Sinomenine attenuates septic-associated lung injury through the Nrf2-Keap1 and autophagy
Sinomenine attenuates septic-associated lung injury through the Nrf2-Keap1 and autophagy
复制标题
青藤碱通过 Nrf2-Keap1 和自噬减轻脓毒症相关肺损伤
DOI：
10.1111/jphp.13202
复制
发表时间：
2019-11-15
影响因子：
3.3
通讯作者：
Huang, Fengjie
中科院分区：
文献类型：
--
作者：
Wang, Wanqiu;Yang, Xiaoting;Huang, Fengjie
目的探讨青藤碱（SIN）对脓毒症急性肺损伤（ALI）的保护作用。方法腹腔注射脂多糖（LPS）前1h，用SIN处理小鼠。检测肺湿/干（W/D）比值、支气管肺泡灌洗液（BALF）中炎症水平、丙二醛（MDA）含量、超氧化物歧化酶（SOD）活性及炎性细胞因子的产生。Western blot和免疫组化检测核因子红细胞2样蛋白2（Nrf 2）和自噬相关蛋白的表达。另外，在用LPS处理前1h用SIN处理RAW 264.7细胞。检测炎性细胞因子、iNOS和COX 2。Western blot分析Nrf 2和自噬相关蛋白的表达。体内和体外实验发现，LPS显著增加了损伤程度、炎性细胞因子的产生和氧化应激。而SIN处理则显著抑制了这种增加。此外，SIN被发现在体内和体外上调Nrf 2和自噬相关蛋白的表达。结论SIN能有效减轻脓毒症相关性ALI，其机制可能与其通过Nrf 2和自噬途径抑制炎症和氧化应激有关。
Objectives Our present study focused on assessing whether Sinomenine (SIN) could attenuate sepsis-induced acute lung injury (ALI). Methods The mice were conditioned with SIN 1 h before intraperitoneal injection of lipopolysaccharide (LPS). Lung wet/dry (W/D) ratio, inflammatory level in bronchoalveolar lavage fluid (BALF), malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity and inflammatory cytokines production were detected. The expression of nuclear factor erythroid 2-like 2 (Nrf2) and autophagy-related proteins were detected by Western blot and immunohistochemical analyses. In addition, the RAW264.7 cells were treated with SIN 1 h before treatment with LPS. Inflammatory cytokines, iNOS and COX2 were detected. The expression of Nrf2 and autophagy-related proteins were explored by Western blot analysis. Key findings Experiments in vivo and in vitro discovered that LPS significantly increased the degree of injury, inflammatory cytokines production and oxidative stress. However, the increase was significantly inhibited by treatment of SIN. In addition, SIN was found to upregulate the expression of Nrf2 and autophagy-related proteins both in vivo and in vitro. Conclusions Our data suggested that SIN could attenuate septic-associated ALI effectively, probably due to the inhibition of inflammation and oxidative stress through Nrf2 and autophagy pathways.