AIM： To assess the effect of notoginsenoside R1 on hepatic microcirculatory disturbance induced by gut ischemia/reperfusion （I/R） in mice. METHODS： The superior mesenteric artery （SMA） of C57/BL mice was ligated...AIM： To assess the effect of notoginsenoside R1 on hepatic microcirculatory disturbance induced by gut ischemia/reperfusion （I/R） in mice. METHODS： The superior mesenteric artery （SMA） of C57/BL mice was ligated for 15 min to induce gut ischemia followed by 30-rain reperfusion. In another set of experiments, R1 was continuously infused （10 mg/kg per hour） from 10 min before I/R until the end of the investigation to study the influence of R1 on hepatic microcirculatory disturbance induced by gut I/R. Hepatic microcirculation was observed by inverted microscopy, and the vascular diameter, red blood cell （RBC） velocity and sinusoid perfusion were estimated. Leukocyte rolling and adhesion were observed under a laser confocal microscope. Thirty and 60 min after reperfusion, lactate dehydrogenase （LDH）, alanine aminotransferase （ALl＇） and aspartate transaminase （AST） in peripheral blood were determined. The expression of adhesion molecules CD11b/CD18 in neutrophils and tumor necrosis factor- alpha （TNF-α）, interleukin-6 （IL-6） and monocyte chemotactic protein-1 （MCP-1） in plasma were evaluated by flow Oltometry. E-selectin and intercellular adhesion molecule-1 （ICAM-1） in hepatic tissue were examined by immunofluorescence.RESULTS： After gut I/R, the diameters of terminal portal venules and central veins, RBC velocity and the number of perfused sinusoids were decreased, while the leukocyte rolling and adhesion, the expression of E-selectin in hepatic vessels and CD18 in neutrophils, IL-6, MCP-1, LDH, ALT and AST were increased. R1 treatment attenuated these alterations except for IL-6 and MCP-1. CONCLUSION： R1 prevents I/R-induced hepatic microcirculation disturbance and hepatocyte injury, The effect of R1 is related to its inhibition of leukocyte rolling and adhesion by inhibiting the expression of E-selectin in endothelium and CD18 in neutrophils.展开更多
Background and Aims:Hepatic ischemia/reperfusion(I/R)injury has become an inevitable issue during liver transplantation,with no effective treatments available.However,peptide drugs provide promising regimens for the t...Background and Aims:Hepatic ischemia/reperfusion(I/R)injury has become an inevitable issue during liver transplantation,with no effective treatments available.However,peptide drugs provide promising regimens for the treatment of this injury and peptidomics has gradually attracted increasing attention.This study was designed to analyze the spectrum of peptides in injured livers and explore the potential beneficial peptides involved in I/R injury.Methods:C57BL/6 mice were used to establish a liver I/R injury animal model.Changes in peptide profiles in I/R-injured livers were analyzed by mass spectrometry,and the functions of the identified peptides were predicted by bioinformatics.AML12 cells were used to simulate hepatic I/R injury in vitro.After treatment with candidate liver-derived peptides(LDPs)1–10,the cells were collected at various reperfusion times for further study.Results:Our preliminary study demonstrated that 6 h of reperfusion caused the most liver I/R injury.Peptidomic results suggested that 10 down-regulated peptides were most likely to alleviate I/R injury by supporting mitochondrial function.Most importantly,a novel peptide,LDP2,was identified that alleviated I/R injury of AML12 cells.It increased cell viability and reduced the expression of inflammation-and apoptosis-related proteins.In addition,LDP2 inhibited the expression of proteins related to autophagy.Conclusions:Investigation of changes in the profiles of peptides in I/R-injured livers led to identification of a novel peptide,LDP2 with potential function in liver protection by inhibiting inflammation,apoptosis,and autophagy.展开更多
基金Supported by Tianjin Tasly Group, Tianjin, China
文摘AIM： To assess the effect of notoginsenoside R1 on hepatic microcirculatory disturbance induced by gut ischemia/reperfusion （I/R） in mice. METHODS： The superior mesenteric artery （SMA） of C57/BL mice was ligated for 15 min to induce gut ischemia followed by 30-rain reperfusion. In another set of experiments, R1 was continuously infused （10 mg/kg per hour） from 10 min before I/R until the end of the investigation to study the influence of R1 on hepatic microcirculatory disturbance induced by gut I/R. Hepatic microcirculation was observed by inverted microscopy, and the vascular diameter, red blood cell （RBC） velocity and sinusoid perfusion were estimated. Leukocyte rolling and adhesion were observed under a laser confocal microscope. Thirty and 60 min after reperfusion, lactate dehydrogenase （LDH）, alanine aminotransferase （ALl＇） and aspartate transaminase （AST） in peripheral blood were determined. The expression of adhesion molecules CD11b/CD18 in neutrophils and tumor necrosis factor- alpha （TNF-α）, interleukin-6 （IL-6） and monocyte chemotactic protein-1 （MCP-1） in plasma were evaluated by flow Oltometry. E-selectin and intercellular adhesion molecule-1 （ICAM-1） in hepatic tissue were examined by immunofluorescence.RESULTS： After gut I/R, the diameters of terminal portal venules and central veins, RBC velocity and the number of perfused sinusoids were decreased, while the leukocyte rolling and adhesion, the expression of E-selectin in hepatic vessels and CD18 in neutrophils, IL-6, MCP-1, LDH, ALT and AST were increased. R1 treatment attenuated these alterations except for IL-6 and MCP-1. CONCLUSION： R1 prevents I/R-induced hepatic microcirculation disturbance and hepatocyte injury, The effect of R1 is related to its inhibition of leukocyte rolling and adhesion by inhibiting the expression of E-selectin in endothelium and CD18 in neutrophils.
基金supported by National Natural Science Foundation of China (82070634,82002495)Shanghai Natural Science Foundation (20ZR1451700)+3 种基金SJTU CrossDisciplinary Research Fund in Medicine and Engineering (YG2022QN117)Shanghai Key Medical Specialty Fund (ZK2019A15)Research Fund of Key Laboratory for Translational Research and Innovative Therapeutics of Gastrointestinal Oncology (ZDSYS-2021-04)National Key Research and Development Program (2021YFC2701903).
文摘Background and Aims:Hepatic ischemia/reperfusion(I/R)injury has become an inevitable issue during liver transplantation,with no effective treatments available.However,peptide drugs provide promising regimens for the treatment of this injury and peptidomics has gradually attracted increasing attention.This study was designed to analyze the spectrum of peptides in injured livers and explore the potential beneficial peptides involved in I/R injury.Methods:C57BL/6 mice were used to establish a liver I/R injury animal model.Changes in peptide profiles in I/R-injured livers were analyzed by mass spectrometry,and the functions of the identified peptides were predicted by bioinformatics.AML12 cells were used to simulate hepatic I/R injury in vitro.After treatment with candidate liver-derived peptides(LDPs)1–10,the cells were collected at various reperfusion times for further study.Results:Our preliminary study demonstrated that 6 h of reperfusion caused the most liver I/R injury.Peptidomic results suggested that 10 down-regulated peptides were most likely to alleviate I/R injury by supporting mitochondrial function.Most importantly,a novel peptide,LDP2,was identified that alleviated I/R injury of AML12 cells.It increased cell viability and reduced the expression of inflammation-and apoptosis-related proteins.In addition,LDP2 inhibited the expression of proteins related to autophagy.Conclusions:Investigation of changes in the profiles of peptides in I/R-injured livers led to identification of a novel peptide,LDP2 with potential function in liver protection by inhibiting inflammation,apoptosis,and autophagy.
文摘复制 Wistar 大鼠肠缺血再灌注肝损伤模型,分假手术组、对照组、长春新碱预处理组、糖皮质激素保护组4组。检测指标:肝毛细血管通透性、组织丙二醛、血清乳酸脱氢酶 LDH_5、肝组织病理学。结果:长春新碱预处理动物,由于肝内中性粒细胞(NT)浸润少,肝损伤减轻,各项指标与对照组相比有显著差异(P<0.05);糖皮质激素部分抑制 NT 肝内浸润,肝损伤明显改善。认为肠道缺血再灌注时,肝损伤是由于 NT 局部浸润激活所介导的;糖皮质激素具有抗损伤作用。
