| Objective: Obstructive sleep apnea(OSA)patients are more likely to develop metabolic syndrome,non-alcoholic fatty liver disease and cognitive impairment than normal people.The mechanism may be related to organ damage caused by intermittent hypoxia(IH).Autophagy is a main regulatory mechanism for the maintenance of cell homeostasis,which can be activated by hypoxia,starvation,stress and the other conditions.The activation of autophagy is often associated with injury,then lead to cell apoptosis and a variety of diseases.Intermittent hypoxia is a special form of hypoxia.It has been found that cardiomyocytes can be damaged under the exposure of IH,and the damage is accompanied by increased autophagy.In our previous study,we found that not only apoptosis occurred in the hippocampal neurons,but also autophagy was activated by IH.It is unknown that whether the same situation could appears in the kidney,liver,and pancreas.Thus,we established an intermittent hypoxia rat model to observe the damage and autophagy of hippocampus,myocardium,kidney,liver and pancreas under the exposure of intermittent hypoxia by HE staining,electron microscopy and immunohistochemistry.Methods: 12 maleSD rats(n=6/group)were randomly assigned to two groups: a control group(CON)with normal oxygen and an intermittent hypoxia group(CIH: 5-21% FiO2,120 s cycle,8h/day).Organs mentioned above were removed after 6 weeks of IH,the pathological changes of organs were observed by HE staning,ultrastructural changes and autophagosome were observed by transmission electron microscope,and the expression of light chain 3(LC3)was assessed by Immunohistochemistry.Results:1.Hippocampal tissue: there was no obvious pathological damage and ultrastructural changes in the control group.The nucleus of hippocampal neurons in the intermittent hypoxia group was deeply stained,the double layer membrane structure could be observed under the electron microscope,and the expression of autophagy marker LC3 was increased.2.Myocardial tissue: Result of HE staining showed that the myocardial cells in the control group were neatly arranged.For the IH group,the myocardial cells were swollen and irregularly arranged,the myocardial fibers were broken.Besides,the myocardium of the control group was rich in mitochondria observed under the electron microscope,while the mitochondria were swelling and the double layer membrane structures can be seen in intermittent hypoxia group.The immunohistochemistry showed that the expression of autophagy marker LC3 increased.3.Renal tissue: HE staining showed that the structure of renal tubule was basically normal in the control group.The glomerular capillaries were mild ischemia with a reduction of erythrocytes.The injury of renal tubular was more obvious than that of glomerular in IH group,besides,the degeneration,of renal tubular epithelial stenosis of the lumen and a small amount of inflammatory cell infiltration can be seen.In transmission electron microscopy,the mitochondrial crista was widened and the mitochondria were swelled.The brown yellow granules of the autophagy protein are mainly concentrated in the renal tubular epithelial cells.4.Liver tissue: HE staining showed that the liver plate in the control group was neatly arranged and the cell morphology was basically normal.The hepatocytes in the intermittent hypoxia group were swelling and sparsely compared with the control group.The double layer membrane structure and vacuoles were found under the electron microscope.The immunohistochemistry showed that the expression of autophagy marker LC3 increased.5.Pancreatic tissue: HE staining showed that the cell structure of the pancreas in the control group was basically normal,and the cells in the intermittent hypoxia group were swollen and arranged in disorder.Under the electron microscope,the structure of the double layer membrane increased,but unlike the other tissues,the inclusions were the endoplasmic reticulum.The immunohistochemistry showed that the expression of autophagy marker LC3 increased.6.The pathological injury degree of each organ is different: For example,in hippocampus tissue cells,there were no obvious change in pathological and ultrastructural changes after intermittent hypoxia,while in renal tissue,there are obvious cell degeneration and inflammatory infiltration in intermittent hypoxia group,and the injury was mainly in renal tubular.7.Autophagy occurred in all of the five organs we observed,but the characteristic was varies in different organs.For example,the mitochondria autophagy were mainly occurred in mitochondrion rich organs such as the hippocampus and the myocardium,while the endoplasmic reticulum autophagy were mainly observed in the secreted exuberant organs such as the pancreas.Conclusions: This study suggests that IH may induce the injury of multiple organs,including hippocampus,myocardium,kidney,liver and pancreas,and the degree of injury was different.The increase of autophagy is accompanied by the occurrence of injury and it appears to be selective. |
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