| Research ObjectiveSleep apnea hypopnea syndrome is a clinical common sleep-related breathing disorder,it can lead to multiple systems comprehensive damage by means of some mechanisms. One of the most easily affected systems is cardiovascular system, SAHS combines with cardiovascular and cerebrovascular diseases can significantly increase mortality in patients.Chronic intermittent hypoxia is the characteristic performance in SAHS,studies show that CIH leading to the formation and development of atherosclerosis by inducing a series of pathophysiological changes in the body is the most important pathophysiological basis in SAHS combines with cardio-cerebrovascular disease.At present, the specific molecular mechanism of the formation of AS which CIH induced is not entirely clear.Previous studies have confirmed that the CIH can induce a variety of mechanisms to promote the formation and development of AS,this mechanisms may include oxidative stress and inflammation, neurohumoral regulation function disorder, endothelial dysfunction, high blood coagulation, and metabolic disorders.Thromboxane A2 is the main product of arachidonic acid metabolism,it is produced under the catalysis of cyclooxygenase-1 and thromboxane synthase. Because of the function of thromboxane A2 in promoting the platelet aggregation and release and vascular smooth muscle contraction,TXA2 plays an important role in the formation of atherosclerosis.the role of COX-1 pathways in the formation of atherosclerosis and thrombosis has been confirmed in a number of studies, but in the SAHS the role of COX-1 pathways in the formation of atherosclerosis is not clear,there is few research about this aspect at present.In the process of SAHS,CIH may promote the formation and development of atherosclerosis by activating COX-1 related metabolic pathways and increasing TXA2 synthesis.Therefore,in this study, we establish serious intermittent hypoxia rats model by imitating the human's SAHS in purpose of investigating the role of COX-1 pathways in the formation of atherosclerosis which induced by intermittent hypoxia,and providing the theoretical basis for prevention and treatment of cardiovascular complications. Experimental MethodEstablishing intermittent hypoxia rats model by imitating SAHS,32 healthy adult male Wistar rats were divided into four groups by random number table method,each grop had 8 rats. According to the experiment requirement, respectively seting up control group, high-fat group, intermittent hypoxia group,and high-fat combine with intermittent hypoxia group. During the period of modeling, the rats of control group were feed with ordinary fodder and accepted intermittent compressed air treatment for eight hours everyday, high-fat group were feed with high fat fodder and accepted intermittent compressed air treatment for eight hours everyday, intermittent hypoxia group were feed with ordinary fodder and accepted intermittent hypoxia dispose for eight hours everyday, high-fat combine with intermittent hypoxia group were feed with high fat fodder and accepted intermittent hypoxia dispose for eight hours everyday.At the end of the tenth week, all rats were put to death by femoral artery bleeding, blood samples were collected and the thoracic aorta tissue was separated from rats.Blood samples were used to test the level of serum lipid,pro-inflammatory cytokines and platelet activating factors.thoracic aorta tissue was used to observe the histopathological changes and test the level of COX-1 metabolic pathways relevant indicators COX-1 and TXS gene expression by RT-PCR. Experimental Result1.The effect of chronic intermittent hypoxia on the levels of serum proinflammatory cytokines in rats:The levels of serum TNF-? and IL-1 in high-fat combine with intermittent hypoxia group were significantly higher than control group, high-fat group and intermittent hypoxia group.2.The effect of chronic intermittent hypoxia on the levels of serum platelet activating factors in rats:The levels of serum PF4 in high-fat combine with intermittent hypoxia group were significantly higher than control group, high-fat group and intermittent hypoxia group.The levels of serum ?-TG in high fat group,intermittent hypoxia group and high-fat combine with intermittent hypoxia group were significantly elevated when compared with the control group, among the three grops,high-fat combine with intermittent hypoxia group increased more obviously.3.The effect of chronic intermittent hypoxia on the levels of COX-1 and TXS gene expression in Thoracic aorta tissue of rats:Compared with the control group,the levels of COX-1 mRNA and TXS mRNA expression in high fat group,intermittent hypoxia group and high-fat combine with intermittent hypoxia group were significantly elevated,high-fat combine with intermittent hypoxia group were significantly higher than the high fat group and intermittent hypoxia group.4. The changes of thoracic aorta tissue pathology on the effect of intermittent hypoxia in rats:Observed results using light microscope showed that the aorta of the blank control group was normal,vascular endothelium was complete and continuous, smooth muscle cell arranged orderliness.In the high fat group, intimal lipid deposition, foam cell infiltration, fatty streak formation, platelet and inflammatory cell accumulation,some shedded endothelial cells were observed.Incomplete endothelium,some shedded endothelial cells and nuclear debris,fatty streak formation were observed in intermittent hypoxia group.In the high-fat combine with intermittent hypoxia group,intimal lipid deposition,foam cell infiltration and fatty streak formation were observed,fibrinous thrombus formation can be found obviously.5.The bivariate correlation analysis results between platelet activation and COX- 1 pathway,PF4 and COX-1,PF4 and TXS, ?-TG and COX-1,?-TG and TXS were all had a positive correlation(P< 0.05). Conclusion1.Chronic intermittent hypoxia can induce vascular endothelial injury and early pathological changes of atherosclerosis.Especially on the basis of dyslipidemia,the endothelial injury is more serious.2.In the process of intermittent hypoxia inducing vascular endothelial injury,together with enhancement of inflammation response and platelet activation.3.Chronic intermittent hypoxia can activate COX-1 related metabolic pathways and increase the thromboxane A2 synthesis. Thromboxane A2 can lead to the activation of platelet.4. According to what had been said above,the activation of COX-1 pathway was the possible molecular mechanisms to promote the AS and thrombosis of severe SAHS model rats. |
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