Department of Emergency, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, Jiangsu, China.
Department of Gastroenterological Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, Jiangsu, China.
J Cell Biochem. 2020 Apr;121(4):2994-3004. doi: 10.1002/jcb.29556. Epub 2019 Nov 11.
Sepsis-induced myocardial dysfunction (SIMD) causes high mortality in seriously ill patients. Ginsenoside Rg1 has been proven to have effective anti-inflammatory and antiapoptotic properties. However, the specific role of Rg1 in SIMD and the molecular mechanism remain unclear. Hence, we aimed to investigate the latent effects of ginsenoside Rg1 against SIMD and explore its underlying mechanisms. Male C57BL/6J mice and neonatal rat cardiomyocytes (NRCMs) were used as in vivo and in vitro models, respectively. Western blot analysis was used to detect the level of protein expression, and reverse transcription polymerase chain reaction was conducted to determine the messenger RNA expression of inflammatory factors. The terminal deoxynucleotidyl transferase-mediated nick end labeling assay and flow cytometry were used to determine the apoptosis rate. Echocardiography was performed to assess cardiac function. The results showed that Rg1 improved cardiac function and attenuated lipopolysaccharide (LPS)-induced apoptosis and inflammation in mice. In addition, in NRCMs, Rg1 downregulated the expression of LPS-induced inflammatory cytokines and reversed the increased expression of Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB), and NOD-like receptor 3 (NLRP3). In addition, treatment with TLR4 small interfering RNA (siRNA), a p-NF-κB inhibitor, or NLRP3 siRNA suppressed LPS-induced apoptosis and inflammation. In conclusion, Rg1 can attenuate LPS-induced inflammation and apoptosis both in NRCMs and septic mice and restore impaired cardiac function. Moreover, Rg1 may exert its effect via blocking the TLR4/NF-κB/NLRP3 pathway.
脓毒症诱导的心肌功能障碍（SIMD）导致重病患者死亡率居高不下。已证实人参皂苷 Rg1 具有有效的抗炎和抗凋亡作用。然而，Rg1 在 SIMD 中的具体作用及其分子机制尚不清楚。因此，我们旨在研究人参皂苷 Rg1 对 SIMD 的潜在作用，并探讨其潜在机制。雄性 C57BL/6J 小鼠和新生大鼠心肌细胞（NRCMs）分别用作体内和体外模型。采用 Western blot 分析检测蛋白表达水平，逆转录聚合酶链反应检测炎症因子的信使 RNA 表达。末端脱氧核苷酸转移酶介导的缺口末端标记法和流式细胞术检测细胞凋亡率。超声心动图评估心功能。结果表明，Rg1 改善了心脏功能，并减轻了 LPS 诱导的小鼠凋亡和炎症。此外，在 NRCMs 中，Rg1 下调了 LPS 诱导的炎症细胞因子的表达，并逆转了 Toll 样受体 4（TLR4）、核因子-κB（NF-κB）和 NOD 样受体 3（NLRP3）的表达增加。此外，用 TLR4 小干扰 RNA（siRNA）、p-NF-κB 抑制剂或 NLRP3 siRNA 处理可抑制 LPS 诱导的凋亡和炎症。总之，Rg1 可减轻 LPS 诱导的 NRCMs 和脓毒症小鼠的炎症和凋亡，并恢复受损的心脏功能。此外，Rg1 可能通过阻断 TLR4/NF-κB/NLRP3 通路发挥作用。
