Role of angiotensin H type 2 receptor in repeated propofol anesthesia-induced neuroapoptosis in hippocampus of newborn rats / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of the angiotensin Ⅱ type 2 receptor (AT2R) in repeated propofol anesthesia-induced neuroapoptosis in the hippocampus of newborn rats.Methods Fiftyfour pathogen-free Sprague-Dawley rats,aged 7 days,weighing 10-15 g,were divided into 3 groups (n=18 each) using a random number tablecontrol group (group C),repeated propofol anesthesia group (group P) and AT2R agouist CGP42112A group (group G).In group C,0.9％ sodium chloride injection 3 ml/kg was intraperitoneally injected,and half of the initial dose 1.5 ml/kg was given every 20 min for 5 times in total,lasting for 3 consecutive days.In group P,propofol 30 mg/kg was intraperitoneally injected,and half of the initial dose 15 mg/kg was given every 20 min for 5 times in total,lasting for 3 consecutive days.In group G,a single bolus of CGP42112A 1 mg/kg was intraperitoneally injected,propofol 30 mg/kg was intraperitoneally injected 5 min later,and half of the initial dose of propofol 15 mg/kg was given every 20 min for 5 times in total,lasting for 3 consecutive days.At 2 h after emergence from anesthesia,6 rats were sacrificed and brains were removed for detection of neuroapoptosis in the hippocampus by TUNEL assay.The apoptosis index was calculated.Another 6 rats were sacrificed,brains were removed and hippocampi were isolated for determination of the expression of activated caspase-3,AT2R and peroxisome proliferator-activated receptor gamma (PPARγ) in hippocampal tissues by Western blot.The other 6 rats were fed until 28 days old,and the cognitive function was then assessed using Morris water maze test.Results Compared with group C,the escape latency was significantly prolonged,the time of staying at the target quadrant was shortened,the frequency of crossing the platform was decreased,the apoptosis index was increased,the expression of activated caspase-3 was up-regulated,and the expression of AT2R and PPARγ was down-regulated in group P (P＜0.05),and no significant change was found in the parameters mentioned above in group G (P＞0.05).Compared with group P,the escape latency was significantly shortened.the time of staying at the target quadrant was prolonged,the frequency of crossing the platform was increased,the apoptosis index was decreased,the expression of activated caspase-3 was down-regulated,and the expression of AT2R and PPARγ was up-regulated in group G (P＜0.05).Conclusion Inhibited activity of AT2R is involved in repeated propofol anesthesia-induced neuroapoptosis in the hippocampus of newborn rats.