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[ ABSTRACT] AIM: To investigate the effect of chronic intermittent hypoxia on AMP-activated protein kinase ( AMPK) pathway in the brain of young rats.METHODS:Part one:SD mice (3~4 weeks old) were randomly divided into 4 groups (n=8): simulated air control group for 2 weeks (2AC), chronic intermittent hypoxia group for 2 weeks (2IH), simulated air control group for 4 weeks (4AC) and chronic intermittent hypoxia group for 4 weeks (4IH).Part two:SD mice (3~4 weeks old) were randomly divided into 2 groups (n=8): chronic intermittent hypoxia group for 4 weeks (4IH) and chronic intermittent hypoxia group treated with AMPK inhibitor for 4 weeks (4IHI).After modeling, the eight-arm maze test was performed.TUNEL method was used to detect the neuronal apoptosis in the hippocampal and pre-frontal cortical tissues.The mRNA expression of adenosine A2a receptor was examined by RT-qPCR, and the protein levels of phosphorylated AMPK (p-AMPK) and mammalian target of rapamycin (p-mTOR) were determined by Western blot. RESULTS:Compared with control group, the numbers of reference memory error ( RME) , working memory error ( WME) and total error (TE) in 2IH group and 4IH group significantly increased (P<0.01).Compared with 2IH group, the num-bers of errors in 4IH group also increased significantly (P<0.01).Compared with 4IH group, the values in 4IHI group significantly decreased.Compared with control group, the neuronal apoptosis of hippocampus and prefrontal cortex in 2IH group and 4IH group increased, and that in 4IH group was more evident (P<0.05).In 4IHI group, the neuronal apopto-sis decreased.The mRNA expression of adenosine A2a receptor in the hippocampal and cortical tissues in 2IH group and 4IH group was higher than that in control group.The protein level of p-AMPK was higher, and p-mTOR was lower in 2IH group and 4IH group, and those in 4IH group were more evident (P<0.05).Compared with 4IH group, the protein level of p-AMPK was lower, and p-mTOR was higher in 4IHI group.CONCLUSION: Chronic intermittent hypoxia induces neuronal apoptosis, resulting in impairment of learning and memory in a time-dependent manner by upregulating adenosine A2a receptor, activating AMPK activity, and inhibiting mTOR phosphorylation in rats.
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<p><b>OBJECTIVE</b>To evaluate effectiveness therapeutic regimens for obstructive sleep apnea hypopnea syndrome (OSAHS) children at an acceptable cost.</p><p><b>METHOD</b>This study was performed at Yuying Children's Hospital of Wenzhou Medical University from Mar. 2008 to Dec. 2010. Prospective random number table method was used for the analysis; 60 children with mild OSAHS were divided into Mild OSAHS Montelukast Treatment (MM) group and Mild OSAHS Adenotonsillectomy Treatment (MAT) group. 32 children in MM group were treated with leukotriene receptor antagonists (LTRAs), while 28 children in MAT group were treated with adenotonsillectomy. Also, 58 children with moderate and severe OSAHS were divided into severe OSAHS Montelukast Treatment (SM) group and severe OSAHS Adenotonsillectomy Treatmen (SAT) group. Twenty-two children in SM group were treated with LTRAs, while 36 children in SAT group were treated with adenotonsillectomy. All selected children were evaluated by polysomnography (PSG) and Obstructive Sleep Apnea-18 (OSA-18) items before and after a six-month treatment. Both records were taken and analyzed, surgical complications and the reason for non-remission after operation were also analyzed. Two therapies were compared based on economic consideration and therapeutic effect. Result (1) PSG: A significant change of a significant change of Apnea Hypopnea Index (AHI) was observed in MM group after the treatment (before receiving the treatment 4.56 ± 1. 26, and after receiving the treatment 3. 48 ± 1. 52, t =3. 50, P <0. 05). But for oxygen desaturation Index (ODI) (MM group 2. 18 ± 2. 19, and MAT group 1. 80 ± 2. 34) and Lowest Oxygen satuation (LSaO2) (MM group 91. 66 ± 2. 34, and MAT group 92. 79 ± 2. 18), there was no significant difference in MM group and MAT group after the treatment (ODI, t =0. 65, and LSaO2 t = - 1. 93, P >0. 05). (2) OSA-18 scores: Significant differences were found in sleeping disorder (before 14. 81 ± 6. 28, and after 10. 56 ± 3. 57), the degree of familial stress (before 13. 56 ± 3. 54, and after 8. 97 ± 2. 96), and OSA-18 total scores (before 52. 66 ± 1. 11, and after 42. 56 6. 48) in MM group after the treatment (sleeping disorder Z - 3. 14, the degree of familial stress Z = -4. 50, and OSA-18 total scores Z= -4. 01, P <0. 05). (3) In addition to the cost of drugs, groups with surgical treatment had a larger economic burden than those with LTRAs treatment. (4) Treatment was totally effective for 28 children (88%) in MM group, and 28 children (100%) in MAT group. Meanwhile, treatment also achieved an obvious effect on 2 children (9%) in SM group, and in 35 children (97%) in SAT group. In MAT group, 3 children improved (11%). And in SAT group, 7 children improved (19%), but treatment was found to be ineffective in 1 case (3%). Among those effective and ineffective cases in groups with surgical treatment, there were 9 children with nasal diseases.</p><p><b>CONCLUSION</b>(1) Surgical treatment is recommended as the first choice for children with moderate and severe OSAHS. And for those who also suffer from nasal diseases, treatment combining drugs with surgery is necessary. (2) LTRAs therapy has a good effect for mild OSAHS. Surgery is also recommended when drugs could not achieve any obvious improvement in clinical symptoms of children with mild OSAHS.</p>
Subject(s)
Child , Humans , Adenoidectomy , Blood Gas Analysis , Cost of Illness , Oxygen , Polysomnography , Prospective Studies , Sleep Apnea, Obstructive , General Surgery , Sleep Wake Disorders , Tonsillectomy , Treatment OutcomeABSTRACT
AIM: To investigate the mechanism of renal damage in chronic intermittent hypoxia (CIH) rat model.METHODS:The Sprague-Dawley rats were randomly divided into 2-week CIH group (2IH), 2-week simulated air control group (2C), 4-week CIH group (4IH) and 4-week simulated air control group (4C).HE staining, PAS staining and Masson staining were used for histological evaluation .Blood was collected for the measurement of superoxide dismutase (SOD).The mRNA expression of hypoxia-inducible factor-1α(HIF-1α), manganese superoxide dismutase (MnSOD), copper/zinc superoxide dismutase ( Cu/ZnSOD ) was detected by real-time PCR.RESULTS: ( 1 ) No significance difference of renal weight , body weight , and the ratio of renal weight to body weight was observed , while IH caused mor-phologic kidney damage , especially in 4IH group.Hypertrophy of epithelial cells in the kidney tubles and dilation in the glomeruli were observed under light microscope with HE and PAS staining , especially in 4IH group.Masson staining showed no significant fibrotic response in the kidney of the rats exposed to IH .(2) The SOD levels in the serum and kid-ney were decreased after CIH .Compared with the corresponding control groups , the levels of serum SOD were significantly lower in CIH groups, especially in 4IH group.The mRNA expression of Cu/ZnSOD and MnSOD in CIH groups decreased significantly as compared with control groups .The mRNA levels of HIF-1αwere significantly higher in CIH groups than those in the corresponding control groups .CONCLUSION: CIH induces abnormalities of glomeruli and convoluted tu-bules, while 4-week IH exposure has not led to fibrotic response .CIH participates in the process of renal oxidative stress damage by upregulating HIF-1αtranscription and downregulating Cu/ZnSOD and MnSOD transcription .