Donepezil, anti-Alzheimer's disease drug, prevents cardiac rupture during acute phase of myocardial infarction in mice.
Donepezil, anti-Alzheimer's disease drug, prevents cardiac rupture during acute phase of myocardial infarction in mice.
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DOI：
10.1371/journal.pone.0020629
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Sato T
中科院分区：
文献类型：
--
作者：
Arikawa M;Kakinuma Y;Handa T;Yamasaki F;Sato T
我们之前已经证明，多奈哌齐（一种乙酰胆碱酯酶抑制剂）对胆碱能系统的慢性干预在抑制心肌梗死（MI）后的长期心脏重构中起有益作用。然而，与这种慢性效应相比，多奈哌齐在心肌梗死急性期的急性效应尚不清楚。注意到最近发现的抗炎作用的胆碱能机制，我们验证了多奈哌齐减轻心肌梗死后急性炎症组织损伤的假设。在分离和活化的巨噬细胞中，多奈哌齐显著降低细胞内和细胞外基质金属蛋白酶-9 （MMP-9）。在心肌梗死小鼠中，尽管心率和血压值相当，但在心肌梗死急性期，多奈哌齐治疗组的心脏破裂发生率明显低于未治疗组。免疫组化显示，MMP-9定位于包括巨噬细胞在内的大量炎症细胞浸润的梗死区，多奈哌齐组大鼠左室梗死区MMP-9表达及酶活性明显降低。本研究提示，多奈哌齐可抑制梗死心肌中mmp -9相关的急性炎性组织损伤，从而降低心肌梗死急性期左心室游离壁破裂的风险。
We have previously demonstrated that the chronic intervention in the cholinergic system by donepezil, an acetylcholinesterase inhibitor, plays a beneficial role in suppressing long-term cardiac remodeling after myocardial infarction (MI). In comparison with such a chronic effect, however, the acute effect of donepezil during an acute phase of MI remains unclear. Noticing recent findings of a cholinergic mechanism for anti-inflammatory actions, we tested the hypothesis that donepezil attenuates an acute inflammatory tissue injury following MI. In isolated and activated macrophages, donepezil significantly reduced intra- and extracellular matrix metalloproteinase-9 (MMP-9). In mice with MI, despite the comparable values of heart rate and blood pressure, the donepezil-treated group showed a significantly lower incidence of cardiac rupture than the untreated group during the acute phase of MI. Immunohistochemistry revealed that MMP-9 was localized at the infarct area where a large number of inflammatory cells including macrophages infiltrated, and the expression and the enzymatic activity of MMP-9 at the left ventricular infarct area was significantly reduced in the donepezil-treated group. The present study suggests that donepezil inhibits the MMP-9-related acute inflammatory tissue injury in the infarcted myocardium, thereby reduces the risk of left ventricular free wall rupture during the acute phase of MI.
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影响因子：
3.1
作者：
Akaike, Akinori;Takada-Takatori, Yuki;Izumi, Yasuhiko
通讯作者：
Izumi, Yasuhiko
DOI：
10.1152/ajpheart.00207.2003
发表时间：
2003-09-01
影响因子：
4.8
作者：
Hayashidani, S;Tsutsui, H;Takeshita, A
通讯作者：
Takeshita, A
影响因子：
37.8
作者：
Ando, M;Katare, RG;Sato, T
通讯作者：
Sato, T
影响因子：
2.9
作者：
DonnellyRoberts, DL;Xue, IC;Sullivan, JP
通讯作者：
Sullivan, JP
影响因子：
6
作者：
Fang, Lu;Gao, Xiao-Ming;Du, Xiao-Jun
通讯作者：
Du, Xiao-Jun