Cardiology Department, the First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China; Emergency Department, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China.
Emergency Department, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China.
Chin J Nat Med. 2020 Mar;18(3):226-233. doi: 10.1016/S1875-5364(20)30025-X.
Shenfu injection (SFI), a Chinese medicinal product, shows potent efficacy in treating sepsis. The aim of the present study was to clarify the protective effects of SFI against lipopolysaccharide (LPS)-induced myocardial inflammation and apoptosis. Experiments were carried out in Sprague-Dawley (SD) rats treated with LPS or LPS + SFI, and in H9C2 cardiomyocytes. The sepsis-associated myocardial inflammation and apoptosis was induced by the intraperitoneal injection of LPS (20 mg·kg). SFI attenuated the increased expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β induced by LPS both in serum and heart. In LPS group, cell viability was reduced, and reversed after SFI administration. LPS treatment increased the expression levels of cleaved-caspase 3 and Bax, and those of Bcl2 and Bcl2/Bax. These two trends were reversed by SFI administration. The expression levels of phosphorylated mitogen-activated protein kinase kinase (p-MEK) and phosphorylated extracellular regulated protein kinases (p-ERK) were increased by LPS, and reversed by SFI. MEK inhibitor U0126 attenuated the apoptosis induced by LPS. These results indicate that SFI could treat LPS-induced cardiac dysfunction. In conclusion, SFI attenuates the inflammation and apoptosis induced by LPS via downregulating the MEK and ERK signaling pathways.
参附注射液（SFI）是一种中药制剂，在治疗脓毒症方面具有强大的疗效。本研究旨在阐明 SFI 对脂多糖（LPS）诱导的心肌炎症和细胞凋亡的保护作用。实验在腹腔注射 LPS（20mg·kg）的 Sprague-Dawley（SD）大鼠和 H9C2 心肌细胞中进行。SFI 可减轻 LPS 诱导的血清和心脏中肿瘤坏死因子（TNF）-α和白细胞介素（IL）-1β表达的增加。在 LPS 组中，细胞活力降低，SFI 给药后得到逆转。LPS 处理增加了裂解型半胱天冬酶 3（cleaved-caspase 3）和 Bax 的表达水平，Bcl2 和 Bcl2/Bax 的表达水平也随之增加。SFI 给药逆转了这两种趋势。LPS 增加了丝裂原活化蛋白激酶激酶（MEK）和细胞外调节蛋白激酶（ERK）的磷酸化水平，SFI 也逆转了这一趋势。MEK 抑制剂 U0126 可减弱 LPS 诱导的细胞凋亡。这些结果表明，SFI 可通过下调 MEK 和 ERK 信号通路来治疗 LPS 诱导的心脏功能障碍。综上所述，SFI 通过下调 MEK 和 ERK 信号通路来减轻 LPS 诱导的炎症和细胞凋亡。
