依达拉奉对心搏骤停大鼠心肌保护作用及水通道蛋白4、水通道蛋白9的作用
|
摘要
目的分析依达拉奉对水通道蛋白4(AQP4)、水通道蛋白9(AQP9)表达的影响,探讨依达拉奉对心搏骤停(CA)大鼠心肌保护作用机制。方法选取96只健康SD大鼠,将其采用随机数字表法分为假手术组(28例),依达拉奉组(34例)、生理盐水组(34例),依达拉奉组及生理盐水组诱导建立CA模型,模型建立5 min后开始进行心肺复苏(CPR),待自主循环恢复后,依达拉奉组立即静脉注射3 mg/mL依达拉奉,生理盐水组给予等体积生理盐水,假手术组不诱导CA模型,仅进行动、静脉置管及气管插管。连续监测三组心电图及血流动力学1 h后缝合伤口,待模型大鼠苏醒后拔除插管,放入笼中常规饲养。分别于自主循环恢复后12、24、48、72 h处死大鼠,测定三组心肌组织中超氧化物歧化酶(SOD)、丙二醛(MDA)水平,光学显微镜下观察不同时间点心肌病理学变化、测定脑组织含水量,采用实时荧光定量聚合酶链式反应(RT-PCR)检测脑组织AQP4、AQP9 mRNA水平。结果三组大鼠体质量、平均动脉压、舒张压、收缩压及心率等基础参数比较,均差异无统计学意义(P>0.05);12、24、48、72 h处死大鼠,假手术组心肌组织中SOD水平均明显高于依达拉奉组、生理盐水组,差异有统计学意义(P<0.05),MDA水平明显低于依达拉奉组及生理盐水组(P<0.05);依达拉奉组12、24、48、72 h心肌组织中SOD水平分别为[(76.54±9.03)、(66.53±8.25)、(57.21±7.82)、(67.02±8.47)U/mg]均明显高于生理盐水组(P<0.05),依达拉奉组12、24、48、72 h心肌组织中MDA水平[(11.36±1.15)、(18.29±2.96)、(23.07±2.37)、(20.83±1.82)nmol/mg]明显低于生理盐水组(P<0.05);各时间点生理盐水组心肌病理学损伤程度均高于依达拉奉组;12、24、48、72 h处死大鼠,依达拉奉组脑组织含水量[(74.36±7.41)、(74.51±7.31)、(75.32±7.25)、(74.23±7.14)%]均明显低于生理盐水组(P<0.05),依达拉奉组AQP4水平分别为[(1.21±0.11)、(1.13±0.12)、(0.87±0.10)、(0.79±0.11)]明显低于生理盐水组(P<0.05);依达拉奉组AQP9 mRNA水平分别为[(0.82±0.14)、(0.70±0.11)、(0.62±0.12)、(0.50±0.11)]均明显低于生理盐水组(P<0.05)。结论依达拉奉可减轻CA大鼠CPR后心肌损伤,可通过下调AQP4、AQP9表达减轻大鼠脑水肿。
Objective To analyze the effects of edaravone on the expression of aquaporin 4(AQP4) and aquaporin 9(AQP9),and to explore the mechanism of edaravone on myocardium protective in rats with cardiac arrest(CA).Methods Ninety-six healthy SD rats were selected and randomly assigned into sham operation group(28 cases),edaravone group(34 cases),and saline group(34 cases).Edaravone group and saline group were induced to establish CA models,and cardiopulmonary resuscitation(CPR) was started at 5 minutes after the establishment of the model,after the recovery of autonomic circulation,the edaravone group was injected with 3 mg/mL edaravone intravenously immediately,the saline group was given the same volume of saline,the sham operation group did not induce CA model,but only underwent arterial catheterization,venous catheterization,and tracheal intubation.The electrocardiogram and hemodynamics were continuously monitored in three groups,after 1 hour,the wound was sutured,and the intubation was pulled out after the model rats awakened,and the rats were put into the cage for routine feeding.The rats were sacrificed at 12,24,48,and 72 hours after the recovery of autonomic circulation,the levels of superoxide dismutase(SOD) and malondialdehyde(MDA) in myocardium of three groups were measured,the myocardial pathological changes at different time points were observed under optical microscope,and water content in brain tissues was measured,real-time fluorescence quantitative polymerase chain reaction(RT-PCR) was used to detect the levels of AQP4 and AQP9 in brain tissues.Results There were no significant differences in basic parameters such as body mass,mean arterial pressure,diastolic pressure,systolic pressure,and heart rate among the three groups(all P > 0.05);the rats were killed at 12 h,24 h,48 h,and 72 h,the level of SOD in myocardial tissues in sham-operated group was significantly higher than that in edaravone group and saline group(P<0.05),MDA level was significantly lower than that in edaravone group and saline group(P<0.05);the level of SOD in myocardial tissues of edaravone group at 12 h,24 h,48 h,and 72 h was(76.54±9.03)U/mg,(66.53±8.25)U/mg,(57.21±7.82)U/mg,and(67.02±8.47)U/mg,respectively,which was significantly higher than that of saline group(P<0.05);the level of MDA in myocardial tissues of edaravone group at 12 h,24 h,48 h,and 72 h was(11.36±1.15)nmol/mg,(18.29±2.96)nmol/mg,(23.07±2.37)nmol/mg,and(20.83±1.82)nmol/mg,respectively,which was significantly lower than that of saline group(P<0.05);the degree of myocardial pathological injury in saline group was higher than that in edaravone group at each time point;the rats were killed at 12 h,24 h,48 h,and 72 h,the water content in brain tissues of edaravone group was(74.36±7.41)%,(74.51±7.31)%,(75.32±7.25)%,and(74.23±7.14)%,respectively,which was significantly lower than that in saline group(P<0.05);AQP4 level in edaravone group was(1.21±0.11),(1.13±0.12),(0.87±0.10),and(0.79±0.11),respectively,which was significantly lower than that in saline group(P<0.05);AQP9 mRNA level in edaravone group was(0.82±0.14),(0.70±0.11),(0.62±0.12),(0.50±0.11),respectively,which was significantly lower than that in saline group(P<0.05).Conclusion Edaravone can alleviate myocardial injury after CPR in CA rats,and reduce brain edema by down-regulating the expressions of AQP4 and AQP9.
Objective To analyze the effects of edaravone on the expression of aquaporin 4(AQP4) and aquaporin 9(AQP9),and to explore the mechanism of edaravone on myocardium protective in rats with cardiac arrest(CA).Methods Ninety-six healthy SD rats were selected and randomly assigned into sham operation group(28 cases),edaravone group(34 cases),and saline group(34 cases).Edaravone group and saline group were induced to establish CA models,and cardiopulmonary resuscitation(CPR) was started at 5 minutes after the establishment of the model,after the recovery of autonomic circulation,the edaravone group was injected with 3 mg/mL edaravone intravenously immediately,the saline group was given the same volume of saline,the sham operation group did not induce CA model,but only underwent arterial catheterization,venous catheterization,and tracheal intubation.The electrocardiogram and hemodynamics were continuously monitored in three groups,after 1 hour,the wound was sutured,and the intubation was pulled out after the model rats awakened,and the rats were put into the cage for routine feeding.The rats were sacrificed at 12,24,48,and 72 hours after the recovery of autonomic circulation,the levels of superoxide dismutase(SOD) and malondialdehyde(MDA) in myocardium of three groups were measured,the myocardial pathological changes at different time points were observed under optical microscope,and water content in brain tissues was measured,real-time fluorescence quantitative polymerase chain reaction(RT-PCR) was used to detect the levels of AQP4 and AQP9 in brain tissues.Results There were no significant differences in basic parameters such as body mass,mean arterial pressure,diastolic pressure,systolic pressure,and heart rate among the three groups(all P > 0.05);the rats were killed at 12 h,24 h,48 h,and 72 h,the level of SOD in myocardial tissues in sham-operated group was significantly higher than that in edaravone group and saline group(P<0.05),MDA level was significantly lower than that in edaravone group and saline group(P<0.05);the level of SOD in myocardial tissues of edaravone group at 12 h,24 h,48 h,and 72 h was(76.54±9.03)U/mg,(66.53±8.25)U/mg,(57.21±7.82)U/mg,and(67.02±8.47)U/mg,respectively,which was significantly higher than that of saline group(P<0.05);the level of MDA in myocardial tissues of edaravone group at 12 h,24 h,48 h,and 72 h was(11.36±1.15)nmol/mg,(18.29±2.96)nmol/mg,(23.07±2.37)nmol/mg,and(20.83±1.82)nmol/mg,respectively,which was significantly lower than that of saline group(P<0.05);the degree of myocardial pathological injury in saline group was higher than that in edaravone group at each time point;the rats were killed at 12 h,24 h,48 h,and 72 h,the water content in brain tissues of edaravone group was(74.36±7.41)%,(74.51±7.31)%,(75.32±7.25)%,and(74.23±7.14)%,respectively,which was significantly lower than that in saline group(P<0.05);AQP4 level in edaravone group was(1.21±0.11),(1.13±0.12),(0.87±0.10),and(0.79±0.11),respectively,which was significantly lower than that in saline group(P<0.05);AQP9 mRNA level in edaravone group was(0.82±0.14),(0.70±0.11),(0.62±0.12),(0.50±0.11),respectively,which was significantly lower than that in saline group(P<0.05).Conclusion Edaravone can alleviate myocardial injury after CPR in CA rats,and reduce brain edema by down-regulating the expressions of AQP4 and AQP9.
引文
[1] 林书生,蒋福初,赵开萌,等.ICU内心脏骤停患者心肺脑复苏结果分析[J].江苏医药,2016,42(12):1395-1396.
[2] 陈志刚,吴敏,邱晨,等.院前救治596例心脏骤停患者特点分析[J].灾害医学与救援:电子版,2016,5(1):16-19.
[3] 章森苗,黄坚强,汪春燕.不同心肺复苏方法对院前急救心脏骤停患者预后的影响[J].现代实用医学,2015,27(3):321-322.
[4] BHANJI F,DONOGHUE AJ,WOLFF MS,et al.Part 14: Education: 2015 American heart association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care[J].Circulation,2015,132(18 Suppl 2):S561-S573.
[5] 苏晓,陈蒙华,林松,等.影响心脏骤停患者心肺复苏成功率的因素分析[J].现代生物医学进展,2016,16(25):4916-4918.
[6] 张栋益,康深松.氧自由基与皮瓣缺血再灌注损伤[J].中华实用诊断与治疗杂志,2014,28(4):317-319.
[7] 邝桐博,皋聪,季晖.自由基清除剂依达拉奉的药理作用研究进展[J].安徽医药,2014,18(5):804-808.
[8] 靳伟.依达拉奉联用阿加曲班治疗急性脑梗死的临床疗效观察[J].安徽医药,2016,20(8):1579-1581.
[9] 王欣,施蝉宏,毛蓉嫣.依达拉奉对老年短暂性脑缺血发作患者血清超氧化物歧化酶和丙二醛的影响[J].中华老年医学杂志,2015,34(12):1310-1312.
[10] 李瑜,杨浩军.依达拉奉对 COPD 急性加重患者血清性介质、氧化应激及肺功能的影响[J].湖南师范大学学报:医学版,2016,13(2):42-45.
[11] 夏长伟.依达拉奉在心血管疾病中应用研究进展[J].中华实用诊断与治疗杂志,2016,30(4):328-330.
[12] 董静,褚鹤龄,高子丹,等.水通道蛋白4与脑血管病[J].国际脑血管病杂志,2016,24(11):1050-1054.
[13] 夏文政,胡韶山.水通道蛋白4与脑水肿研究进展[J].现代生物医学进展,2015,15(4):768-770.
[14] 赵静,陈忠云,杜继臣,等.水通道蛋白9与血脑屏障通透性在大鼠缺血性脑水肿中的变化[J].神经损伤与功能重建,2013,8(1):7-11.
[15] 姜广宇,董航,顾志成,等.自发性蛛网膜下出血大鼠脑水肿与水通道蛋白-9的表达[J].黑龙江医药科学,2016,39(4):75-76.
[2] 陈志刚,吴敏,邱晨,等.院前救治596例心脏骤停患者特点分析[J].灾害医学与救援:电子版,2016,5(1):16-19.
[3] 章森苗,黄坚强,汪春燕.不同心肺复苏方法对院前急救心脏骤停患者预后的影响[J].现代实用医学,2015,27(3):321-322.
[4] BHANJI F,DONOGHUE AJ,WOLFF MS,et al.Part 14: Education: 2015 American heart association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care[J].Circulation,2015,132(18 Suppl 2):S561-S573.
[5] 苏晓,陈蒙华,林松,等.影响心脏骤停患者心肺复苏成功率的因素分析[J].现代生物医学进展,2016,16(25):4916-4918.
[6] 张栋益,康深松.氧自由基与皮瓣缺血再灌注损伤[J].中华实用诊断与治疗杂志,2014,28(4):317-319.
[7] 邝桐博,皋聪,季晖.自由基清除剂依达拉奉的药理作用研究进展[J].安徽医药,2014,18(5):804-808.
[8] 靳伟.依达拉奉联用阿加曲班治疗急性脑梗死的临床疗效观察[J].安徽医药,2016,20(8):1579-1581.
[9] 王欣,施蝉宏,毛蓉嫣.依达拉奉对老年短暂性脑缺血发作患者血清超氧化物歧化酶和丙二醛的影响[J].中华老年医学杂志,2015,34(12):1310-1312.
[10] 李瑜,杨浩军.依达拉奉对 COPD 急性加重患者血清性介质、氧化应激及肺功能的影响[J].湖南师范大学学报:医学版,2016,13(2):42-45.
[11] 夏长伟.依达拉奉在心血管疾病中应用研究进展[J].中华实用诊断与治疗杂志,2016,30(4):328-330.
[12] 董静,褚鹤龄,高子丹,等.水通道蛋白4与脑血管病[J].国际脑血管病杂志,2016,24(11):1050-1054.
[13] 夏文政,胡韶山.水通道蛋白4与脑水肿研究进展[J].现代生物医学进展,2015,15(4):768-770.
[14] 赵静,陈忠云,杜继臣,等.水通道蛋白9与血脑屏障通透性在大鼠缺血性脑水肿中的变化[J].神经损伤与功能重建,2013,8(1):7-11.
[15] 姜广宇,董航,顾志成,等.自发性蛛网膜下出血大鼠脑水肿与水通道蛋白-9的表达[J].黑龙江医药科学,2016,39(4):75-76.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |