Possible Mechanism Of Myocardial Fibrosis Induced By Intermittent Hypoxia In ApoE^-/- Mice

PurposeAt present,cardiovascular disease is one of the most serious diseases that affect human health.Myocardial fibrosis is a common pathological manifestation of many cardiovascular diseases.A large number of studies have shown that intermittent hypoxia?IH?can promote the occurrence of myocardial fibrosis.Whether the TLR4/NF-?B pathway is related to the occurrence of myocardial fibrosis induced by IH is relatively rare reported.Based on these backgrounds,we hypothesized that the TLR4/NF-?B pathway may play a key role in the development of IH-induced myocardial fibrosis.This experiment was designed to explore the role of TLR4/NF-?B pathway in the development of myocardial fibrosis induced by IH.The main feature of obstructive sleep apnea?OSA?is IH.Therefore,we used apolipoprotein E deficient?apoE-/-?mice as carriers of OSA to construct OSA animals.In the model,the role of TLR4/NF-?B in the development of myocardial fibrosis was observed by detecting the expression of the corresponding factors,and the expression of inflammatory factors in the myocardial tissue.So as to provide a new insight for the prevention and treatment of clinical OSA with myocardial fibrosis.Methods1.Animal experiment grouping and treatmentTwelve 8-week-old apolipoprotein E knockout?apoE-/-?male C57BL/6background mice were randomly divided into sham intermittent hypoxia group?n=6??HFD?and intermittent hypoxia group?n=6??IH?.The intermittent hypoxia group was treated with hypoxia for 6 hours after 6 hours of hypoxia,and the hypoxic hypoxic group was placed in the same environment but the oxygen content was normal.The two groups of mice were placed in the same environment for hypoxia reoxygenation or hypoxic reoxygenation for 5 weeks.The period of intermittent hypoxia was selected from 8:00 am to 17:00 pm,because this time coincided with the sleep time of the mice,and the hypoxic treatment during this period was the closest to the pathogenesis of OSA.2.Pathological examinationThe paraffin sections of the two groups of myocardium were treated with immunohistochemical staining to detect the content of TLR4,NF-?B,IL-6,TNF-?.Sirius red staining and masson staining were used to observe the degree of myocardial fibrosis.HE staining was used to observe the cell morphology.Results1.The content of collagen fibers in IH group was higher than that in HFD group;2.The expression of TLR4 protein in myocardial cytoplasm was higher in IH group than in HFD group?p<0.01?;3.The expression of NF-?B protein in myocardial cytoplasm of IH mice was higher than that of HFD group,and the difference was statistically significant?p<0.01?;4.The expression of IL-6 protein in myocardial cytoplasm of IH mice was higher than that of HFD group,and the difference was statistically significant?p<0.01?;5.The expression of TNF-?protein in myocardial cytoplasm of IH mice was higher than that of HFD group,and the difference was statistically significant?p<0.01?.Conclusions1.IH exposure induced myocardial fibrosis in ApoE^-/-mice.2.One of the mechanisms of myocardial fibrosis induced by IH may be the activation of TLR4/NF-?B pro-inflammatory signaling pathway.