Liu Meiyan, Wei Wanlin, Stone Christopher R, Zhang Lijun, Tian Guoxiang, Ding Jessie N
Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, People's Republic of China.
Department of Cardiology, PLA Army General Hospital, Beijing, People's Republic of China.
Neuropsychiatr Dis Treat. 2018 Mar 16;14:787-797. doi: 10.2147/NDT.S157441. eCollection 2018.
Trimetazidine is an anti-ischemic drug that can inhibit platelet aggregation and regulate serotonin (5-hydroxytryptamine [5-HT]) release. The purpose of this study was to investigate the therapeutic effects of trimetazidine on 5-HT and serotonin transporter (SERT) expression in experimentally induced myocardial infarction (MI), depression, and MI + depression.
Eighty Sprague Dawley (SD) rats were randomly divided into a trimetazidine group and a saline group of 40 rats each. The trimetazidine group was given trimetazidine pretreatment for 4 weeks, while the saline group received saline for 4 weeks. Both groups were then subdivided into four subgroups (n=10), which were each subjected to a unique disease condition: sham surgery, MI, depression, or MI + depression. All rats were sacrificed 3 days thereafter, and serum and platelet levels of 5-HT and SERT were assessed. In addition, we experimented with trimetazidine posttreatment. Twenty SD rats underwent MI surgery, and were then randomly divided into a treatment and a saline group (n=10 each). For 4 weeks post-surgery, the trimetazidine group was given trimetazidine, while the saline group received saline. Serum and platelet levels of 5-HT and SERT were assessed.
Pretreatment with trimetazidine: in the nontreatment saline group, MI, depression, and MI + depression showed significant declines (<0.05) in both serum and platelet 5-HT levels compared to sham. Trimetazidine treatment significantly increased serum and platelet 5-HT levels in the MI, depression, and MI + depression (<0.05) subgroups compared to their counterparts in the saline group. Results for SERT were heterogeneous between serum and platelets. Trimetazidine treatment significantly decreased serum levels of SERT in the sham surgery subgroup (<0.05), while significantly increasing levels in depression rats, compared to control (<0.05). In platelets, trimetazidine significantly decreased SERT in sham surgery, MI, depression, and MI + depression rats, compared to control (<0.05). This contrast suggests that trimetazidine has opposite effects in serum and platelet SERT levels for the three disease models. Post-surgery trimetazidine: increased serum 5-HT (<0.05) and serum SERT (<0.05) were observed, compared to control. In platelets, trimetazidine decreased both 5-HT and SERT compared to control, significantly (<0.05) for 5-HT, but not significantly for SERT (>0.05).
Trimetazidine has a regulatory effect on 5-HT and SERT in the serum and platelets. Because of the downstream effects of this regulation on blood vessel function and myocardial protection, trimetazidine may be a therapeutic or preventive agent in several disease processes, including MI, depression, and the comorbidity between these two diseases. Further investigation, aimed at exploring the clinical potential of trimetazidine, is therefore warranted.
曲美他嗪是一种抗缺血药物，可抑制血小板聚集并调节血清素（5-羟色胺[5-HT]）释放。本研究的目的是探讨曲美他嗪对实验性诱导的心肌梗死（MI）、抑郁症以及MI+抑郁症中5-HT和血清素转运体（SERT）表达的治疗作用。
80只Sprague Dawley（SD）大鼠随机分为曲美他嗪组和生理盐水组，每组40只。曲美他嗪组给予曲美他嗪预处理4周，而生理盐水组给予生理盐水4周。然后将两组再细分为四个亚组（n=10），每个亚组接受一种独特的疾病状态：假手术、MI、抑郁症或MI+抑郁症。此后3天处死所有大鼠，评估血清和血小板中5-HT和SERT的水平。此外，我们进行了曲美他嗪的术后治疗实验。20只SD大鼠接受MI手术，然后随机分为治疗组和生理盐水组（每组n=10）。术后4周，曲美他嗪组给予曲美他嗪，而生理盐水组给予生理盐水。评估血清和血小板中5-HT和SERT的水平。
曲美他嗪预处理：在未治疗的生理盐水组中，与假手术相比，MI、抑郁症和MI+抑郁症组的血清和血小板5-HT水平均显著下降（<0.05）。与生理盐水组的对应亚组相比，曲美他嗪治疗显著提高了MI、抑郁症和MI+抑郁症亚组的血清和血小板5-HT水平（<0.05）。血清和血小板中SERT的结果存在异质性。与对照组相比，曲美他嗪治疗显著降低了假手术亚组的血清SERT水平（<0.05），而显著提高了抑郁症大鼠的SERT水平（<0.05）。在血小板中，与对照组相比，曲美他嗪显著降低了假手术、MI、抑郁症和MI+抑郁症大鼠的SERT水平（<0.05）。这种差异表明，曲美他嗪在三种疾病模型的血清和血小板SERT水平上具有相反的作用。术后曲美他嗪治疗：与对照组相比，观察到血清5-HT升高（<,0.05）和血清SERT升高（<0.05）。在血小板中，与对照组相比，曲美他嗪降低了5-HT和SERT，5-HT显著降低（<0.05），但SERT未显著降低（>0.05）。
曲美他嗪对血清和血小板中的5-HT和SERT具有调节作用。由于这种调节对血管功能和心肌保护的下游影响，曲美他嗪可能是包括MI、抑郁症以及这两种疾病合并症在内的多种疾病过程中的治疗或预防药物。因此，有必要进一步研究以探索曲美他嗪的临床潜力。
