Study On The Changes Of Inflammatory Response And Oxidative Stress In Patients With Obstructive Sleep Apnea Complicated With Hypertension

Preface:OS AS(obstructive sleep apnea syndrome)is a disease caused by sleep apnea,which causes hypoxemia and a series of clinical symptoms.CIH(chronic intermittent hypoxiaemia)is the key to the pathogenesis.In recent years,we have found that the prevalence of this disease is high and can cause many complications in other systems,of which cardiovascular disease is the most common.A large number of studies have found that inflammatory response and oxidative stress are important in the occurrence of OSAS with hypertension,and the development of OSAS plays an important role in stimulating systemic inflammation,oxidative stress,endothelial dysfunction and regular awakening lead to sympathetic nerve activation and other reactions,which can lead to high blood pressure.Current studies have shown that the state of CIH combined with hypertension in patients with OSAS may cause inflammatory responses in vivo,increase oxidative stress,and the levels of inflammatory cytokines and cytokines that mark oxidative stress,such as the level of NO,NOS,such as the proportion of interleukin-6(IL-6),TNF-a,CRP and so on.However,few studies have focused on the degree of inflammation and oxidative stress and the level of related factors in different populations.However,few studies have focused on the degree of inflammation and oxidative stress and the level of related factors in different populations.Hakka is a representative indigenous inhabitant in Guangzhou,because cultural traditions and eating habits are unique and regional,the study on the inflammatory and oxidative stress indexes of non-Hakka population can reflect the differences between different populations with the same disease in the same region.So animal experiments are indispensable.We simulate the process of hypertension induced by CIH in rats,and by detecting the levels of inflammatory factors and some markers of oxidative stress in the experimental and control groups,To study the degree of inflammatory response and oxidative stress,and further study at the cell level to draw a conclusion.Part I.Study on the changes of inflammatory response and oxidative stress in patients with obstructive sleep apnea complicated with hypertensionBackground and purpose:With the development of medicine,some studies have found that the prevalence of OSAS with hypertension in recent years is higher than that in previous years.At present,there are few studies on inflammatory reaction and oxidative stress response in different groups of people suffering from OSAS and hypertension.In view of Hakka people’s unique lifestyle and eating habits,they are geographically representative.It can reflect the difference between different groups of people with the same disease in the same area.Through the comparison of clinical data,inflammatory factors and oxidative stress factors between Hakka and non-Hakka people,the difference of inflammatory response and oxidative stress response in OSAS patients with hypertension was studied.Monitoring the level of inflammatory factors can provide an effective way to evaluate the severity and prognosis of patients with hypertension and provide a theoretical basis for the prevention and treatment of OSAS with hypertension.Method:The serum levels of IL-6 TNF-α CRP and NO NOS in patients with hypertension in Hakka and non-Hakka population were determined by ELISA method,and the results were obtained by statistical method.Results:The average SAP of non-Hakka group was higher than that of Hakka group(P<0.05),but the average levels of map and HR were not significantly different from those of Hakka group.The average serum levels of IL-6 and TNF-α in non-Hakka patients were higher than those in Hakka patients(P<0.05),while the average serum levels of CRP were slightly higher than those of Hakka patients(P<0.05).The average level of serum no in non-Hakka patients was significantly lower than that in Hakka population.The difference was statistically significant(P<0.05),but the average level of serum NOS was slightly lower than that of Hakka population,but the difference was not statistically significant.Conclusion:In the non-Hakka population,the SAP of the patients with OSAS and hypertension was relatively high,while the SAP of the patients with hypertension in Hakka population was relatively low,which may be related to the healthy lifestyle of Hakka people and the unique diet culture.The level of inflammatory factors and the index representing oxidative stress level directly reflect the severity of inflammation and oxidative stress,which indicates that non-Hakka patients suffer from OSAS with hypertension.Inflammatory responses and oxidative stress were more severe in vivo than in Hakka patients.However,the correlation between the two responses and cytokines needs to be verified by the second part of the experiment.Part Ⅱ.Study on the relationship between chronic intermittent hypoxia induced Hypertension and inflammatory response and oxidative stress in RatsBackground and purpose:The CIH state of OSAS patients can induce inflammation,oxidative stress,endothelial function damage and so on to make the patients suffer from hypertension at the same time,so the inflammatory response and oxidative stress reaction will also be increased compared with the normal control group.The correlation between the two responses and cytokines is also an aspect of this study.Animal experiments are indispensable.Through the establishment of animal model,the levels of blood pressure,heart rate,inflammatory factors and oxidative stress factors in rats were measured to explore the changes of the above indexes after CIH induction.The correlation between the severity of inflammatory reaction and the level of inflammatory factors and the degree of oxidative stress and the level of related factors of oxidative stress provides a theoretical basis for the clinical study of the pathogenesis of OSAS with hypertension.Method:The CIH induced hypertension model was established in rats.The levels of IL-6 TNF-a CRP and NO NOS in serum of rats in CIH group and control group were detected by ELISA method,and the results were obtained by statistical method.Results:The levels of heart rate,blood pressure,inflammatory factor IL-6 TNF-a and CRP in CIH group were significantly higher than those in control group(P<0.05),while the growth rate of body weight,the levels of no and NOS related to oxidative stress response were lower than those in control group.The difference was statistically significant(P<0.05).The levels of IL-6 TNF-a and CRP were positively correlated with blood pressure and heart rate,while NO NOS was negatively correlated with blood pressure and heart rate.Conclusion:The induction of CIH can slow down the growth rate of rat body weight,induce hypertension in rats,and induce the increase of inflammatory response and oxidative stress in rats.There was a positive correlation between inflammatory response and inflammatory factors,and a negative correlation between oxidative stress and the level of NO NOS,and the inflammatory response and oxidative stress reaction in rats gradually increased with the prolongation of the course of disease.Part Ⅲ.Changes of Lymphocyte inflammation and oxidative stress in hypertensive Rats induced by chronic intermittent hypoxiaBackground and purpose:OSAS is closely associated with cardiovascular disease,and OSAS is an independent risk factor for cardiovascular disease.It is known from the literature that lymphocytes are related to various immune stress reactions.In previous animal experiments,the presence of a large number of lymphocytes and monocytes activation was also confirmed in hypertensive rats.In this study,CIH was isolated to induce lymphocytes in hypertensive rats and control rats,and the levels of no and iNOS in lymphocytes were detected and compared.To investigate the effect of CIH induced hypertension on the levels of lymphocyte inflammatory response and oxidative stress in rats.Method:Lymphocytes were extracted from the rat model of hypertension induced by CIH in the second part,and the levels of IL-6 TNF-a CRP and NO iNOS were detected by WB method.The results were obtained by statistical method.Results:The activity and purity of lymphocytes in the CIH group were generally lower than those in the control group,and the apoptosis degree was significantly higher than that in the control group(P<0.05).The levels of IL-6 TNF-a CRP iNOS and NO in the lymphocytes of the control group were significantly higher than those in the control group(P<0.05).Conclution:The state of CIH not only can induce hypertension in rats,but also reduce the activity and purity of lymphocytes,and can improve the apoptosis of lymphocytes in CIH group.It can increase the intensity of inflammatory reaction and oxidative stress reaction in lymphocytes.Part Ⅳ.Changes of vascular endothelial cell inflammation and oxidative stress in hypertensive rats induced by chronic intermittent hypoxia and their correlation with lymphocytic inflammation and oxidative stressBackground and purpose:The induction of CIH can promote the interaction between vascular endothelial cells and inflammatory cells in patients with OSAS.Vascular endothelial cells are the target cells of inflammatory related factors and also the target cells of lymphocyte toxicity attack.By detecting the levels of IL-6 TNF-a CRP and NO iNOS eNOS in vascular endothelial cells of hypertensive rats induced by CIH,the degree of inflammatory response and oxidative stress in vascular endothelial cells under CIH condition was studied,and the degree of co-culture of lymphocytes and endothelial cells in rats was studied.To investigate the effect of lymphocytes on the inflammatory response and oxidative stress of endothelial cells.Method:The lymphocytes and endothelial cells extracted from the second part of the control group were induced by CIH for different time.The levels of IL-6 TNF-a CRP and NO NOS in the endothelial cells induced by CIH were measured by WB method,and then the lymphocytes were treated with normoxia.Endothelial cells were co-cultured and the levels of IL-6 TNF-a CRP and NO iNOS eNOS in the culture medium were detected by ELISA method.The results were obtained by statistical method.Results:When the endothelial cells were in the CIH environment,the inflamm-atory cytokines IL-6,TNF-αand CRP in the cells increased,and the levels of NO and eNOS decreased.When the lymphocytes of CIH rats were co-cultured with CIH rat endothelial cells,the inflammatory response-related factors IL-6 TNF-a and CRP increased in the supernatant,while the levels of NO and NOS related to oxidat-ive stress were decreased.Conclution:The degree of inflammatory response and oxidative stress of endothelial cells induced by CIH increased,and the inflammatory response and oxidative stress reaction of lymphocytes and endothelial cells in rats induced by CIH could interact with each other.