ObjectiveTo study the changes of body weight, body length, tail length, femur length, bone mineral density, serum osteocalcin content and apoptosis of bone cells in rats under intermittent hypoxia condition, so as to explore the effects of intermittent hypoxia on bone growth.MethodsForty healthy male SD rats aged 3 to 4 weeks were selected and divided into 2 groups, 20 rats in each group. Group A: normoxic control group (normal diet and normoxic environment); group B: intermittent hypoxia group (normal feeding and was put into the hypoxic chamber to establish intermittent hypoxia environment), 8 hours a day (09:00 to 17:00), 4 weeks of modeling. The body weight, body length and tail length of the two groups were measured in every morning. At the end of 4 weeks after anesthesia, the body weight, body length, tail length and right femur length were measured. The body weight growth rate, body length growth rate and tail length growth rate were calculated. Blood samples were collected from the abdominal aortic, and the content of serum osteocalcin was measured by enzyme linked immunosorbent assay; the right femur bone mineral density was measured by automatic dual-energy X-ray bone densitometer; the apoptosis of bone cells was detected by immunofluorescence staining+TUNEL.ResultsThe body weight growth rate, body length growth rate, tail length growth rate and right femur length in group A were all higher than those in group B (P<0.05); serum osteocalcin content in group A was higher than that in group B (P<0.05); bone mineral density in group A was higher than that in group B (P<0.05); the apoptotic index of bone cells in group B was higher than that in group A (P<0.05). Pearson correlation analysis showed that the serum osteocalcin content was significantly positively correlated with the growth rate of body length, femoral length and bone mineral density (P< 0.01).ConclusionIntermittent hypoxia could reduce osteocalcin secretion, inhibit bone growth and sclerosis, and induce osteocyte apoptosis, thus delay the bone growth.
ObjectiveTo explore the mechanism of renal tubular epithelial cell apoptosis induced by endoplasmic reticulum stress in rats with intermittent hypoxia (IH) and the intervention effect of losartan.MethodsSixty SPF grade healthy male SD rats were randomly divided into four groups (15 rats in each group), namely as group A (control group), group B (IH group), group C (IH+losartan group), and group D (IH+saline group). The group C and D were intraperitoneally injected with losartan 30 mg/kg and the same dose of saline 30 minutes daily before the experiment, and then the group B, C and D were placed in the intermittent hypoxia chamber. After 6 weeks of modeling, serum of the rats was sampled to detect the renal function. Hematoxylin-eosin staining was used to observe histomorphological changes of the kidney; transmission electron microscopy was used to observe ultrastructural changes of the kidney; TUNEL was used to detect apoptotic index of the renal tubular epithelial cells; and RT-PCR method was used to detect expressions of caspase-12, JNK and CHOP mRNA in the kidney.ResultsThe differences of renal function among these four groups were statistically significant (all P<0.05). Hematoxylin-eosin staining and transmission electron microscopy showed the histomorphological and ultrastructural changes of the kidneys in group B, C and D compared with group A, and the damages in group B and D were more significant. TUNEL results showed that the apoptotic index of renal tubular epithelial cells in group B and D was significantly higher than that in group A (P<0.01), while that in group C was significantly lower than that in group B and D (all P<0.01). RT-PCR results showed that caspase-12, JNK and CHOP mRNA expressions were significantly higher in group B and D than those in group A (all P<0.01); caspase-12 mRNA expression was significantly lower in group C than that in group B and D (P<0.01; P<0.05); and CHOP mRNA expression was significantly lower in group C than that in group B and D (all P<0.01).ConclusionsIH may induce apoptosis of renal tubular epithelial cells by activating endoplasmic reticulum stress through caspase-12, JNK and CHOP. Losartan has protective effects on the kidney of rats with intermittent hypoxia. Its mechanism may be related to the inhibition of apoptotic pathways mediated by endoplasmic reticulum stress.
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.