The organ specificity in pathological damage of chronic intermittent hypoxia: an experimental study on rat with high-fat diet.

PURPOSE: It is known today that sleep apnea hypopnea syndrome and its characteristic chronic intermittent hypoxia can cause damages to multiple organs, including the cardiovascular system, urinary system, and liver. It is still unclear, however, whether the damage caused by sleep apnea hypopnea syndrome and the severity of the damage are organ-specific. METHODS: This research observed the pathological effects of chronic intermittent hypoxia on rat's thoracic aorta, myocardium, liver, and kidney, under the condition of lipid metabolism disturbance, through establishing the rat model of chronic intermittent hypoxia with high-fat diet by imitating the features of human sleep apnea hypopnea syndrome. In this model, 24 male Wistar rats were randomly divided into three groups: a control group fed by regular diet, a high-fat group fed by high-fat diet, and a high-fat plus intermittent hypoxia group fed by high-fat diet and treated with intermittent hypoxia 7 h a day. At the end of the ninth week, the pathological changes of rat's organs, including the thoracic aorta, myocardium, liver, and kidney are observed (under both optical microscopy and transmission electron microscopy). RESULTS: As the result of the experiment shows, while there was no abnormal effect observed on any organs of the control group, slight pathological changes were found in the organs of the high-fat group. For the high-fat plus intermittent hypoxia group, however, remarkably severer damages were found on all the organs. It also showed that the severity of the damage varies by organ in the high-fat plus intermittent hypoxia group, with the thoracic aorta being the worst, followed by the liver and myocardium, and the kidney being the slightest. CONCLUSIONS: Chronic intermittent hypoxia can lead to multiple-organ damage to rat with high-fat diet. Different organs appear to have different sensitivity to chronic intermittent hypoxia.

An experimental research on chronic intermittent hypoxia leading to liver injury.

PURPOSE: Sleep apnea-hypopnea syndrome and its chronic intermittent hypoxia component may cause multi-system-targeted injury. The latest finding shows that liver is one of the injured organs. The purpose of the study is to observe the dynamic process of the influence that chronic intermittent hypoxia plays on rat liver enzyme, hepatic histology, and ultrastructure based on lipid disorders. METHODS: A total of 72 male Wistar rats were randomly divided into three groups. The control group was fed with a regular chow diet, the high fat group with a high fat diet, and the high fat plus intermittent hypoxia group with a high fat diet with a 7-h/day intermittent hypoxia treatment. Changes were observed in rat liver enzyme, hepatic histology, and ultrastructure of the three groups on the third, sixth, and ninth weeks, respectively. The liver paraffin sections were detected with myeloperoxidase. RESULTS: The liver function and structure of the control group were found to be normal; the liver enzyme level of the high fat group was significantly higher than that of the control group on the sixth and ninth weeks; and the liver enzyme level of the high fat plus intermittent hypoxia group was significantly higher than that of the control group and the high fat group on the third, sixth, and ninth weeks (all P < 0.01). Observed by a light microscope and a transmission electron microscope, the high fat group and the high fat plus intermittent hypoxia group were all characterized by nonalcoholic fatty liver disease: the high fat group was characterized by simple fatty liver on the third and sixth weeks and by steatohepatitis on the ninth week; the damage of the high fat plus intermittent hypoxia group was significantly more severe than that of the high fat group in all the monitoring points, characterized by steatohepatitis on the sixth week and by obvious liver fibrosis on the ninth week; the myeloperoxidase level of the high fat plus intermittent hypoxia group was significantly higher than that of the control group and the high fat group (all P < 0.01). CONCLUSIONS: Under the conditions of high fat and intermittent hypoxia, the injury to the liver function, hepatic histology, and ultrastructure is more severe than that of the high fat group. The injury mainly was characterized by nonalcoholic fatty liver disease and becomes more severe with increased exposure time. Oxidative stress may play an important role in the mechanism.

[Effects of high-fat plus ethanol diet on myocardial ultrastructure in rats].

OBJECTIVE: To study the effects of high-fat plus ethanol diet on myocardial ultrastructure in rats. METHODS: 40 male SD rats in seventy-eight-week old were randomly divided into four groups: group A was control group, fed with common feedstuff; group B was high-fat diet group, freely foraging high-fat feedstuff; group C was ethanol group, the rats were intragastrically administered 60% ethanol solution twice a day by 1 ml/kg; group D was high-fat diet and ethanol group, the rats freely foraged high-fat feedstuff, and ethanol solution was intragastrically administered as before. After 12 weeks, blood samples were taken through jugular vein, the concentration of blood cholesterol (TG), triglycerides (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), apolipoprotein A1 (Apo-A1), apolipoprotein B (Apo-B), and alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) were determined. The cardiac index was also determined for all groups and the cardiac morphous were observed by high resolution Doppler ultrasound, and myocardial ultrastructure was observed by transmission electron microscope. RESULTS: After experiment, TG levels of groups A, B, C, D were (1.07 +/- 0.21), (2.34 +/- 0.72), (1.33 +/- 0.42) and (1.75 +/- 0.65) mmol/L, respectively (F = 8.323, P = 0.000); TC levels were (1.74 +/- 0.38), (5.66 +/- 1.74), (1.70 +/- 0.44) and (5.65 +/- 2.95) mmol/L, respectively (F = 13.670, P = 0.000); HDL levels were (0.65 +/- 0.11), (2.99 +/- 0.54), (0.52 +/- 0.13) and (2.06 +/- 0.26) mmol/L, respectively (F = 112.225, P = 0.000); LDL levels were (0.74 +/- 0.22), (1.87 +/- 0.90), (0.60 +/- 0.26) and (1.54 +/- 0.78) mmol/L, respectively (F = 7.318, P = 0.001); Apo-A1 levels were (0.25 +/- 0.10), (0.31 +/- 0.14), (0.21 +/- 0.05) and (0.36 +/- 0.11) g/L, respectively (F = 3.015, P = 0.047); Apo-B levels were (0.18 +/- 0.03), (0.11 +/- 0.04), (0.16 +/- 0.03) and (0.39 +/- 0.13) g/L, respectively (F = 15.621, P = 0.000); ALT levels were (111.25 +/- 20.18), (447.13 +/- 89.25), (173.13 +/- 44.01) and (198.25 +/- 39.81) U/L, respectively (F = 58.708, P = 0.000); AST levels were (105.50 +/- 9.99), (483.00 +/- 16.80), (120.75 +/- 5.09) and (276.88 +/- 10.48) U/L, respectively (F = 1906.624, P = 0.000);TBIL levels were (1.35 +/- 0.12), (1.66 +/- 0.18), (1.89 +/- 0.15) and (2.68 +/- 0.35)U/L, respectively (F = 55.006, P = 0.000); cardiac indexes were (3.02 +/- 0.22)%, (3.21 +/- 0.16)%, (3.26 +/- 0.26)% and (3.43 +/- 0.27)%, respectively (F = 16.150, P = 0.000). There were changes of cardiac morphous in group C and D, but not in group A and B; the myocardial ultrastructure was normal in Group A, but light to heavy changes were found in group B, C and D. CONCLUSION: High-fat diet and excessive intake of ethanol significantly induce abnormal lipid metabolism. High-fat diet induces the changes of myocardial ultrastructure before cardiac morphous and electrocardiogram, and intake of ethanol changes cardiac muscle in microstructure and macroscopy. High-fat diet plus ethanol may worsen this injury farther.