| Background:The intestinal ischemia reperfusion (II/R) injury is a life-threatening clinical surgical emergency. II/R produces many systemic effects, which are even more severe than local damage in the intestine itself. How to protect the intestine and remote organs from ischemia reperfusion injury has become a hot spot in multidisciplinary studies. Studies have shown that II/R induced remote organ injury is a clinical problem with diverse causes such as intestinal barrier damage, bacteria translocation and oxidative stress and activation of multiple inflammatory mediators. Ginsenoside Rbl is a major active constitutent of ginseng. It has been demonstrated that ginsenoside Rbl has the anti-oxidative effect and therefore can protect multiple organs from ischemia reperfusion injury. But it has not fully elucidated whether it can also attenuate II/R induced acute lung injury. Nrf2/HO-l signaling pathway has been found as the most important endogenous anti-oxidative stress mechanism so far. It has been reported that Nrf2/HO-l signaling pathway performs a fundamental role in protecting the body against the xenobiotics and oxidative injury in the pathophysiology of digestive system, circulation system, nervous system and immune system diseases. However, there still remain many doubts as to the pathophysiology and therapeutics of II/R induced remote organ dysfunction, revealing the need for new research to obtain a more complete understanding of organ protection mechanisms of ginsenoside Rbl and the role of Nrf2/HO-l pathway in the pathophysiology of II/R injury.Part I:The mechanism of Nrf2/HO-l pathway in acute lung injury induced by intestinal ischemia reperfusion in mice.Objective:To investigate the mechanism of Nrf2/HO-l pathway in acute lung injury (ALI) induced by intestinal ischemia reperfusion (II/R) in mice.Methods:Male C57BL/6J mice were randomly divided into3groups:(1) Sham group (S group);(2) Intestinal Ischemia Reperfusion group (I/R group);(3) ATRA+I/R group (ATRA+I/R group). Lung histology was observed and evaluated. Interleukin-6(IL-6), interleukin-10(IL-10), tumor necrosis factor-a (TNF-a), superoxide dismutase (SOD) and malondialdehyde (MDA) in lung tissues were measured. The imunohistochemical and western blot analysis were performed to observe the expression of nuclear factor erythroid2-related factor2(Nrf2) and heme oxygenase-1(HO-1) in lung tissues.Results:Intestinal ischemia reperfusion (II/R) induced lung injury, which was characterized by edema, hemorrhage and neutrophil infiltration in the lung tissues as well as the significant increase of MDA, IL-6and TNF-a levels (P<0.05,I/R group and ATRA+I/R group vs S goup) and decrease of SOD and IL-10levels (P<0.05,I/R group and ATRA+I/R group vs S group) in the lung tissues. Expressions of Nrf2and HO-1in I/R group were higher than those in S group (P<0.05); Expressions of HO-1in ATRA+I/R group were lower than those in I/R group (P<0.05)Conclusion:Intestinal ischemia reperfusion can induced acute lung injury by activating Nrf2/HO-1pathway. Part Ⅱ:The effects of ginsenoside Rbl on acute lung injury induced by intestinal ischemia reperfusion in mice.Objective:To investigate the effects of ginsenoside Rbl on acute lung injury (ALI) induced by intestinal ischemia reperfusion (II/R) in mice and the role of Nrf2/HO-1pathway in the pathophysiologic process.Methods:Male C57BL/6J mice were randomly divided into3groups:(1)Intestinal Ischemia Reperfusion+60mg/kg ginsenoside Rbl (I/R+Rb1group);(2)ATRA+I/R group(ATRA+I/R group);(3)ATRA+I/R+60mg/kg ginsenoside Rbl (ATRA+I/R+Rbl group). Lung histology was observed and evaluated. Interleukin-6(IL-6), interleukin-10(IL-10), tumor necrosis factor-a (TNF-a), superoxide dismutase (SOD) and malondialdehyde (MDA) in lung tissues were measured. The imunohistochemical and western blot analysis were performed to observe the expression of nuclear factor erythroid2-related factor2(Nrf2) and heme oxygenase-1(HO-1) in lung tissues.Results:Intestinal ischemia reperfusion (II/R) induced lung injury, which was characterized by edema, hemorrhage and neutrophil infiltration in the lung tissues as well as the significant increase of MDA, IL-6and TNF-a levels and decrease of SOD and IL-10levels in the lung tissues. After administration of ginsenoside Rbl, the histological injury of lung was reduced. When compared with I/R group (Part1), the lung water content and the levels of MDA, IL-6and TNF-a were decreased, and the levels of SOD and IL-10were increased significantly (P<0.05), while expressions of Nrf2and HO-1in I/R+Rbl group were higher than those in I/R group (P<0.05). The parameters measured had no difference when either comparing ATRA+I/R with I/R group. Compared with I/R+Rbl group, MDA, IL-6and TNF-a levels were increased (P<0.05) and SOD and IL-10levels were decreased (P<0.05) in the lung tissues of ATRA+I/R+Rb1group. Besides, the cytoplasmic HO-1expression was lower in ATRA+I/R+Rbl group than in I/R+Rb1group but the nuclear Nrf2expression seemed no significant difference between these groups.Conclusion:Ginsenoside Rbl attenuates acute lung injury induced by intestinal ischemia reperfusion by activating Nrf2/HO-1pathway. |
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