Wang Yaqiong, Yan Xiaoxiang, Mi Shouling, Li Zhang, Wang Yuexiang, Zhu Hong, Sun Xiaolei, Zhao Buchang, Zhao Chao, Zou Yunzeng, Hu Kai, Ding Xiaoqiang, Sun Aijun, Ge Junbo
Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.
J Cell Mol Med. 2017 Jan;21(1):4-12. doi: 10.1111/jcmm.12915. Epub 2016 Oct 26.
Naoxintong (NXT) is a Chinese Materia Medica standardized product extracted from 16 various kinds of Chinese traditional herbal medicines including Salvia miltiorrhiza, Angelica sinensis, Astragali Radix. Naoxintong is clinically effective in treating ischaemia heart disease. Nucleotide-binding oligomerization domain-Like Receptor with a Pyrin domain 3 (NLRP3) inflammasome has been critically involved in myocardial ischaemia/reperfusion (I/R) injury. Here, we have been suggested that NXT might attenuate myocardial I/R injury via suppression of NLRP3 inflammasome activation. Male C57BL6 mice were subjected to myocardial I/R injury via 45 min. coronary ligation and release for the indicated times. Naoxintong (0.7 g/kg/day) and PBS were orally administrated for 2 weeks before surgery. Cardiac function assessed by echocardiography was significantly improved in the NXT group compared to PBS group at day 2 after myocardial I/R. NLRP3 inflammasome activation is crucially involved in the initial inflammatory response after myocardial I/R injury, leading to cleaved caspase-1, mature interleukin (IL)-1β production, accompanying by macrophage and neutrophil infiltration. The cardioprotective effect of NXT was associated with a diminished NLRP3 inflammasome activation, decreased pro-inflammatory macrophage (M1 macrophages) and neutrophil infiltration after myocardial I/R injury. In addition, serum levels of IL-1β, indicators of NLRP3 inflammasome activation, were also significantly suppressed in the NXT treated group after I/R injury. Naoxintong exerts cardioprotive effects at least partly by suppression of NLRP3 inflammasome activation in this I/R injury model.
脑心通(NXT)是一种中药标准化产品,由包括丹参、当归、黄芪在内的16种不同的传统中草药提取而成。脑心通在治疗缺血性心脏病方面具有临床疗效。含吡咯结构域的核苷酸结合寡聚化结构域样受体3(NLRP3)炎性小体与心肌缺血/再灌注(I/R)损伤密切相关。在此,我们提出脑心通可能通过抑制NLRP3炎性小体激活来减轻心肌I/R损伤。雄性C57BL6小鼠通过冠状动脉结扎45分钟并在指定时间松开以造成心肌I/R损伤。在手术前2周口服给予脑心通(0.7 g/kg/天)和磷酸盐缓冲液(PBS)。与PBS组相比,在心肌I/R后第2天,通过超声心动图评估的心脏功能在脑心通组中显著改善。NLRP3炎性小体激活在心肌I/R损伤后的初始炎症反应中起关键作用,导致半胱天冬酶-1裂解、成熟白细胞介素(IL)-1β产生,并伴有巨噬细胞和中性粒细胞浸润。脑心通的心脏保护作用与心肌I/R损伤后NLRP3炎性小体激活减弱、促炎性巨噬细胞(M1巨噬细胞)和中性粒细胞浸润减少有关。此外,在I/R损伤后,脑心通治疗组中作为NLRP3炎性小体激活指标的IL-1β血清水平也显著受到抑制。在这个I/R损伤模型中,脑心通至少部分地通过抑制NLRP3炎性小体激活发挥心脏保护作用。