ObjectiveTo detect the expression level of phosphate and tension homolog deleted on chromsome ten(PTEN) and its downstream signal molecules phosphorylated protein kinase B (p-AKT) in liver cells of rats during intermittent hypoxia,to investigate the effect of PTEN and p-AKT of liver cells on insulin resistance which intermittent hypoxia is relevant. MethodsA total of 24 healthy male SD rats were selected and divided into 3 groups randomly,ie.CIA (chronic intermittent air) group,CIH4 (chronic intermittent hypoxia for 4 weeks) group,and CIH8 (chronic intermittent hypoxia for 8 weeks) group. The fasting blood glucose,fasting insulin,PTEN and p-AKT expressions in the liver cells were detected. The insulin resistance was evaluated systematically by the insulin sensitive index (ISI) and homeostasis model assessment of insulin resistance (HOMA-IR). Average gray value was used to represent the protein expressions of PTEN and p-AKT. ResultsCompared with CIA group,the decline of ISI in CIH4 group and CIH8 group was significant (P<0.05). Furthermore,the decline in CIH8 group was more significant than that in CIH4 group (P<0.05). Compared with CIA group,the rise of HOMA-IR in CIH4 and CIH8 groups was statistically significant (P<0.05). In addition,the rise in CIH8 group was more significant than that in CIH4 group (P<0.05). Compared with CIA group,there was a significant rise in the protein expressions of PTEN in CIH4 and CIH8 groups (P<0.05). Compared with CIH4 group,the rise of the protein expressions of PTEN in CIH8 group was still statistically significant (P<0.05). Compared with CIA group,there was a significant decline in the protein expressions of p-AKT in CIH4 and CIH8 groups (P<0.05). Compared with CIH4 group,the decline of protein expression of p-AKT in CIH8 group was still of statistical significance (P<0.05). There was a significantly increasing trend for the expression of PTEN in the liver cells of rats with intermittent hypoxia along with the decline of ISI and rise of HOMA-IR. The expression increased significantly with the longer duration of intermittent hypoxia. The expression of p-AKT in liver cells of rats with intermittent hypoxia decreased along with the decline of ISI and rise of HOMA-IR. Furthermore,the decline tendency was more significant with the long duration of intermittent hypoxia. ConclusionThe fasting blood glucose of rats and insulin level increase due to the chronic intermittent hypoxia,resulting in the insulin resistance. The degree of insulin resistance increases with the longer duration of intermittent hypoxia. The expression of PTEN protein increases with intermittent hypoxia,and that of p-AKT protein decreases,which is obviously correlated with ISI and HOMA-IR. It is indicated that the PTEN protein possibly play an important role in the mechanism of insulin resistance for rats with intermittent hypoxia.
Objective To explore the mechanism of chronic intermittent hypoxia (CIH) on renal damage with normal diet and high-fat diet. Methods Twenty-four healthy male Wistar rats of SPF grade were randomly divided into 4 groups (n=6 in each group), namely group A (normoxia and common diet), group B (normoxia and high fat diet), Group C (CIH and common diet), and group D (CIH and high fat diet). The serum cystatin C (Cys-C) was measured and the renal CHOP protein was detected by immunohistochemistry. The ultrastructural changes of glomeruli and renal tubules were observed under electron microscope. Results The levels of Cys-C in group B, group C and group D were significantly higher than those in group A (P<0.05). The mean density of endoplasmic reticulum stress (ERS) marker protein CHOP in group B, group C and group D was significantly higher than that in group A (P<0.05). Electron microscope revealed focal nuclear pyknosis in the partly renal tubular epithelial cells, sparse and scattered brush border in group B and group C, also revealed nuclear pyknosis in a large number of tubular epithelial cells, sparse and scattered brush border in group D. Conclusion CIH can activate the ERS mediated renal tubular epithelial apoptosis, thus induce ultrastructure changes and damage of kidney.
ObjectiveTo investigate the expression and significance of CD73 in rats with intermittent hypoxia and high fat diet.MethodsThe rat model of chronic intermittent hypoxia combined with high fat diet was established. Twenty-four healthy male Wistar rats in the SPF level were randomly divided into 4 group, with 6 rats in each group, namely group A (normoxia and normal diet), group B (normoxia and high fat diet), group C (intermittent hypoxia and normal diet)and group D (intermittent hypoxia and high-fat diet). After 6 weeks of experiment, the serum lipid levels, myocardial morphological changes under microscope, the expression level of CD73 protein detected byimmunohistochemistry and Western blot in myocardial cells in rats were compared among these groups.ResultsThe serum lipid levels were significantly different among these groups (P<0.05). HE results showed that the myocardial cells of group A had no obvious abnormalities; disorganized visible myocardial fibers with focal necrosis in groups B and C; myocardial cell injury was most obvious in group D, in which visible muscle fibers arranged in disorder, and grain was not clear, part of the muscle fibers were dissolved predominantly. Compared with group A, CD73 protein expression levels in myocardial cells in groups B, C, and D were significantly elevated (P<0.01). Furthermore, CD73 protein expression level in myocardial cells in group D was significantly higher than those in groups B and C (P<0.01). Western blot showed consistent results as immunohistochemistry: compared with group A, CD73 protein expression levels in groups B, C, and D were significantly elevated (P<0.05), and CD73 protein expression level in myocardial cells in group D was significantly higher than those in groups B and C (P<0.01).ConclusionChronic intermittent hypoxia and high fat diet can cause myocardial cell damage and upregulate CD73 expression in the cardiomyocytes.
ObjectiveTo investigate the expression of C/EBP homologous protein (CHOP) in lung tissue of chronic intermittent hypoxia rats, and explore the intervention effect of edaravone and its possible mechanism.MethodsA total of 120 adult male Wistar rats were randomly divided into three groups: a normal control group (UC group), a chronic intermittent hypoxia group (CIH group), an edaravone intervention group (NE group), and a normal saline group (NS group). The above four groups were also randomly divided into five time subgroups of 3 days, 7 days, 14 days, 21 days and 28 days, respectively, with 6 rats in each time subgroup. The histopathological changes of lung tissue were observed by hematoxylin-eosin (HE) staining and the expression of CHOP in lung tissue was detected by immunohistochemical method.ResultsHE staining results showed that there was no obvious pathological change in UC group. The epithelial cells of lung tissue in CIH group showed edema, hyperemia, widening of alveolar septum and inflammatory cell infiltration. The pathological injury was more serious with the prolongation of intermittent hypoxia time. There were also pathological changes in NE group, but the degree of lung tissue injury was significantly lower than that in CIH group. The results of immunohistochemistry showed that the expression of CHOP in CIH group was significantly higher than that in UC group. The expression of CHOP in NE group was higher than that in UC group, but it was still significantly lower than that in CIH group.ConclusionsThe expression of CHOP protein in lung tissue of chronic intermittent hypoxic rats is enhanced and the high expression of CHOP protein plays a certain role in the lung injury of chronic intermittent hypoxia rats complicated with lung injury. Edaravone may protect lung tissue from chronic intermittent hypoxia by inhibiting the expression of CHOP.
Objective To investigate the changes in mitochondrial morphology, structure and function in rats with severe intermittent hypoxia, as well as the effects of intermittent hypoxia and its severity on cognitive function. Methods A total of 18 rats were selected to construct a model of severe intermittent hypoxia, which were divided into a normal control group, an intermittent air control group, and a 5% intermittent hypoxia group for 8 weeks, with 6 rats in each group. The structural and functional changes of mitochondria in the hippocampal CA1 region were observed. A total of 30 rats were randomly divided into 5 groups: a normal control group, an intermittent air control group, a 5% intermittent hypoxia 4-week group, a 5% intermittent hypoxia 6-week group, and a 5% intermittent hypoxia 8-week group, with 6 rats in each group. The cognitive function of the rats in each group was evaluated by Morris water maze experiment. Results In the mitochondria of the hippocampal CA1 region of severely intermittent hypoxic rats, bilayer membranes or multilayer membranes were visible, the mitochondria were swollen, cristae were broken and vacuolated, and their respiratory function was significantly weakened, the membrane permeability was increased, and the membrane potential was reduced. In the Morris water maze, there was no significant difference in swimming speed between the rats. With the prolongation of intermittent hypoxia action time, the latency of finding the hidden platform in each group of rats increased significantly, and the residence time of the target quadrant decreased significantly. Conclusions Mitochondrial structure in the hippocampal CA1 region of the rat brain is destroyed during severe intermittent hypoxia, and dysfunction and cognitive impairment occur. With the prolongation of intermittent hypoxic injury, the degree of cognitive impairment worsens.