The Damage Of Intermittent Hypoxia To Myocardium And The Expression Of TLR-4 In Myocardium

Objective Chronic intermittent hypoxia is the main pathophysiological feature of obstructive sleep apnea hypopnea syndrome(OSAHS),and it is also an important cause of long-term chronic inflammatory response of multiple systems in human body.Toll like receptor-4(TLR-4)is an important protein involved in non-specific immunity,which is also plays an important role in human inflammatory response.We established a model of intermittent hypoxia to simulate the occurrence of OSAHS,so as to study the effect of intermittent hypoxia on myocardial injury,and to explore the expression and clinical significance of TLR-4 in myocardial tissue of rats with intermittent hypoxia,to provide new diagnosis and treatment basis and research for clinical prevention and treatment of OSAHS related cardiovascular diseases train of thought.Methods We randomly divided 32 healthy male Wistar rats into 4 groups,8 rats in each group.Following is the grouping method : 1.Normal control group: rats live in a normal oxygen environment and can move freely;2.Mild hypoxia group: rats live in intermittent hypoxia chamber,resulting in intermittent hypoxia model with oxygen concentration of 15%;3.Moderate hypoxia group: rats live in intermittent hypoxia chamber,resulting in intermittent hypoxia model with oxygen concentration of 9%;4.Severe hypoxia group: rats live in intermittent hypoxia chamber,resulting in intermittent hypoxia model with oxygen concentration of 6%.All rats were killed after 5 weeks of continuous modeling for 8 hours every day.We took the heart tissue of rats,to observe the changes of heart tissue morphology by electron microscope after hematoxylin eosin staining,and to observe the expression of TLR-4 in the heart tissue of rats with different degrees of intermittent hypoxia by immunohistochemistry.Results 1.Compared with the normal control group,the myocardial tissue in the mild hypoxia group showed some disorder in the course of myocardial tissue,but the size and arrangement of nuclei were still relatively regular.In the moderate hypoxia group,the myocardial tissue was arranged in a "wavy" pattern,with different sizes of nuclei,disordered arrangement and enlarged myocardial space.The arrangement of myocardium in severe hypoxia group was more irregular than that in moderate hypoxia group,the myocardial space was enlarged,some myocardium was broken,some myocardial cells were denatured and necrotic.2.The expression of TLR-4 in the membrane and cytoplasm of macrophages in normal heart tissue was observed under light microscope.In addition to macrophages,TLR-4 positive signal was expressed in the cytoplasm and the surface of cell membrane in the cardiac tissue of rats in intermittent hypoxia group.The color of TLR-4 positive signal was brown yellow or brown.The results of image analysis showed that compared with the normal control group,TLR-4 expression level in mild hypoxia group,moderate hypoxia group and severe hypoxia group increased significantly(P < 0.05).Conclusion 1.Our study shows that the myocardium of rats is damaged in the intermittent hypoxia environment,and the degree of myocardial damage is also increased with the aggravation of the degree of intermittent hypoxia;2.the expression of TLR-4 in the myocardium of rats increases with the aggravation of the degree of intermittent hypoxia,and the inflammatory signal pathway mediated by TLR-4 may further lead to myocardial damage;3.We hope to provide some reference for TLR-4 as a valuable target of prevention and treatment of cardiovascular diseases related to OSAHS through this experiment.