AIM To investigate the underlying mechanisms of the protective role of remote ischemic perconditioning (RIPerC) in rat liver transplantation. METHODS Sprague-Dawley rats were subjected to sham, orthotopic liver transp...AIM To investigate the underlying mechanisms of the protective role of remote ischemic perconditioning (RIPerC) in rat liver transplantation. METHODS Sprague-Dawley rats were subjected to sham, orthotopic liver transplantation (OLT), ischemic postconditioning (IPostC) or RIPerC. After 3 h reperfusion, blood samples were taken for measurement of alanine aminotransferase, aspartate aminotransferase, creatinine (Cr) and creatinine kinase-myocardial band (CK-MB). The liver lobes were harvested for the following measurements: reactive oxygen species (ROS), H2O2, mitochondrial membrane potential (Delta psi m) and total nitric oxide (NO). These measurements were determined using an ROS/H2O2, JC1 and Total NOx Assay Kit, respectively. Endothelial NO synthase (eNOS) was analyzed by reverse transcription-polymerase chain reaction (RTPCR) and western blotting, and peroxynitrite was semiquantified by western blotting of 3-nitrotyrosine. RESULTS Compared with the OLT group, the grafts subjected to RIPerC showed significantly improved liver and remote organ functions (P < 0.05). ROS (P < 0.001) including H2O2 (P < 0.05) were largely elevated in the OLT group as compared with the sham group, and RIPerC (P < 0.05) reversed this trend. The collapse of Delta psi m induced by OLT ischemia/reperfusion (I/R) injury was significantly attenuated in the RIPerC group (P < 0.001). A marked increase of NO content and phosphoserine eNOS, both in protein and mRNA levels, was observed in liver graft of the RIPerC group as compared with the OLT group (P < 0.05). I/R-induced 3-nitrotyrosine content was significantly reduced in the RIPerC group as compared with the OLT group (P < 0.05). There were no significant differences between the RIPerC and IPostC groups for all the results except Cr. The Cr level was lower in the RIPerC group than in the IPostC group (P < 0.01). CONCLUSION Liver graft protection by RIPerC is similar to or better than that of IPostC, and involves inhibition of oxidative stress and up-regulation of the PI3K/Akt/eNOS/NO pathway.展开更多
Background:Remote ischemic perconditioning(RIPerC)has been demonstrated to protect grafts from hepatic ischemia-reperfusion injury(IRI).This study investigated the role of exosomes in RIPerC of liver grafts in rats.Me...Background:Remote ischemic perconditioning(RIPerC)has been demonstrated to protect grafts from hepatic ischemia-reperfusion injury(IRI).This study investigated the role of exosomes in RIPerC of liver grafts in rats.Methods:Twenty-five rats(including 10 donors)were randomly divided into five groups(n=5 each group):five rats were used as sham-operated controls(Sham),ten rats were for orthotopic liver transplantation(OLT,5 donors and 5 recipients)and ten rats were for OLT+RIPerC(5 donors and 5 recipients).Liver architecture and function were evaluated.Results:Compared to the OLT group,the OLT+RIPerC group exhibited significantly improved liver graft histopathology and liver function(P<0.05).Furthermore,the number of exosomes and the level of P-Akt were increased in the OLT+RIPerC group.Conclusions:RIPerC effectively improves graft architecture and function,and this protective effect may be related to the increased number of exosomes.The upregulation of P-Akt may be involved in underlying mechanisms.展开更多
基金Supported by National Natural Science Foundation of China,No.81421062the Science and Technology Bureau of Zhejiang Province,China,No.2016C33145+1 种基金the National Natural Science Foundation of China,No.81470891the 863 National High Technology Research and Development Program of China for young scientist No.2015AA020923
文摘AIM To investigate the underlying mechanisms of the protective role of remote ischemic perconditioning (RIPerC) in rat liver transplantation. METHODS Sprague-Dawley rats were subjected to sham, orthotopic liver transplantation (OLT), ischemic postconditioning (IPostC) or RIPerC. After 3 h reperfusion, blood samples were taken for measurement of alanine aminotransferase, aspartate aminotransferase, creatinine (Cr) and creatinine kinase-myocardial band (CK-MB). The liver lobes were harvested for the following measurements: reactive oxygen species (ROS), H2O2, mitochondrial membrane potential (Delta psi m) and total nitric oxide (NO). These measurements were determined using an ROS/H2O2, JC1 and Total NOx Assay Kit, respectively. Endothelial NO synthase (eNOS) was analyzed by reverse transcription-polymerase chain reaction (RTPCR) and western blotting, and peroxynitrite was semiquantified by western blotting of 3-nitrotyrosine. RESULTS Compared with the OLT group, the grafts subjected to RIPerC showed significantly improved liver and remote organ functions (P < 0.05). ROS (P < 0.001) including H2O2 (P < 0.05) were largely elevated in the OLT group as compared with the sham group, and RIPerC (P < 0.05) reversed this trend. The collapse of Delta psi m induced by OLT ischemia/reperfusion (I/R) injury was significantly attenuated in the RIPerC group (P < 0.001). A marked increase of NO content and phosphoserine eNOS, both in protein and mRNA levels, was observed in liver graft of the RIPerC group as compared with the OLT group (P < 0.05). I/R-induced 3-nitrotyrosine content was significantly reduced in the RIPerC group as compared with the OLT group (P < 0.05). There were no significant differences between the RIPerC and IPostC groups for all the results except Cr. The Cr level was lower in the RIPerC group than in the IPostC group (P < 0.01). CONCLUSION Liver graft protection by RIPerC is similar to or better than that of IPostC, and involves inhibition of oxidative stress and up-regulation of the PI3K/Akt/eNOS/NO pathway.
基金This study was supported by the Public Projects of Zhe-jiang Province(LGF21H030006)the Major Science and Tech-nology Projects of Hainan province(ZDKJ2019009)+2 种基金Research Project of Jinan Microecological Biomedicine Shandong Laboratory(JNL-2022002A,JNL-2022023C)Research Unit Project of Chinese Academy of Medical Sciences(2019-I2M-5-030)Innovative Re-search Groups of National Natural Science Foundation of China(81721091).
文摘Background:Remote ischemic perconditioning(RIPerC)has been demonstrated to protect grafts from hepatic ischemia-reperfusion injury(IRI).This study investigated the role of exosomes in RIPerC of liver grafts in rats.Methods:Twenty-five rats(including 10 donors)were randomly divided into five groups(n=5 each group):five rats were used as sham-operated controls(Sham),ten rats were for orthotopic liver transplantation(OLT,5 donors and 5 recipients)and ten rats were for OLT+RIPerC(5 donors and 5 recipients).Liver architecture and function were evaluated.Results:Compared to the OLT group,the OLT+RIPerC group exhibited significantly improved liver graft histopathology and liver function(P<0.05).Furthermore,the number of exosomes and the level of P-Akt were increased in the OLT+RIPerC group.Conclusions:RIPerC effectively improves graft architecture and function,and this protective effect may be related to the increased number of exosomes.The upregulation of P-Akt may be involved in underlying mechanisms.
