Grade 2015, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, P.R. China.
Department of Intensive Care Unit, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China.
J Pharm Pharmacol. 2021 Jun 8;73(7):916-921. doi: 10.1093/jpp/rgaa033.
Acute lung injury (ALI) is the major complication of sepsis, and no effective treatment is available now. Recently, rosmarinic acid (RA), a water-soluble polyphenolic phytochemical, exerts a potential role on ALI with anti-inflammation, and antioxidant properties. However, there is still no evidence on its protective effect on cell apoptosis in sepsis. Here, we investigated the protective effect of RA in septic-associated mortality and lung injury based on apoptosis.
Male C57BL/6 mice were administered with lipopolysaccharide (LPS) (15 mg/kg, ip) to establish ALI mice model. Preteatment of RA (20 or 40 mg/kg, ip) was performed once daily for five consecutive days. The mortality was monitored for seven days after injection of LPS.
RA (40 mg/kg) significantly decreased mortality and alleviated septic-associated lung injury. Meanwhile, RA significantly reversed LPS induced decrease in serum T-aoc level and superoxide dismutase (SOD) activity, and increase in malondialdehyde (MDA) activity. Furthermore, RA pretreatment significantly inhibited lung cell apoptosis, as well as decreased p53 level in sepsis mice. Finally, the LPS induced activation of GRP78/IRE1α/JNK pathway was suppressed by RA pretreatment.
These findings indicated that RA could be beneficial to septic-associated lung injury through anti-apoptosis effect.
急性肺损伤（ALI）是脓毒症的主要并发症，目前尚无有效的治疗方法。最近，迷迭香酸（RA）作为一种水溶性多酚类植物化学物质，具有抗炎和抗氧化作用，对 ALI 具有潜在作用。然而，关于其在脓毒症细胞凋亡保护作用方面仍缺乏证据。本研究基于细胞凋亡探讨 RA 对脓毒症相关死亡率和肺损伤的保护作用。
雄性 C57BL/6 小鼠腹腔注射脂多糖（LPS）（15mg/kg）建立 ALI 小鼠模型。RA（20 或 40mg/kg，腹腔注射）预处理每天一次，连续五天。注射 LPS 后七天监测死亡率。
RA（40mg/kg）可显著降低死亡率并减轻脓毒症相关的肺损伤。同时，RA 可显著逆转 LPS 诱导的血清总抗氧化能力（T-aoc）水平和超氧化物歧化酶（SOD）活性下降，以及丙二醛（MDA）活性升高。此外，RA 预处理可显著抑制脓毒症小鼠的肺细胞凋亡，并降低 p53 水平。最后，RA 预处理可抑制 LPS 诱导的 GRP78/IRE1α/JNK 通路的激活。
这些发现表明，RA 通过抗细胞凋亡作用有益于脓毒症相关的肺损伤。
