Biomedical Engineering Research Center, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming, 650500, Yunnan, China.
Department of Nuclear Medicine, Third People's Hospital of Honghe State, Honghe, 661000, China.
J Physiol Biochem. 2019 Nov;75(4):531-547. doi: 10.1007/s13105-019-00702-7. Epub 2019 Aug 22.
Inflammation is a pivotal feature of myocardial reperfusion-induced microvascular injury and dysfunction. However, the molecular mechanisms by which myocardial reperfusion triggered inflammation remain incurable. The NLRP3 inflammasome is a key intracellular sensor that detection of cellular stress to activation of caspase-1, and consequent IL-1β maturation and pyroptotic cell death. Here, we showed that NLRP3 inflammasome played a key role in myocardial reperfusion-induced microvascular injury. We observed NLRP3 inflammasome activation and pyroptosis in both cardiac microvascular endothelial cells and myocardial I/R animal model. Gastrodin, an effective monomeric component extracted from the herb Gastrodia elata BIume, blocked cardiac microvascular endothelial cell pyroptosis via inhibiting NLRP3/caspase-1 pathway. Gastrodin also reduced interleukin-1β (IL-1β) production in vivo and in vitro. Furthermore, gastrodin treatment attenuated infarct size and inflammatory cells infiltration and increased capillary formation. Gastrodin is thus a potential therapeutic for NLRP3-associated inflammatory disease.
炎症是心肌再灌注诱导的微血管损伤和功能障碍的关键特征。然而，心肌再灌注触发炎症的分子机制仍无法治愈。NLRP3 炎性体是一种关键的细胞内传感器，可检测细胞应激以激活 caspase-1，进而导致 IL-1β 成熟和细胞焦亡。在这里，我们表明 NLRP3 炎性体在心肌再灌注诱导的微血管损伤中起关键作用。我们观察到 NLRP3 炎性体激活和细胞焦亡在心脏微血管内皮细胞和心肌 I/R 动物模型中均存在。天麻素是从天麻中提取的一种有效的单体成分，通过抑制 NLRP3/caspase-1 途径阻断心脏微血管内皮细胞的细胞焦亡。天麻素还减少了体内和体外白细胞介素-1β (IL-1β) 的产生。此外，天麻素治疗可减轻梗死面积和炎症细胞浸润，增加毛细血管形成。因此，天麻素是一种治疗 NLRP3 相关炎症性疾病的潜在药物。
