Pyroptosis Mediated Renal Injury Caused By Chronic Intermittent Hypoxia In Rats And The Intervention Effect Of Edaravone

Objective: Sleep apnea hypopnea syndrome causes multi-system and multi-organ damage,which seriously threatens human physical and mental health.By making chronic intermittent hypoxia SD rats model,simulation of OSAHS patients at night sleep repeated hypoxia environment,To explore the role of cell pyroptosis in renal injury induced by chronic intermittent hypoxia in rats,at the same time edaravone was used as an intervention factor,to explore whether it can reduce kidney injury by blocking or inhibiting the pyroptosis-pathway,to provide a new method for prevention and treatment of systemic OSAHS damage.Methods: Twenty-four SPF male SD rats were randomly divided into normal control group（NC group）,intermittent hypoxia group（IH group）,intermittent hypoxia+ normal saline group（IH+NS group）and intermittent hypoxia + edaravone group（IH+EDA group）by random number table method,with 6 rats in each group.Rats in the IH group,IH+NS group and IH+EDA group were reared in intermittent hypoxia chamber for modeling for 8 hours a day.At the same time,rats in the IH+EDA group were intraperitoneally injected with edaravone injection according to the dose standard of 5mg/kg before modeling,while rats in the IH+NS group were intraperitoneally injected with normal saline according to the same dose standard to form a contrast.Total 8 weeks.After modeling,serum creatinine（Crea）and Urea（Urea）levels were measured;HE staining was used to observe the pathological morphological changes of the kidney under microscope;Masson staining was used to observe the degree of renal fibrosis;superoxide dismutase（SOD）activity and malondialdehyde（MDA）content were determined by chemical method.Immunohistochemistry was used to detect the expression levels of NLRP3,Caspase-1 and IL-1β related proteins in the pyroptosis pathway.Westernblot was used to detect the expression levels of Caspase-1 and IL-1β.The m RNA expression multiple of GSDMD and IL-18 in renal tissues was determined by real-time fluorescence quantitative polymerase chain reaction.Statistical software SPSS Statistics 25.0 was used for statistical analysis of the experimental data.Results:（1）The serum creatinine（Crea）and Urea（Urea）levels in intermittent hypoxia group and intermittent hypoxia + normal saline group were significantly higher than those in normal control group（P < 0.05）,but the levels of Crea and Urea in intermittent hypoxia + edaravone group were lower than those in intermittent hypoxia group（P <0.05）.（2）Intermittent hypoxia group,the intermittent hypoxia + saline group malpighian tube cavity appear distortion and the microscopic structure of disorder,individual lumen stenosis or occlusion,glomerular collagen fibers deposition/renal capsule balloon gap appeared,and intermittent hypoxia adr mentioned + group microscopically observed the pathological damage renal tubular relief,to improve the degree of fibrosis is not obvious;（3）The content of MDA in kidney tissue of intermittent hypoxia group and intermittent hypoxia + normal saline group was significantly increased compared with that of normal control group（P < 0.05）,the content of MDA in intermittent hypoxia +edaravone group was decreased compared with that of intermittent hypoxia group（P <0.05）,and the change trend of SOD activity was opposite（P < 0.05）.The results showed that intermittent hypoxia exposure caused disturbance of oxidation/antioxidant balance in vivo.（4）The expressions of NLRP3,Caspase-1,IL-1β,GSDMD m RNA and IL-18 m RNA in renal tissues of intermittent hypoxia group and intermittent hypoxia + normal saline group were significantly increased compared with that of normal control group（P < 0.05）.The above indexes in intermittent hypoxia + edaravone group were lower than those in intermittent hypoxia + edaravone group（P < 0.05）;Conclusions:（1）Chronic intermittent hypoxia stimulation can cause morphological and pathological damage and fibrosis of renal tissue,and renal function is damaged to a certain extent;（2）Chronic intermittent hypoxia can activate the classic pyroptosis signaling pathway of NLRP3/Caspase-1/GSDMD/IL-1β cells to mediate renal injury through oxidative stress;（3）Edaravone may inhibit the classical signaling pathway of pyroptosis by scavenging oxygen free radicals and down-regulating the oxidative stress level of the body,control the cascade of inflammatory response and reduce the degree of kidney injury.