Yu Ping, Li Yuangeng, Fu Wenwen, Li Xin, Liu Yanzhe, Wang Yaozhen, Yu Xiaofeng, Xu Huali, Sui Dayun
Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, Changchun, China.
Front Pharmacol. 2021 Jan 15;11:607813. doi: 10.3389/fphar.2020.607813. eCollection 2020.
At present, many patients who undergo reperfusion immediately after percutaneous coronary intervention will undergo microvascular obstruction and reduction in myocardial blood flow. This phenomenon is called "no-reflow (NR)," and there is still no effective therapy for NR. Studies showed saponins (PQS) have effect on MI/R injury, while the effect and mechanism of PQS on MI/R induced NR are not clear. In this study, we established a MI/R model to investigate whether PQS decrease NR phenomenon suppression of inflammation. We found that PQS significantly alleviated the symptoms of NR by reducing ischemia, infarction, and NR area; improving cardiac function; preventing pathological morphology changes of myocardium; depressing leukocytes' aggregation and adhesion; and suppressing the excessive inflammation. Further study demonstrated that PQS remarkably inhibited TLR4, MyD88, p-NF-κB, and NLRP3 inflammasome-associated protein, and these effects could be reversed by LPS. These results indicated that PQS may protect NR by inhibiting the activation of NLRP3 inflammasome TLR4/MyD88/NF-κB signaling pathway in part, suggesting that PQS exist potential in preventing NR induced by MI/R.
目前，许多在经皮冠状动脉介入治疗后立即进行再灌注的患者会出现微血管阻塞和心肌血流减少的情况。这种现象被称为“无复流（NR）”，且目前仍没有针对NR的有效治疗方法。研究表明，人参皂苷（PQS）对心肌缺血/再灌注损伤有作用，而PQS对心肌缺血/再灌注诱导的NR的作用及机制尚不清楚。在本研究中，我们建立了心肌缺血/再灌注模型，以研究PQS是否通过抑制炎症来减轻NR现象。我们发现，PQS通过减少缺血、梗死和NR面积；改善心脏功能；防止心肌病理形态学改变；抑制白细胞聚集和黏附；以及抑制过度炎症反应，显著减轻了NR症状。进一步研究表明，PQS显著抑制了TLR4、MyD88、p-NF-κB和NLRP3炎性小体相关蛋白，且这些作用可被脂多糖逆转。这些结果表明，PQS可能部分通过抑制NLRP3炎性小体的激活及TLR4/MyD88/NF-κB信号通路来保护NR，提示PQS在预防心肌缺血/再灌注诱导的NR方面具有潜在价值。
