养心生脉颗粒对异丙肾上腺素诱导的小鼠心肌缺血及焦虑样行为的影响

Effect of Yangxin Shengmai granules on myocardial ischemia and anxiety like behaviors induced by isoproterenol in mice

目的探究养心生脉颗粒对异丙肾上腺素(ISO)诱导的小鼠心肌缺血损伤的改善作用及焦虑样行为的影响。方法72只昆明小鼠随机分为空白组,模型组,养心生脉颗粒3.15、6.30、12.60 g·kg^(-1)组及阳性药组(复方丹参片0.432 g·kg^(-1)和地西泮0.001 g·kg^(-1)),连续灌胃给药8 d,除空白组外,其余各组小鼠于第5日给药30 min后,采用首次腹腔注射ISO(60 mg·kg^(-1)),第6~8日腹腔注射ISO(50 mg·kg^(-1))法制备小鼠心肌缺血模型,于第7日造模8 h后进行高架十字迷宫实验、明暗箱实验和旷场实验,于第8日灌胃给药1 h后,监测心电图0.5、5、10、15、20 min ST段的变化,取各组小鼠血清检测血清乳酸脱氢酶(LDH)、肌酸激酶(CK)水平。结果行为学结果显示,与空白组相比,模型组小鼠进入高架十字迷宫开放臂次数、滞留时间和旷场运动轨迹总路程均显著降低(P<0.01),在明暗箱中明箱停留的次数和时间以及进入旷场中心区域的次数和时间均明显减少,但差异无统计学意义;与模型组相比,养心生脉颗粒各给药组均可明显改善小鼠进入高架十字迷宫开放臂次数、滞留时间和旷场运动轨迹总路程(P<0.05,P<0.01),明箱停留的次数和时间以及进入旷场中心区域的次数和时间有升高的趋势,但效果均不显著。心电图及心肌酶谱结果显示,与模型组相比,养心生脉颗粒各给药组均能显著抑制ISO诱导的心电图ST段抬高以及血清心肌酶LDH、CK活力的升高(P<0.05,P<0.01)。结论养心生脉颗粒对ISO诱导小鼠心肌缺血损伤具有保护作用,并能够逆转其焦虑样行为。

Objective To determine the effect of Yangxin Shengmai granules on isoproterenol-induced myocardial ischemia and anxiety-like behaviors in mice.Methods Totally 72 KM mice were randomly divided into a blank group,a model group,3 Yangxin Shengmai granules groups at 3.15,6.30,and 12.60 g·kg^(-1) and a positive group(compound Danshen tablets 0.432 g·kg^(-1) and diazepam 0.001 g·kg^(-1)).The drug were given intragastrically for 8 days continuously.Except for the blank group,mice in the other groups were injected isoproterenol hydrochloride(ISO)(60 mg·kg^(-1))intraperitoneally 30 min after the administration on the 5th day,and ISO(50 mg·kg^(-1))intraperitoneally on the 6th-8th day.The elevated cross maze experiment,light-dark box test and open field experiment were conducted 8 h after the modeling on the 7th day.Electrocardiogram(ECG)was monitored for 0.5,5,10,15 and 20 min after the intragastric administration on the 8th day.The serum of the mice in each group was taken to detect the levels of serum lactate dehydrogenase(LDH)and creatine kinase(CK).Results The behavioral results showed that compared with the blank group,the number of open arms and residence time in the elevated cross maze,and the total distance in the open field of model group were significantly reduced(P<0.01).The number of staying in the light box and residence time in the light-dark box test and those of entering the central area of the open field were reduced,but without significance.Compared with the model group,each dose group of Yangxin Shengmai granules significantly improved the number of open arms and residence time in the elevated cross maze,and the total distance in the open field(P<0.05,P<0.01);the number and time of staying in the lignt box in the light-dark box test and those of entering the central area of open field tended to increase without significance.ECG and myocardial enzyme spectrum showed that compared with the model group,each dose group of Yangxin Shengmai granules significantly inhibited the elevation of ECG ST segment and increased the serum myocardial enzyme LDH and CK activities(P<0.05,P<0.01).Conclusion Yangxin Shengmai granules protect against ISO-induced myocardial ischemia in mice,and can reverse the anxiety-like behaviors.