Effects Of Asphyxia On Cardiac β-adrenergic Receptor In Neonatal Mice

Objective: To investigate the effect of asphyxia on beta-adrenergic receptor（β-AR）in neonatal mice and the protective effect of β₂ agonist on immature cardiomyocytes.Methods: In part I,we randomly selected 36 mice 3 days after birth,6 mice were randomly selected from the mice at 3,5,7,14,21 and 28 days.The expressions of β₁ and β₂ receptors were detected by immunohistochemistry and western blotting.In part II,12 mice were divided into 2 groups randomly.The control group（CTL,n = 6）was placed in the jar only and no treatment.Asphyxia group（AS,n = 6）was treated with asphyxia of neonatal mice asphyxia model.Open the chest to remove the heart,the expression of β₁ and β₂ receptors in myocardium was detected by immunohistochemistry and western blotting.In part III,36 mice were divided into 3 groups randomly.CTL group（n = 12）only placed in the jar,do not do asphyxiation.AS group（n = 12）with the asphyxia model of the newborn mice asphyxia model.Fenoterol group（FEN,n = 12）2 hours before the asphyxia treatment was given Fenoterol,the remaining treatment is same with the AS group.The heart rate and left ventricular ejection fraction（LVEF%）were measured by cardiac ultrasonography at 3 days and 28 days.The expression of β₁ and β₂ receptors in myocardium was detected by immunohistochemistry and western blotting.Results:1.The expression of β₁-AR in the mice on the 3rd,5th,7th,14 th,21st and 28 th day of the CTL group increased gradually with the increase of the age.The expression of β₁-AR in the 28 th day was significantly higher than that in the 3-day mice（P < 0.05）;2.The expression of β₂-AR in the mice at the 3rd,5th,7th,14 th,21st and 28 th day of the CTL group decreased gradually with the increase of the age.The expression of β₂ receptor in the 28 th day was significantly lower than that in the 3-day mice（P < 0.05）;3.Compared with CTL group,the β₁ and β₂ receptors of myocardium in AS group were significantly decreased（P <0.05）;4.CTL group 3 days of normal mice myocardial cells arranged in neat,clear nucleus,cell membrane integrity,and no inflammatory cell exudation,myocardial edema and necrosis.AS group compared to mice 3 days in CTL group,heart rate increased（P <0.05）,LVEF% was significantly lower（P <0.05）.There was no significant difference in HW/BW（P> 0.05）,suggesting that myocardial injury;5.Compared with CTL group of mice 28 days,AS group HW / BW ratio increased,FEN group HW / BW ratio decreases,FEN group in contrast to AS group HW / BW reduced（P <0.05）;6.Compared with CTL group of mice 28 days,the heart rate of AS group was lower than that of CTL group,but there was no significant difference between the three groups（P> 0.05）.7.Compared with CTL group of mice 28 days,the LVEF% of FEN group and AS group were lower than CTL group（P <0.05）,FEN group LVEF% increased comparing AS group（P <0.05）;8.Compared with CTL group of mice 28 days,FEN group and AS group β₁,β₂-AR expression decreased,FEN group,compared to the AS group β₁-AR tended to increase,not statistically significant（P> 0.05）,FEN Group β₂-AR compared with AS group showed an increasing trend（P <0.05）.Conclusion:1.The expression of β₁ and β₂-AR in the normal mice can change with the age of the mice,and the expression of β₁-AR is up-regulated and the β₂-AR is down-regulated;2.Asphyxia 3 days mice showed heart rate increased,LVEF% decreased,suggesting that asphyxia can cause myocardial injury;3.Asphyxia caused by myocardial injury,the β₁,β₂-AR were significant decline4.Specific β₂-AR agonist Fenoterol treatment after the asphyxia mice compared with pure asphyxia mice,HW/BW get lower,LVEF% and β₂-AR increased,suggesting that Fenoterol can improve myocardial function,may be through the increase of β₂-AR.