| Sepsis, a systemic inflammatory response syndrome (SIRS) induced by infection, turningitself to be one of the leading cause of mortality in critically ill patients.It may cause severesepsis,septic shock and Multiple Organ Dysfunction Syndrome(MODS). Liver is the target organvulnerable to attacks under sepsis; while hepatic insufficiency is the early performance of multipleorgan failure(MOF) caused by sepsis. The pathophysiology of the disease is not clear, it ischaracterized by cytokine storm, hypercoagulation, tissue hypoperfusion,immune suppression,mitochondrial dysfunction and oxygen supply-demand imbalance.Mitochondria are the metaboliccenter of nutrients and energy, and mitochondrial dysfunction plays an important role in the processof sepsis, especially those with sepsis shock. Aquaporin-8(AQP8), an aquaporin (AQP) channelpermeable to water, in the inner membrane of rat liver mitochondria is suggested to be a role formaintain the structure and the metabolic function of mitochondria. By studying the rats under sepsisstate caused by cecal ligation and puncture, it is aimed to investigate the change in mitochondriamorphology and the role of AQP8in sepsis-induced liver injury.ObjectivesTo study the alteration on the expression levels of aquaporin-8(AQP8)in the livermitochondria of rats with sepsis, and its role in the change of mitochondrial morphology,so as to explore the expression improvement of mitochondria AQP8with the expectation to protect the liver from sepsis mediated injury.Methods24SD rats were divided into two groups randomly, the control group and the septicgroup,12rats being in each group. The septic model was made by cecal ligation andpuncture, and perform sham operation in the control group to finish the experimentation.Record rats’ temperature, respiratory rate, heart rate variation and response to externalstimulation in both groups respectively, One hours after reaching the diagnostic criteriafor sepsis, rats were anesthetized and killed by decapitation；Livers were excised, partfor electron microscope sample preparation and the left for mitochondria isolation. Theexpression of AQP8in the hepatocyte mitochondria was detected using western blottingand the expression of AQP8mRNA was assayed by reverse transcription-polymerasechain reaction. It adopts statistic solution of SPSS13.0software and one-way ANOVAtest for counting data.Results1.Electron microscopy of the control group cell membranes were regular and withoutinterruptions, the number of endoplasmic reticulum and mitochondria was relativelyhigh and numerous well-formed. while in the septic group, mitochondria were swollenand pale, with indistinct cristae and disrupted membranes,vacuolization and indistinctrough endoplasmic reticulum were also present in the cytoplasm.2.Given prohibitin as the internal reference and AQP8/prohibitin as the relative level ofAQP8and determined relative level of AQP8in control group as1, that of AQP8insepsis group was0.61±0.08; it decreased about39%than that in the control group(P<0.01), and the differences between them had obvious statistical significance.3.Given β-actin as the internal reference and AQP8/β-actin as the relative transcriptlevel of AQP8mRNA and determined relative transcript level of AQP8mRNA in control group as1, that of AQP8mRNA in septic group was1.59±0.24; it increasedabout59%than that in the control group (P<0.01), and the differences between themhad obvious statistical significance.Conclusion1.The animal model of sepsis was established successfully by cecal ligation andpuncture.2. Sepsis can result in acute liver injury and obvious change in ultrastructure of livermitochondria;3. The expressive level of mitochondria AQP8protein decreases under sepsis state,which may be the main reason to the swollen and change of mitochondria;4. The expressive level of mitochondria AQP8protein decreases under sepsis state,while that of AQP8mRNA increases, implying the existence of compensatorymechanism, but for the posttranscriptional mechanism,AQP8protein does not return. |
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