| Background: obstructive sleep apnea hypopnea syndrome (OSAHS) is due to upper airway obstruction during sleep, leading to repeated hypoxia / reoxygenation, sleep disorders and other pathological processes. Recent studies have found that OSAHS can cause abnormal secretion of adipokines, however, its effect on adipocyte function. as well as the change of organ function and the exact mechanism is not clear.Objective: To study effects of OSAHS on plasma levels of adipocytokine resistin and adiponectin, and the relationship between the levels and patients with cardiovascular pathological degree , as well as CPAP treatment intervention, through the clinical observation of OSAHS patients. on the other hand, through establishment of rat model of intermittent hypoxia, to investigate the effect of intermittent hypoxia on oxidative stress, inflammation, lipid metabolism,adipocytokine secretion of rat to different diet . and observe expression level of resistin and adiponectin gene and protein in adipose, myocardi and vascular tissue, as well as expression of NF-kB and peroxisome proliferator activated receptor gamma (PPAR ?) gene in tissues, and to further understand the influence of oxidative stress in secretion of fat cells and the mechanism through the antioxidant glutathione (GSH) intervention.Methods: in the first part, 125 cases of OSAHS patients according to AHI were divided into mild group (30 cases), moderate group (29 cases) and severe group (35 cases), non-OSAHS obese 30 as over-weight group and normal weight 30 as healthy control group. The OSAHS group and obese group underwent polysomnography (PSG) before going to bed, blood pressure monitoring,plasma lipid, blood pressure, heart color ultrasound. All subjects for plasma resistin, adiponectin concentration detection, by enzyme linked immune method (ELISA). Plasma resistin and adiponectin concentration were repeated examination in line with the conditions of the 18 cases of moderate and severe OSAHS patients with CPAP treatment respectively after 1 month and 3 month. The second part: 48 male Sprague Dawley rats were randomly divided into 6 groups, each group of 8 rats, namely the ordinary diet control group (ODC), ordinary diet of intermittent hypoxia group (OD+IH). ordinary diet of intermittent hypoxia + glutathione intervention group(OD+IH+GSH), high fat diet group (HFC), high fat diet intermittent hypoxia group (HF+IH), high fat diet and intermittent hypoxia + glutathione intervention group (HF+IH+GSH). In the conditions of feeding after 4 weeks, blood, thoracic and abdominal aorta, adipose, cardiac tissue were taken to detect resistin and adiponectin, superoxide dismutase (SOD), malondialdehyde(MDA), glutathione peroxidase (GSH-XP), and inflammatory factor TNF- a, IL-6 in blood, as well as expression of resistin, adiponectin gene and protein, NF-kB mRNA and PPAR y mRNA in adipose, myocardium and vascular tissue. The ultrastructure of myocardium and vascular tissue were observed under transmission electron microscope.Results: in the first part, the resistin levels of plasma OSAHS was significantly higher than simple over-weight group (P <0.05) and control group (P < 0.01), and adiponectin levels was significantly lower than the obese group (P <0.05) and control group (P < 0.01). The resistin /adiponectin ratio in OSAHS group is significantly elevated to obese group and control group. The mean blood pressure in daytime, nighttime of OSAHS patients increased, and hypertension has a high proportion of 45.27%, and the non dipper blood pressure ratio were higher than that in simple obesity. There was more obvious dyslipidaemia (including TC, HDL, LDL) and Changes of left ventricular structure in OSAHS group. Correlation analysis showed, the plasma levels of resistin were negatively correlated with adiponectin. Resistin and adiponectin levels and their ratio was correlated with BMI, AHI sleep index, neck circumference, waist hip ratio, TC, blood pressure,left ventricular weight index. But only BMI, AHI, and TC had great contribution to the regression equation of resistin / Adiponectin ratio. The plasma concentration of resistin and adiponectin no significant changed in CPAP before and after 1month and 3 month treatment, while their ratio showed significant difference in 3 month treatment than before treatment. In the second part,both common diet or high fat diet rat, plasma SOD, GSH-PX activity decreased and MDA levels went up after 4 weeks intermittent hypoxia, and antioxidant intervention could significant increase SOD, GSH-PX concentration, and decreased MDA levels, but MDA changes had significant difference only in ordinary diet. IL-6 and TNF-a concentration in the rats after intermittent hypoxia exposure increased significantly, high fat diet group was more obvious, at the same time of antioxidant intervention both were reduced, and there was a significant difference only in the ordinary diet group. Plasma resistin levels was similar as previous two, whereas adiponectin was different. The level adiponectin in plasma significantly decreased after intermittent hypoxia, high fat diet group was more obvious, and antioxidant intervention could improve the abnormal in both of diet. Correlation analysis showed, resistin was positively associated with oxidative stress,inflammation and dyslipidemia, yet adiponectin was negatively associated with these pathological degrees. The mRNA and protein expression of resistin and adiponectin in three tissues was similar as their concentrations in the plasma, and the different case was the resistin had not significant change after antioxidant treatment in adipose tissue. Expression of NF- ? B P65 mRNA in intermittent hypoxia were significantly increased in three tissues , high fat diet group was remarkable, and decreased significantly in three tissues by glutathione intervention. PPAR ?mRNA in high fat diet group increased, while the expression of intermittent hypoxia is more obvious, but no significant difference in the same diet groups. The expression of NF- ? B P65 mRNA and PPAR ? mRNA were positively correlation with resistin mRNA, and negatively correlated with adiponectin mRNA. Electron microscope showed Intermittent hypoxia and high fat diet both could cause cell and tissue damage, function of intermittent hypoxia was more obvious, additive effects could even cause irreversible damage.Conclusion the first part: the increase of resistin and decrease of adiponectin of plasma concentration in OSAHS patients resulted in their ratio imbalance. This change was related with the extent of OSAHS, obesity, lipid metabolism disorders in patients with OSAHS. There were certain relations between the changes of resistin and adiponectin ratio and the average blood pressure, blood pressure circadian variation and left ventricular structure changes in patients with OSAHS. CPAP treatment could improve concentration changes of resistin and adiponectin in OSAHS patients to a certain extent, but the short-term effect was limited. The second part data shows,intermittent hypoxia could cause abnormal expression and secretion in resistin and adiponectin, through oxidative stress, inflammation and lipid metabolism disorders. If at the same time with high fat diet, intermittent hypoxia could strongly accelerate the consequence to further.That shows that intermittent hypoxia and high fat diet synergy role in the pathological process.The imbalance expression of inflammatory cytokines and anti-inflammatory cytokine prompted inflammation exists in adipose, cardiac, vascular tissue. Abnormal expression of adipokines in tissues by intermittent hypoxia may be related to the NF- ? B activation of P65 gene in response to oxidative stress and inflammation. One side, the lipid abnormalities may be the main reason for the high expression of PPAR ? mRNA in tissues, and intennittent hypoxia promotes the reaction process to a certain extent. On the other hand, abnormal expression of resistin and adiponectin may have a feedback effect on PPAR ? mRNA expression. Glutathione had certain intervention effect for adipose inflammatory reaction of though depressing oxidative stress. |
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