对乙酰氨基酚对早产幼鼠模型血流动力学、左心室功能和血浆脑钠肽水平的影响
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摘要
目的:探讨对乙酰氨基酚对早产幼鼠血流动力学、左心室功能和血浆脑钠肽(BNP)水平的影响,阐明其治疗早产儿动脉导管未闭(PDA)的作用机制。方法:孕鼠腹腔注射脂多糖(LPS)制备早产幼鼠模型,早产幼鼠分为模型对照组(n=18)和给药组(n=19),另选10只足胎龄幼鼠作为空白对照组。空白对照组幼鼠不做任何处理,模型对照组幼鼠不给药,给药组幼鼠连续3d给予对乙酰氨基酚。彩色多普勒超声检测各组幼鼠血流动力学指标,包括左室射血分数(LVEF)、左心室舒张末内径(LVEDd)、左心室收缩末内径(LVESd)、短轴缩短率(FS)、左室收缩末期容积(ESV)和左室舒张末期容积(EDV),测定各组幼鼠血浆BNP水平。结果:模型对照组和给药组幼鼠体质量均低于空白对照组(P<0.05)。给予对乙酰氨基酚3d后,与模型对照组比较,给药组幼鼠体质量增加(P<0.05)。与模型对照组比较,给药组幼鼠LVEF、FS和EDV升高(P<0.05),而LVEDd、LVESd和ESV降低(P<0.05)。与空白对照组比较,给药组幼鼠LVEF和FS降低(P<0.05),LVEDd、LVESd、EDV和ESV升高,但组间比较差异无统计学意义(P>0.05)。与空白对照组比较,模型对照组幼鼠血浆BNP水平明显升高(P=0.004);与模型对照组比较,给药组幼鼠血浆BNP水平明显降低(P=0.009)。结论:对乙酰氨基酚可通过改善血流动力学指标降低血浆BNP水平,从而对幼鼠左心室功能起保护作用。
Objective:To investigate the effects of acetaminophen on the hemodynamics,left ventricular function and plasma level of brain natriuretic peptide(BNP)in the premature young rats,and to clarify its mechanism in the treatment of patent ductus arteriosus(PDA)in the premature infants.Methods:The pregnant rats were injected intraperitoneally with lipopolysaccharide(LPS)to prepare the premature young rat models.The premature young rats were divided into model control group(n=18)and administration group(n=19);another 10 young rats with normal gestratonal age were selected and used as blank control group.The young rats in blank control group didn't receive any treatment,the young rats in model control group were not given any drug,and the premature young rats in administration group were continunously administrated with acetaminophen for 3 d. Color Doppler ultrasonography was used to detect the hemodynamic parameters of the young rats in various groups,including left ventricular ejection fraction(LVEF),left ventricular end diastolic diameter(LVEDd),left ventricular end systolic diameter(LVESd),fractional shortening(FS),left ventricular end-systolic volume(ESV),and left ventricular end-diastolic volume(EDV).The plasma BNP levels of young rats were detected.Results:The body weights of the young rats in administration group and model control group were lower than that in blank control group(P<0.05).After administration of acetaminophen for 3 d,compared with model control group,the body weight of the young rats in administration group was increased(P<0.05).Compared with model control group,the LVEF,FS and EDV of the young rats in administration group were increased(P<0.05),and the LVEDd,LVESd and ESV of the young rats were decreased(P<0.05).Compared with blank control group,the LVEF and FS of the young rats in administration group were decreased(P<0.05);the LVEDd,LVESd,EDV and ESV of the young rats were increased,but the differences were not statistically significant(P>0.05).Compared with blank control group,the plasma BNP level of the young rats in model control group was significantly increased(P=0.004);compared with model control group,the plasma BNP level of the young rats in administration group was significantly decreased(P=0.009).Conclusion:Acetaminophen can protect the left ventricular function of the young rats by improving the hemodynamic indicators and reducing the plasma BNP level.
Objective:To investigate the effects of acetaminophen on the hemodynamics,left ventricular function and plasma level of brain natriuretic peptide(BNP)in the premature young rats,and to clarify its mechanism in the treatment of patent ductus arteriosus(PDA)in the premature infants.Methods:The pregnant rats were injected intraperitoneally with lipopolysaccharide(LPS)to prepare the premature young rat models.The premature young rats were divided into model control group(n=18)and administration group(n=19);another 10 young rats with normal gestratonal age were selected and used as blank control group.The young rats in blank control group didn't receive any treatment,the young rats in model control group were not given any drug,and the premature young rats in administration group were continunously administrated with acetaminophen for 3 d. Color Doppler ultrasonography was used to detect the hemodynamic parameters of the young rats in various groups,including left ventricular ejection fraction(LVEF),left ventricular end diastolic diameter(LVEDd),left ventricular end systolic diameter(LVESd),fractional shortening(FS),left ventricular end-systolic volume(ESV),and left ventricular end-diastolic volume(EDV).The plasma BNP levels of young rats were detected.Results:The body weights of the young rats in administration group and model control group were lower than that in blank control group(P<0.05).After administration of acetaminophen for 3 d,compared with model control group,the body weight of the young rats in administration group was increased(P<0.05).Compared with model control group,the LVEF,FS and EDV of the young rats in administration group were increased(P<0.05),and the LVEDd,LVESd and ESV of the young rats were decreased(P<0.05).Compared with blank control group,the LVEF and FS of the young rats in administration group were decreased(P<0.05);the LVEDd,LVESd,EDV and ESV of the young rats were increased,but the differences were not statistically significant(P>0.05).Compared with blank control group,the plasma BNP level of the young rats in model control group was significantly increased(P=0.004);compared with model control group,the plasma BNP level of the young rats in administration group was significantly decreased(P=0.009).Conclusion:Acetaminophen can protect the left ventricular function of the young rats by improving the hemodynamic indicators and reducing the plasma BNP level.
引文
[1] Sivanandan S,Agarwal R.Pharmacological closure of patent ductus arteriosus:selecting the agent and route of administration[J].Paediatr Drugs,2016,18(2):123-138.
[2]杨波,王军,高翔羽,等.不同药物治疗早产儿症状动脉导管未闭对前列腺素E2影响的随机对照研究[J].中国新生儿科杂志,2016,31(1):2-8.
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[6]毛璇,李宇宁.对乙酰氨基酚治疗早产儿动脉导管未闭的应用进展[J].临床合理用药,2017,10(7A):180-181.
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[10]蔡淑英,刘振寰,彭桂兰,等.早期运动训练对宫内感染致早产幼鼠运动行为的影响[J].中国儿童保健杂志,2017,25(5):467-469.
[11]舒敏,范娟,谢晓平,等.早产儿动脉导管未闭临床治疗研究的循证医学证据[J].循证医学,2005,23(11):822-824.
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[13]Oncel MY,Yurttutan S,Uras N,et al.An alternative drug(paracetamol)in the management of patent ductus arteriosus in ibuprofen-resistant or contraindicated preterm infants[J].Arch Dis Child Fetal Neonatal Ed,2013,98(1):F94.
[14]Iwanaga Y,Nishi I,Furuichi S,et al.B-type natriuretic peptide strongly reflects diastolic wall stress in patients with chronic heart failure:comparison between systolic and diastolic heart failure[J].J Am Coll Cardiol,2006,47(4):742-748.
[15]胡晓飞,许世佳,孙红,等.三种生物学标志物在心力衰竭患者诊断中的应用[J].中华老年心脑血管病杂志,2018,20(2):161-163.
[16]李金锋,李兰英,王艳丽,等.血浆BNP对评价冠心病心力衰竭治疗疗效的价值[J].中国继续医学教育,2018,10(7):63-65.
[17]Cowie MR, Mendez GF. BNP and congestiveheart failure[J].Prog Cardiovasc Dis,2002,44(4):293-321.
[18]陈默,黄新亮.血浆BNP在心力衰竭者早期诊断及预后预估中的临床意义[J].中国实验诊断学,2018,22(2):221-222.
[19]李正全,田国忠,李梅秀.左室射血分数(LVEF)对大鼠慢性心衰的判定意义[J].黑龙江医药科学,2013,36(3):39-40.
[20]郑淑芳,王燕,张毅,等.轻度心功能不全患者血浆ANP、BNP水平与心脏射血分数的关系[J].山东医药,2010,50(33):45-46.
[21]阚春婷,曹长春.左室射血分数正常、降低的心衰患者血清脑钠肽和甲状腺激素水平对比观察[J].山东医药,2018,58(3):81-82.
[22]单冬凯,杨俊杰,窦冠华,等.冠状动脉CT血管造影获得的无创血流储备分数对心肌缺血的诊断价值[J].解放军医学杂志,2018,43(1):33-37.
[2]杨波,王军,高翔羽,等.不同药物治疗早产儿症状动脉导管未闭对前列腺素E2影响的随机对照研究[J].中国新生儿科杂志,2016,31(1):2-8.
[3]吴东平,朱璐卡.布洛芬与对乙酰氨基酚治疗早产儿症状性动脉导管未闭对患儿血浆和尿前列腺素E2水平的影响[J].实用药物与临床,2017,20(6):657-660.
[4]黄慧洁,尉迟今新,王志杰,等.动脉导管未闭早产儿血NT-proBNP水平变化及其与超声血流动力学指标的相关性[J].山东医药,2017,57(4):80-82.
[5] Hammerman C,Bin-Nun A,Markovitch E,et al.Ductal closure with paracetamol:a surprising new approach to patent ductus arteriosus treatment[J].Pediatrics,2011,128(6):e1618-e1621.
[6]毛璇,李宇宁.对乙酰氨基酚治疗早产儿动脉导管未闭的应用进展[J].临床合理用药,2017,10(7A):180-181.
[7]吴孟娇,万敬员.COX-3:对乙酰氨基酚的作用靶点?[J].生理科学进展,2010,41(1):40-42.
[8] Craham GG,Davies MJ, Day RO,et al. The modern pharmacology of paracetamol:therapeutic actions,mechanism of action,metabolism,toxicity and recent pharmacological findings[J].Inflammopharmacology,2013,21(3):201-232.
[9]李晓捷,高晶,孙忠人.宫内感染致早产鼠脑瘫动物模型制备及其鉴定的实验研究[J].中国康复医学杂志,2004,19(14):885-889.
[10]蔡淑英,刘振寰,彭桂兰,等.早期运动训练对宫内感染致早产幼鼠运动行为的影响[J].中国儿童保健杂志,2017,25(5):467-469.
[11]舒敏,范娟,谢晓平,等.早产儿动脉导管未闭临床治疗研究的循证医学证据[J].循证医学,2005,23(11):822-824.
[12]Anderson BJ.Paracetamol(Acetaminophen):mechanisms of action[J].Paediatr Anaesth,2008,18(10):915-921.
[13]Oncel MY,Yurttutan S,Uras N,et al.An alternative drug(paracetamol)in the management of patent ductus arteriosus in ibuprofen-resistant or contraindicated preterm infants[J].Arch Dis Child Fetal Neonatal Ed,2013,98(1):F94.
[14]Iwanaga Y,Nishi I,Furuichi S,et al.B-type natriuretic peptide strongly reflects diastolic wall stress in patients with chronic heart failure:comparison between systolic and diastolic heart failure[J].J Am Coll Cardiol,2006,47(4):742-748.
[15]胡晓飞,许世佳,孙红,等.三种生物学标志物在心力衰竭患者诊断中的应用[J].中华老年心脑血管病杂志,2018,20(2):161-163.
[16]李金锋,李兰英,王艳丽,等.血浆BNP对评价冠心病心力衰竭治疗疗效的价值[J].中国继续医学教育,2018,10(7):63-65.
[17]Cowie MR, Mendez GF. BNP and congestiveheart failure[J].Prog Cardiovasc Dis,2002,44(4):293-321.
[18]陈默,黄新亮.血浆BNP在心力衰竭者早期诊断及预后预估中的临床意义[J].中国实验诊断学,2018,22(2):221-222.
[19]李正全,田国忠,李梅秀.左室射血分数(LVEF)对大鼠慢性心衰的判定意义[J].黑龙江医药科学,2013,36(3):39-40.
[20]郑淑芳,王燕,张毅,等.轻度心功能不全患者血浆ANP、BNP水平与心脏射血分数的关系[J].山东医药,2010,50(33):45-46.
[21]阚春婷,曹长春.左室射血分数正常、降低的心衰患者血清脑钠肽和甲状腺激素水平对比观察[J].山东医药,2018,58(3):81-82.
[22]单冬凯,杨俊杰,窦冠华,等.冠状动脉CT血管造影获得的无创血流储备分数对心肌缺血的诊断价值[J].解放军医学杂志,2018,43(1):33-37.