[Impact of trimetazidine pre-treatment on 5-hydroxytryptamine and serotonin transporter in rats with experimental myocardial infarction and depression]

Zhonghua Xin Xue Guan Bing Za Zhi. 2017 Feb 24;45(2):137-141. doi: 10.3760/cma.j.issn.0253-3758.2017.02.013.
[Article in Chinese]

Abstract

Objective: To explore the effect of trimetazidine pre-treatments on serum 5-hydroxytryptamine (5-HT) and serotonin transporter (SERT), platelet 5-HT and SERT in the Sprague Dawley rats with myocardial infarction(MI), depression, and myocardial infarction co-exist with depression (MI+ depression) and in sham operated rats. Methods: Eighty rats were divided into treatment group and placebo (saline) group by the random number table method (n=40 each group). After 4 weeks' treatment with trimetazidine, or saline, these rats were assigned to respective sham subgroup, depression subgroup, MI subgroup, MI + depression subgroup (n=10 each subgroup). All rats were sacrificed 3 days later. 5-HT in serum and platelet, and SERT in serum and platelet of the rats were tested by enzyme linked immunosorbent assay (ELISA). Data were analyzed by SPSS 17.0. Results: In saline group, serum and platelet 5-HT levels were significantly lower in MI, depression and MI+ depression subgroup compared to sham subgroup (all P<0.01). In trimetazidine pre-treatment group, serum and platelet 5-HT levels were significantly higher in the depression subgroup, MI subgroup, MI + depression subgroup than respective subgroups of saline pretreated rats (all P<0.01). In saline group, SERT in serum and platelet were higher in MI, depression, MI+ depression subgroup than the sham subgroup and statistical significance was found between MI+ depression subgroup and sham subgroups. Serum SERT level was significantly lower in the treatment group compared to saline group for sham rats (P<0.01). In treatment group, serum SERT level was higher in MI, depression and MI+ depression subgroups compared to respective subgroup treated with saline while the statistical significance was found in depression subgroup between trimetazidine pre-treatment and saline control groups. Platelet SERT was higher in MI, depression and MI+ depression subgroups compared to sham subgroup post saline treatment. Platelet SERT was significantly lower in MI, depression and MI+ depression subgroups post trimetazidine pre-treatment than in respective subgroups post saline treatment (all P<0.01). Conclusions: Our study results indicate that trimetazidine pretreatment could increase the levels of 5-HT and SERT in serum and 5-HT in platelet, and decrease the level of SERT in platelet in the rat MI and depression model.

目的:探讨药物前期干预对假手术、心肌梗死(心梗)、抑郁、心梗合并抑郁4种大鼠模型血清和血小板5-羟色胺(5-HT)、5-羟色胺转运体(SERT)的影响。 方法:将80只Sprague Dawley(SD)大鼠按随机数字表法分为治疗组和对照组,每组40只,分别予曲美他嗪和生理盐水前期干预4周。随后再将两组各分为4个亚组,即假手术、心梗、抑郁、心梗合并抑郁亚组,每组各10只大鼠。各组模型建立成功3 d后处死动物,采用酶联免疫吸附实验检测各组大鼠血清和血小板5-HT、SERT浓度。 结果: (1)各组大鼠血清5-HT浓度:对照组中,心梗、抑郁、心梗合并抑郁亚组大鼠血清5-HT浓度均明显低于假手术亚组(P均<0.01)。治疗组中,心梗、抑郁、心梗合并抑郁亚组大鼠血清5-HT浓度均明显高于对照组中的相应亚组(P均<0.01)。(2)各组大鼠血小板5-HT浓度:对照组中,心梗、抑郁、心梗合并抑郁亚组大鼠血小板5-HT浓度均明显低于假手术亚组(P均<0.01)。治疗组中,假手术、心梗、抑郁、心梗合并抑郁亚组大鼠血小板5-HT浓度均明显高于对照组中的相应亚组(P均<0.01)。(3)各组大鼠血清SERT浓度:对照组中,心梗、抑郁、心梗合并抑郁亚组大鼠血清SERT浓度均高于假手术亚组,但只有心梗合并抑郁亚组差异有统计学意义(P<0.01)。治疗组中,假手术亚组大鼠血清SERT浓度明显低于对照组中的假手术亚组(P<0.01),心梗、抑郁、心梗合并抑郁亚组大鼠血清SERT浓度均高于对照组中的相应亚组,但只有抑郁亚组差异有统计学意义(P<0.01)。(4)各组大鼠血小板SERT浓度:对照组中,心梗、抑郁、心梗合并抑郁亚组大鼠血小板SERT浓度均高于假手术亚组,但差异均无统计学意义。治疗组中,假手术、心梗、抑郁、心梗合并抑郁亚组大鼠血小板SERT浓度均明显低于对照组中的相应亚组(P均<0.01)。 结论:曲美他嗪可以升高心肌梗死合并抑郁大鼠血清5-HT、SERT及血小板5-HT水平,降低血小板SERT水平。.

Keywords: Depression; Myocardial infarction; Serotonin; Trimetazidine.

MeSH terms

  • Animals
  • Depression*
  • Enzyme-Linked Immunosorbent Assay
  • Myocardial Infarction*
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin
  • Serotonin Plasma Membrane Transport Proteins
  • Trimetazidine / pharmacology*
  • Vasodilator Agents / pharmacology*

Substances

  • Serotonin Plasma Membrane Transport Proteins
  • Vasodilator Agents
  • Serotonin
  • Trimetazidine