoptotic cells were reduced significantly by the RInPC, with the simultaneous improvement of apoptosis-related proteins. In the present study, we demonstrated that the RInPC significantly attenuated the LPS-induced ALI in rats. Supplementary experiments in the LPS and RInPC groups were conducted to ensure that 6 animals in each group reached the end of the experiment. There were 2 rats in the LPS group and 1 in the RInPC group who died before the end of the experiment. The RInPC was performed prior to the LPS injection via tourniquet blockage of blood flow to the right hind limb and adopted three cycles of 5 min tying followed by 5 min untying. Eighteen rats were equally and randomly divided into the control (NS injection), LPS (LPS injection), and RInPC groups. A total of 21 Sprague-Dawley rats were used for the animal experiments. As inflammation and oxidative stress are the common pathological basis of endotoxin-induced inflammatory injury and ischemic reperfusion injury (IRI), we speculate that remote ischemic preconditioning (RIPC) can be protective for ALI when used as remote inflammatory preconditioning (RInPC). Acute lung injury (ALI) always leads to severe inflammation.