| Part One Establishment of a rat model of chronic intermittent hypoxia Objective: Chronic intermittent hypoxia is a characteristic manifestation in the pathogenesis of OSA,which is related to a variety of comorbidities in patients.In this study,We will simulate the pathogenesis of OSA and to establish a rat model of chronic intermittent hypoxia.Methods: Male SD(Sprague-Dawley)rats were randomly divided into normoxia control(NC)and chronic intermittent hypoxia(CIH)groups.The 9 CIH group rats were maintained from 00:00 to 17:00 and administered cyclic intermittent hypoxia treatment for 8 hours.Each hypoxia-reoxygenation cycle consisted of 30 seconds of hypoxia,rapid reoxygenation for 40 seconds,and 21% oxygen concentration treatment for 20 seconds.This procedure was repeated for 28 days.The NC group was administered a normoxia treatment.After modelling,the discharge signals of the hypoglossal nerve and genioglossus muscle of the two groups of rats were measured and compared.Results: After 4 weeks of modelling,the firing signals of the hypoglossal nerve and genioglossus muscle in the CIH group were significantly higher than those in the NC group and could be maintained for 60 minutes,thus showing long-term facilitation of the firing of the hypoglossal nerve and genioglossus muscle.Conclusion: After 4 weeks of CIH treatment,the discharge amplitudes of the hypoglossal nerve and genioglossus muscle in rats had significantly increased.These findings suggested that the normal pressure and chronic intermittent hypoxia environment that were used in this experiment could optimally simulate the pathogenesis of OSA.Part Two Effects of different hypoxic stimulations combined with electrical stimulations on the activity of the genioglossus muscle in chronic intermittent hypoxia-pretreated ratsObjective: To explore whether genioglossus discharge in chronic intermittent hypoxia(CIH)-pretreated rats can be enhanced by intermittent electrical stimulation combined with acute intermittent hypoxia(AIH).Methods: Rats were pretreated with CIH for 4 weeks and then randomly divided into the following 6 groups: time control,intermittent electric stimulation,AIH,intermittent electric stimulation+AIH,continuous electric stimulation,and continuous hypoxia exposure.The genioglossus discharges were recorded and compared both before and after stimulation.Normoxic-treated rats were grouped and treated with the same stimulation protocols.Results: Intermittent electrical stimulation or AIH temporarily increased genioglossus discharge,and the degree of the increase was significantly higher in CIH-pretreated rats than in normoxic rats.After intermittent electrical stimulation,AIH evoked a sustained elevation of genioglossus discharge activities in CIH-pretreated rats,in which the degree of the increase was significantly higher than that in the rats induced by a single intermittent electric stimulation.Conclusion: Intermittent electrical stimulation combined with AIH strengthens genioglossus plasticity in CIH-pretreated rats.Part Three Different hypoxic stimulations combined with electrical stimulation on the expression of plasticity-related proteins in the hypoglossal nuclei of rats with chronic intermittent hypoxic pretreatmentObjective: Respiratory plasticity has therapeutic significance for obstructive sleep apnoea(OSA).Plasticity can be induced through both electrical stimulation and intermittent hypoxia.However,there are few studies on the combination of the two methods to induce plasticity.The purpose of this study was to investigate the effects of electrical stimulation combined with acute intermittent hypoxia on the plasticity of the hypoglossal nucleus in rats preconditioned by chronic intermittent hypoxia.Methods: Adult male SD rats were treated with CIH for 4 consecutive weeks and then randomly divided into the following 6 groups: the CIH blank group,the intermittent electrical stimulation group,the AIH group,the AIH+intermittent electrical stimulation group,the continuous electrical stimulation group,and the continuous hypoxia group.The rats in the normoxia group were treated with normoxia for 4 weeks and then randomly divided into the following 6 groups: the normoxia blank group,the intermittent electrical stimulation group,the AIH group,the AIH+intermittent electrical stimulation group,the continuous electrical stimulation group,and the continuous hypoxia group.Each group was given the corresponding stimuli.After 10 days,the expression levels of plasticity-related molecules in the hypoglossal nerve nucleus of each group,as well as the levels of oxidative stress and inflammation,were measured.Results: Both AIH and intermittent electrical stimulation induced the expression of plasticity-related molecules in the hypoglossal nucleus of rats to different degrees and improved the ability of rats to resist CIH.Finally,the levels of oxidative stress and inflammation in rats were reduced to varying degrees.In the CIH pretreatment group,AIH combined with intermittent electrical stimulation increased the expression of plasticity-related molecules in the hypoglossal nucleus in rats and reduced the levels of oxidative stress and inflammation.The degrees of these change were greater than that caused by any single stimulation.Overall,continuous electrical stimulation and continuous hypoxic stimulation can induce the expression of plastic molecules in the hypoglossal nucleus and can aggravate the levels of oxidative stress and inflammation in the body.Conclusion: The results showed that intermittent electrical stimulation combined with intermittent hypoxic stimulation could further increase plasticity-related molecular expression in the hypoglossal nucleus of rats with chronic intermittent hypoxic pretreatment and can improve the resistance ability of rats to CIH,which demonstrates that the levels of inflammation and oxidative stress in vivo in CIH rats were reduced to varying degrees. |
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