| The damage caused by ischemia and then reperfusion in liver is called hepatic ischemia-reperfusion injury (HIRI). HIRI occurs as a consequence of trauma and hemorrhagic shock as well as temporary clamping of the hepato-duodenal ligament during liver resection. This injury could be severe enough to lead to a significant liver failure. The mechanisms involved in the production of the tissue damage by the HIRI are complex. In simple terms, the sequence of ischaemia followed by reperfusion results in the activation of Kupffer cells and polymorphonucleocytes resulting in the production of reactive oxygen species (ROS), cytokines, mitochondrial dysfunction, intracellular calcium overload and microcirculatory dysfunction leading to liver parenchymal damage. Modulation of HIRI can be achieved in various ways. These include hypothermia, ischaemic preconditioning, pharmacological agents to decrease HIRI, genetic modulation of HIRI, and machine perfusion. But so far, none of these interventions can be recommended in clinical practice. Because the current protective strategies have not been properly resolve the HIRI induced liver dysfunction. Gaseous signal molecule is a hot topic of research in recent years. For several centuries, hydrogen sulfide (H2S) had been known to be highly toxic. However, more recently H2S has been recognized as mediating a wide range of physiological effects. In addition, the role that II2S plays in attenuating ischaemia-reperfusion injury has begun to be elucidated. The most studies focus on the cytoprotective roles of H2S in the heart and the nervous in the setting of ischaemia-reperfusion injury and the mechanisms of cytoprotection. But whether H2S also has a protective effect on HIRI rarely reported.In this study, using a rat model of HIRI, we investigated the impact of hydrogen sulfide postconditioning on hepatic ischemia-reperfusion injury in rats. We also examined the role of ATP sensitive potassium channel and the changes of thioredoxin system in attenuation of hepatic ischemia-repeerfusion injury by hydrogen sulfide postconditioning in rats. Part I Effects of hydrogen sulfide postconditioning on hepatic ischemia-reperfusion injury in ratsObjective To investigate the effects of hydrogen sulfide postconditioning on hepatic ischemia-reperfusion injury in rats.Methods Thirty healthy male SD rats weighing220-250g were randomly divided into5groups (n=6each):shame operaton group (Sham group), ischemia-reperfusion group (IR group) and different doses of hydrogen sulfide groups (H2S1-3groups). In S group hepatic portal was only exposed but not ligated. In IR group the left and middle lobes of hepatic pedicle, portal vein and hepatic artery were clamped for60min and then reperfused. H2S1-3groups were received intraperitoneal injection of NaHS (14,28,56μmol·kg-1) at5min before reperfusion. Blood samples were collected for measuring the activity of alanine transaminase (ALT) and aspartate transaminase (AST) in serm at6h after reperfusion. Liver tissue samples were collected for measurement the glutathione (GSH) content and pathologic examination.Results Compared with S group, the activities of ALT and AST in serm was increased, GSH content in liver tissue decreased in IR group; Compared with IR group, the activities of ALT and AST in serm was decreased, GSH content in liver tissue increased in H2S1-3groups. Hepatic tissue pathologic injury was reduced in H2S1-3groups as compared with IR group.Conclusion Hydrogen sulfide postconditioning can reduce hepatic ischemia-reperfusion injury in rats.Part II Role of ATP sensitive potassium channel in attenuation of hepatic ischemia-reperfusion injury by hydrogen sulfide postconditioning in ratsObjective To investigate the role of ATP sensitive potassium channel in attenuation of hepatic ischemia-repeerfusion injury by hydrogen sulfide postconditioning in rats.Methods Thirty healthy male SD rats weighing220-250g were randomly divided into5groups (n=6each):shame operaton group (Sham group), ischemia-reperfusion group (IR group), NaHS group (NaHS group), Glibenclamide+NaHS group (Gli group) and5-hydroxydecanoate+NaHS group (5-HD group). All rats except for those in the sham group were subjected to hepatic ischemia for60min and followed by reperfusion for6hours. In NaHS group, rats were intraperitoneally administered NaHS (28μmol·kg-1)5min before hepatic reperfusion. In G group, rats were administered Glibenclamide (6mg·kg-1)5min before NaHS administration. In Gli group, rats were administered5-HD (10mg·kg-1)5min before NaHS administration. Blood samples were collected for measurement of alanine transaminase (ALT) and aspartate transaminase (AST). Liver tissue samples were collected for measurement TNF-α, MPO content and pathologic examination.Results Compared with S group, the activities of ALT and AST in serum were increased, TNF-α and MPO content in liver tissue were increased in IR group; Compared with IR group, the activities of ALT and AST in serum were decreased, TNF-α and MPO content in liver tissue were decreased in H2S groups. Hepatic tissue pathologic injury was reduced in H2S groups as compared with IR group. Compared with H2S group, the activities of ALT and AST in serum were increased, TNF-α and MPO content in liver tissue were increased in G group and5-HD group. Hepatic tissue pathologic injury was aggravated in G group and5-HD group as compared with H2S group.Conclusion Hydrogen sulfide postconditioning can protect liver from ischemia-reperfusion injury by activating the ATP sensitive potassium channel and decreasing the release of inflammatory factors.Part Ⅲ The changes of thioredoxin system in attenuation of hepatic ischemia-reperfusion injury by hydrogen sulfide postconditioning in ratsObjective To investigate the relationship between the protection of hydrogen sulfide against hepatic ischemia-reperfusion injury and thioredoxin system in rats.Methods Eighteen healthy male SD rats weighing220-250g were randomly divided into3groups (n=6each):shame operaton group (Sham group), ischemia-reperfusion group (IR group) and hydrogen sulfide groups (NaHS group). In S group hepatic portal was only exposed but not ligated. In IR group the left and middle lobes of hepatic pedicle, portal vein and hepatic artery were clamped for60min and then reperfuse. H2S groups were received intraperitoneal injection of NaHS (28μmol-kg"’) at5min before reperfusion., After6hours reperfusion, liver tissue samples were collected for measurement of Trx and TrxR activity by ELISA, Western-blot detection of Trx system proteins and TXNIP expression.Results Compared with S group, IR group decreased Trx activity and Trxl protein expression decreased, TXNIP protein expression increased (P<0.05); Compared with S group, NaHS group increased Trx activity and Trxl protein expression, TXNIP protein expression decreased (P<0.05),Conclusion Hydrogen sulfide postconditioning can reduce hepatic ischemia-reperfusion injury by inhibiting the expression of TXNIP and up-regulating the expression of Trx1in rats. |
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