Huuskonen Christa, Hämäläinen Mari, Paavonen Timo, Moilanen Eeva, Mennander Ari
Tampere University Heart Hospital, Cardiac Research and Tampere University; Tampere-Finland.
Anatol J Cardiol. 2019 Jan;21(1):39-45. doi: 10.14744/AnatolJCardiol.2018.37336.
The molecular pathway leading to myocardial cellular destruction after acute volume overload (AVO) may include monoamine oxidases. The aim of the present study was to investigate whether moclobemide (Mo), a monoamine oxidase inhibitor, protects the myocardium after AVO.
Sixty syngeneic Fischer rats underwent surgical abdominal aortocaval fistula to induce AVO. Eighteen rats were treated with Mo 10 mg/kg/day and were compared with 42 untreated rats with AVO without treatment. Myocardial recovery was analyzed using quantitative reverse transcription polymerase chain reaction for hypoxia-inducible factor 1-alpha, inducible nitric oxide synthase, interleukin 6, E-selectin, atrial natriuretic peptide (ANP), brain natriuretic peptide, vascular endothelial growth factor-alpha, matrix metalloproteinase 9, chitinase 3-like protein (YKL-40), and transforming growth factor-beta.
After 3 days, the relative number of ischemic intramyocardial arteries in the left ventricle was lower in AVO treated with Mo than in without [0.04 (0.02-0.07) vs. 0.09 (0.07-0.14), point score unit]. After 1 day, ANP was lower in AVO treated with Mo than in without [0.95 (0.37-1.84) vs. 2.40 (1.33-3.09), fold changes from the baseline (FC), p=0.044], whereas after 1 and 3 days, YKL-40 was higher in AVO treated with Mo than in without [22.66 (14.05-28.83) vs. 10.06 (6.23-15.02), FC, p=0.006 and 6.03 (4.72-7.18) vs. 3.70 (2.62-5.35), FC, p=0.025].
Mo decreases intramyocardial arterial ischemia of the left ventricle after AVO while increases YKL-40, reflecting cellular protection during early cardiac remodeling. In the future, adding Mo may be a simple means for myocardial protection after AVO.
急性容量超负荷（AVO）后导致心肌细胞破坏的分子途径可能包括单胺氧化酶。本研究的目的是调查单胺氧化酶抑制剂吗氯贝胺（Mo）是否能在AVO后保护心肌。
60只同基因的Fischer大鼠接受腹部主动脉腔静脉瘘手术以诱导AVO。18只大鼠接受10mg/kg/天的Mo治疗，并与42只未治疗的AVO大鼠进行比较。使用定量逆转录聚合酶链反应分析心肌恢复情况，检测缺氧诱导因子1-α、诱导型一氧化氮合酶、白细胞介素6、E-选择素、心房利钠肽（ANP）、脑利钠肽、血管内皮生长因子-α、基质金属蛋白酶9、几丁质酶3样蛋白（YKL-40）和转化生长因子-β。
3天后，接受Mo治疗的AVO大鼠左心室内缺血性心肌内动脉的相对数量低于未治疗的大鼠[0.04（0.02 - 0.07）对0.09（0.07 - 0.14），评分单位]。1天后，接受Mo治疗的AVO大鼠的ANP低于未治疗的大鼠[0.95（0.37 - 1.84）对2.40（1.33 - 3.09），相对于基线的变化倍数（FC），p = 0.044]，而在1天和3天后，接受Mo治疗的AVO大鼠的YKL-40高于未治疗的大鼠[22.66（14.05 - 28.83）对10.06（6.23 - 15.02），FC，p = 0.006；6.03（4.72 - 7.18）对3.70（2.62 - 5.35），FC，p = 0.025]。
Mo可减少AVO后左心室心肌内动脉缺血，同时增加YKL-40，反映了早期心脏重塑过程中的细胞保护作用。未来，添加Mo可能是AVO后心肌保护的一种简单方法。
