二氟甲基鸟氨酸对异丙肾上腺素诱导的大鼠心肌肥厚的影响
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摘要
目的研究二氟甲基鸟氨酸(DFMO)对异丙肾上腺素诱导的大鼠心肌肥厚的影响。方法按照体重将大鼠随机分为3组:对照组、模型组和实验组,每组15只。实验组给予2%二氟甲基鸟氨酸,对照组与模型组皮下注射0. 9%Na Cl,均4周。以异丙肾上腺素5 mg·kg~(-1)连续皮下注射1周复制心肌肥大模型。计算心脏指数;用Msaaon染色评价纤维化程度;以实时荧光定量PCR测定心房钠尿肽(ANP)、鸟氨酸脱羧酶(ODC)和精脒/精胺乙酰转移酶(SSAT)mRNA水平。结果对照组、模型组、实验组的心脏指数(mg·g~(-1))分别为3. 49±0. 21,3. 76±0. 32和3. 55±0. 27;这3组的间质纤维化率分别为(6±2)%,(24±5)%和(14±2)%;这3组的ANP mRNA表达水平分别为0. 60±0. 08,1. 20±0. 44和0. 65±0. 13;这3组的ODC mRNA表达水平分别为0. 95±0. 19,1. 67±0. 21和1. 17±0. 09;这3组的SSAT mRNA表达水平分别为0. 95±0. 28,1. 57±0. 18和1. 85±0. 17。上述指标,模型组与对照组比较,差异均有统计学意义(均P <0. 05);实验组与模型组比较,差异均有统计学意义(均P <0. 05)。结论 DFMO对大鼠心肌肥厚有保护作用,其机制与降低多胺合成代谢和增强分解代谢有关。
Objective To investigate the effect of α-difluoromethylornithine( DFMO) on cardiac hypertrophy induced by isoproterenol( ISO)in rats. Methods Wistar rats were randomly divided into 3 groups: control group,model group,and experimental group,15 rats in each group.The rats in experimental group were treated with 2% DFMO water for 4 weeks; the rats in control and model groups were treated with 0. 9%NaCl,once a day for 4 weeks. Model rats was established by subcutaneously ISO 5 mg·kg~(-1)·d~(-1),once daily for 1 week. The heart index was calculated. The interstitial fibrosis was evaluated by cardiac index and Masson staining. The mRNA expression of the atrial natriuretic peptide( ANP),ornithine decarboxylase( ODC),spermidine/spermine N1-acetyltransferase( SSAT) were determined by realtime polymerase chain reaction. Results The heart index( mg·g~(-1)) in control group,model group and experimental group were respectively 3. 49 ± 0. 21,3. 76 ± 0. 32,3. 55 ± 0. 27; the ratio of collagen fibers in the 3 groups were respectively( 6 ± 2) %,( 24 ± 5) %,( 14 ± 2) %; the ANP mRNAin the 3 groups were respectively 0. 60 ± 0. 08,1. 20 ± 0. 44,0. 65 ± 0. 13; the ODC mRNA in the 3 groups were respectively 0. 95 ± 0. 19,1. 67 ± 0. 21,1. 17 ± 0. 09; the SSAT mRNA in the 3 groups were respectively 0. 95 ± 0. 28,1. 57 ± 0. 18,1. 85 ± 0. 17. The difference of above factors between the model group and the control group was statistically significant( all P < 0. 05). The difference of above factors between the experimental group and the model group was statistically significant( all P < 0. 05). Conclusion DFMO had a protective effect on myocardial hypertrophy,and its mechanism was related to the reduction of anabolism and the enhancement of catabolism of polyamine.
Objective To investigate the effect of α-difluoromethylornithine( DFMO) on cardiac hypertrophy induced by isoproterenol( ISO)in rats. Methods Wistar rats were randomly divided into 3 groups: control group,model group,and experimental group,15 rats in each group.The rats in experimental group were treated with 2% DFMO water for 4 weeks; the rats in control and model groups were treated with 0. 9%NaCl,once a day for 4 weeks. Model rats was established by subcutaneously ISO 5 mg·kg~(-1)·d~(-1),once daily for 1 week. The heart index was calculated. The interstitial fibrosis was evaluated by cardiac index and Masson staining. The mRNA expression of the atrial natriuretic peptide( ANP),ornithine decarboxylase( ODC),spermidine/spermine N1-acetyltransferase( SSAT) were determined by realtime polymerase chain reaction. Results The heart index( mg·g~(-1)) in control group,model group and experimental group were respectively 3. 49 ± 0. 21,3. 76 ± 0. 32,3. 55 ± 0. 27; the ratio of collagen fibers in the 3 groups were respectively( 6 ± 2) %,( 24 ± 5) %,( 14 ± 2) %; the ANP mRNAin the 3 groups were respectively 0. 60 ± 0. 08,1. 20 ± 0. 44,0. 65 ± 0. 13; the ODC mRNA in the 3 groups were respectively 0. 95 ± 0. 19,1. 67 ± 0. 21,1. 17 ± 0. 09; the SSAT mRNA in the 3 groups were respectively 0. 95 ± 0. 28,1. 57 ± 0. 18,1. 85 ± 0. 17. The difference of above factors between the model group and the control group was statistically significant( all P < 0. 05). The difference of above factors between the experimental group and the model group was statistically significant( all P < 0. 05). Conclusion DFMO had a protective effect on myocardial hypertrophy,and its mechanism was related to the reduction of anabolism and the enhancement of catabolism of polyamine.
引文
[1]魏世杰,周家伟,甘梦月,等.苦参碱对心脏肥厚大鼠的心功能和左室重塑的改善作用[J].中国临床药理学杂志,2017,33(4):338-342.
[2]林岩,肖薇,李波,等.二氟甲基鸟氨酸对异丙肾上腺素诱导的心肌细胞肥大与凋亡的影响[J].中国药理学通报,2015,31(5):668-672.
[3]LIU L,WANG C,LIN Y.Suppression of calcium-sensing receptor ameliorates cardiac hypertrophy through inhibition of autophagy[J].Mol Med Reports,2016,14(1):111-120.
[4]LIN Y,WANG L N,XI Y H,et al.L-Arginine inhibits isoproterenol-induced cardiac hypertrophy through nitric oxide and polyamine pathways[J].Basic Clin Pharmacol Toxicol,2008,103(2):124-130.
[5]姚秀云,杨育红,宋莹,等.左卡尼汀对异丙肾上腺素诱导大鼠心肌肥厚的保护作用及机制研究[J].中国药理学通报,2012,28(4):540-544.
[6]LIN Y,ZHU J B,ZHANG X J,et al.Inhibition of cardiomyocytes hypertrophy by resveratrol is associated with amelioration of endoplasmic reticulum stress[J].Cell Physiol Biochem,2016,39:(2)780-789.
[7]高慧,李澜,倪晶宇,等.β-肾上腺素能受体在心血管系统中作用的研究进展[J].中国临床药理学杂志,2016,32(20):1918-1924.
[8]史婷婷,白建平,梁月琴,等.芹菜素对大鼠缺血/再灌注心肌细胞凋亡及相关蛋白Bcl-2、Bax、Caspase-3表达的影响[J].中国药理学通报,2011,27(5):666-671.
[9]TIPNIS U R,HE G Y,LI S,et al.Attenuation of isoproterenol-mediated myocardial injury in rat by an inhibitor of polyamine synthesis[J].Cardiovas Pathol,2000,9(5):273-280.
[10]TANTINI B,FIUMANA E,CETRULLO S,Involvement of polyamines in apoptosis of cardiac myoblasts in a model of simulated ischemia[J].J Mol Cell Cardiol,2006,40(6):775-782.
[2]林岩,肖薇,李波,等.二氟甲基鸟氨酸对异丙肾上腺素诱导的心肌细胞肥大与凋亡的影响[J].中国药理学通报,2015,31(5):668-672.
[3]LIU L,WANG C,LIN Y.Suppression of calcium-sensing receptor ameliorates cardiac hypertrophy through inhibition of autophagy[J].Mol Med Reports,2016,14(1):111-120.
[4]LIN Y,WANG L N,XI Y H,et al.L-Arginine inhibits isoproterenol-induced cardiac hypertrophy through nitric oxide and polyamine pathways[J].Basic Clin Pharmacol Toxicol,2008,103(2):124-130.
[5]姚秀云,杨育红,宋莹,等.左卡尼汀对异丙肾上腺素诱导大鼠心肌肥厚的保护作用及机制研究[J].中国药理学通报,2012,28(4):540-544.
[6]LIN Y,ZHU J B,ZHANG X J,et al.Inhibition of cardiomyocytes hypertrophy by resveratrol is associated with amelioration of endoplasmic reticulum stress[J].Cell Physiol Biochem,2016,39:(2)780-789.
[7]高慧,李澜,倪晶宇,等.β-肾上腺素能受体在心血管系统中作用的研究进展[J].中国临床药理学杂志,2016,32(20):1918-1924.
[8]史婷婷,白建平,梁月琴,等.芹菜素对大鼠缺血/再灌注心肌细胞凋亡及相关蛋白Bcl-2、Bax、Caspase-3表达的影响[J].中国药理学通报,2011,27(5):666-671.
[9]TIPNIS U R,HE G Y,LI S,et al.Attenuation of isoproterenol-mediated myocardial injury in rat by an inhibitor of polyamine synthesis[J].Cardiovas Pathol,2000,9(5):273-280.
[10]TANTINI B,FIUMANA E,CETRULLO S,Involvement of polyamines in apoptosis of cardiac myoblasts in a model of simulated ischemia[J].J Mol Cell Cardiol,2006,40(6):775-782.
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