IGF, CNRS, INSERM, Univ Montpellier, Montpellier, France.
Laboratory of Excellence Ion Channel Science and Therapeutics, Valbonne, France.
Sci Rep. 2017 Oct 31;7(1):14701. doi: 10.1038/s41598-017-14822-x.
MLC901, a traditional Chinese medicine containing a cocktail of active molecules, both reduces cerebral infarction and improves recovery in patients with ischemic stroke. The aim of this study was to evaluate the acute and long-term benefits of MLC901 in ischemic and reperfused mouse hearts. Ex vivo, under physiological conditions, MLC901 did not show any modification in heart rate and contraction amplitude. However, upon an ischemic insult, MLC901 administration during reperfusion, improved coronary flow in perfused hearts. In vivo, MLC901 (4 µg/kg) intravenous injection 5 minutes before reperfusion provided a decrease in both infarct size (49.8%) and apoptosis (49.9%) after 1 hour of reperfusion. Akt and ERK1/2 survival pathways were significantly activated in the myocardium of those mice. In the 4-month clinical follow-up upon an additional continuous per os administration, MLC901 treatment decreased cardiac injury as revealed by a 45%-decrease in cTnI plasmatic concentrations and an improved cardiac performance assessed by echocardiography. A histological analysis revealed a 64%-decreased residual scar fibrosis and a 44%-increased vascular density in the infarct region. This paper demonstrates that MLC901 treatment was able to provide acute and long-term cardioprotective effects in a murine model of myocardial ischemia-reperfusion injury in vivo.
MLC901 是一种中药，含有多种活性分子，既能减少脑梗死，又能改善缺血性中风患者的恢复。本研究旨在评估 MLC901 对缺血再灌注小鼠心脏的急性和长期益处。在体外用生理条件下，MLC901 对心率和收缩幅度没有任何改变。然而，在缺血性损伤后，再灌注时给予 MLC901 治疗可改善灌流心脏的冠状动脉流量。在体内，再灌注前 5 分钟静脉注射 MLC901（4μg/kg）可减少再灌注 1 小时后的梗死面积（49.8%）和细胞凋亡（49.9%）。Akt 和 ERK1/2 存活途径在这些小鼠的心肌中显著激活。在随后的 4 个月临床随访中，连续口服给予 MLC901 治疗可降低 cTnI 血浆浓度，改善心脏功能，通过超声心动图评估。组织学分析显示，梗死区域的残余瘢痕纤维化减少了 64%，血管密度增加了 44%。本研究表明，MLC901 治疗能够为体内缺血再灌注损伤的小鼠模型提供急性和长期的心脏保护作用。
