Regulatory Effect Ofβ₂ Adrenergic Receptor On Ox-LDL Induced Pyroptosis Of HUVECs Cells

Background The prevalence and mortality of cardiovascular diseases in China are still on the rise.It is speculated that cardiovascular diseases will account for the main cause of death worldwide,which poses a serious threat to human health.Therefore,the occurrence mechanism and diagnosis and treatment of AS have correspondingly become the focus of research in recent years.Objective To observe the effect ofβ₂ adrenergic receptor on ox-LDL induced pyroptosis of HUVECs cells.Methods（1）HUVECs cells were used as the object of study.Detection of drug cytotoxicity by CCK8 method,to determine the optimal concentration of ox-LDL to damage HUVECs cells.Construction of a model of HUVECs cell pyroptosis;The cytotoxicity of the drug was detected by CCK8 method to determine the optimum concentration ofβ2adrenoceptor agonist（salbutamol hemisulfate）andβ2 adrenoceptor blocker（ICI11 8551）.（2）based on the pyroptosis model of HUVECs cells established by ox-LDL,Salbutamol semisulfate,ICI11 8551 and the combination of salbutamol semisulfate and ICI11 8551 were given respectively.（3）the contents of IL-18 and IL-1βin the supernatant of cells in each group were detected.（4）the content of LDH in the supernatant of each group was detected.（5）the expression levels of key proteins NLRP3,Caspase-1 and GSDMD in each group were detected by Western Blot.Results（1）CCK8 results showed that the survival rate of HUVECs cells decreased with the increase of ox-LDL,salbutamol hemisulfate and ICI11 8551 concentration,The cell survival rate was about 60%when the concentration of ox-LDL was 120μg/m L,and that of salbutamol and ICI11 8551 was about 80%when the concentration of salbutamol and ICI118551 was 10μmol/L.Therefore,the concentration of ox-LDL was 120μg/m L,and the concentration of salbutamol semisulfate and ICI118551 was 10μmol/L.（2）Western blot results showed that ox-LDL could promote the expression of NLRP3,Caspase-1,GSDMD,IL-18,IL-1βand promote the release of lactate dehydrogenase in HUVECs cells compared with the blank group.（3）Compared with ox-LDL group,β2 agonist salbutamol semisulfate promoted the expression of NLRP3,Caspase-1,GSDMD,IL-18 and IL-1β,and promoted the release of lactate dehydrogenase.β₂ receptor blocker ICI118 551 inhibited the expression of NLRP3,Caspase-1,GSDMD,IL-18,IL-1βand the release of lactate dehydrogenase.Conclusion Ox-LDL can induce pyroptosis of HUVECs cells.β₂ adrenergic receptor agonist salbutamol sisulfate promoted ox-LDL-induced pyroptosis of HUVECs cells,andβ₂blocker ICI118 551 inhibited ox-LDL induced pyroptosis of HUVECs cells.These results indicated thatβ2 adrenergic receptor could regulate ox-LDL induced pyroptosis of HUVECs cells,providing scientific basis for the application ofβ₂ receptor antagonist in clinical practice.