Abstract: Objective To explore the effect and mechanism of isoliensinine on lipopolysaccharide（LPS）-induced acute lung injury. Methods C57BL6J mice were randomly divided into four groups：control group,model group（LPS group）,isoliensinine group,LPS+isoliensinine group,12 animals in each group. The mice were treated with intratracheal injection of 200 μg LPS to induce acute lung injury model. The H&E staining,lung wet weight/dry weight ratio and inflammation index were used to evaluate the degree of acute pneumonia. ELISA kit was used to detect pro-inflammatory factors,tumor necrosis factor TNF-α（TNF-α）,interleukin-1（IL-1） and interleukin-6（IL-6） levels. The kits were used to detect reactive oxygen species（ROS）,malondialdehyde （MDA）,superoxide dismutase（SOD） and glutathione reductase（Gpx） levels/activity. The Western blot was used to detect changes in related signal molecules. Results H&E staining showed that the inflammatory infiltration of the lung tissues in the LPS group increased,and the wet weight/dry weight ratio（4.09±0.55vs5.73±0.55） and inflammation index（0.36±0.11vs4.25±0.53） of the lungs were higher than those of the control group. The ELISA results showed that the levels of TNF-α[（45.93±8.08）vs （198.71±37.85）pg/mL],IL-1[（111.31±6.54）vs（151.27±18.39）pg/mL] and IL-6[（50.15±11.72）vs（468.07±41.23）pg/mL] in the lung tissues of the LPS group were significantly higher than those of the control group,the content of ROS（1.00±0.23vs4.73±0.39）and MDA（1.00±0.09vs4.53±0.07） in the LPS group was higher than those of the control group,and the activities of SOD2 [（2.07±0.11）vs（0.74±0.22）U/mg] and Gpx[（188.03±16.64）vs（69.59±13.51）μmol/g] were significantly lower than those of the control group. The lung wet weight/dry weight ratio（4.88±0.39）,inflammation index（3.05±0.49）,inflammatory factors,and contents of ROS（2.31±0.32） and MDA（2.97±0.47） in LPS+isoliensinine group were lower than those in LPS group,while the activities of SOD2[（1.65±0.13）U/mg] and Gpx[（143.61±24.21）μmol/g] were significantly higher than those of LPS group. The Western blot results showed that toll like receptor 4（TLR4） and phosphorylated nuclear factor-κB（NF-κB） of lung tissues in LPS group were significantly increased,while the expression of TLR4 and phosphorylated NF-κB of LPS+isoliensinine group was lower than those of LPS group. Conclusion The isoliensinine can reduce acute lung injury induced by lipopolysaccharide by inhibiting TLR4. The isoliensinine may be a new treatment for lung injury.

Key words: Isoliensinine, Llipopolysaccharide, Acute lung injury, Toll-like receptor 4