Lipopolysaccharide/Toll-like receptor 4 signaling pathway involved Qingdu decoction treating severe liver injury merging with endotoxemia

• Published in: 中医杂志：英文版 2017-06, Vol.37 (3), p.371-377
• Main Author: Cao Wubing Du Yuqiong Gao Lianyin Che Niancong Zhang Qiuyun Fu Xiuwen Luo Jiajia Wang Rongbing
• Format: Article
• Language: English
• Subjects: Toll样受体4; Wistar大鼠; 信号通路; 全自动生化分析仪; 内毒素血症; 肝损伤; 脂多糖; 透射电子显微镜
• ISSN: 0255-2922

OBJECTIVE： To investigate the protective effects and underlying mechanism of Qingdu decoction（QDD） on experimental rats with severe liver injury induced by thioacetamide（TAA）.METHODS： A total of 40 Wistar rats were randomly divided into normal group（n = 10） and experimental group（n = 30）. Rats were administrated the same content of saline in normal group. The rats inthe experimental group were pretreated with TAA at dose of 12 mg/kg lasting 8 weeks, and from 9th week to 12 th week, with TAA at concentration of 36mg/kg. During the 9th week to 12 th week period,the rats were randomly divided into three subgroups（n = 10 each） simultaneously based on the treatment categories： model group, lactulose（LA,3.5 m L/kg） group and QDD（5.95 g/kg） group, orally once per day respectively. At the 12 th week, the content of serum alanine transaminase（ALT）, aspartate transaminase（AST）, total bilirubin（TBIL）, endotoxin（ET） and tumor necrosis factor α（TNF-α） was detected by automatic biochemical analyzer. The plasma prothrombin time（PT）, prothrombin time-international normalized ratio（PTR） and prothrombin time activity（PTA） were measured by automatic coagulation analyzer. The level of lipopolysaccharide（LPS）-binding protein（LBP）, cluster differentiation 14（CD14） and Toll-like receptor 4（TLR4） expressions was measured by both western blot（WB） and real-time polymerase chain reaction（real-time PCR）.RESULTS： Compared with the model group, hepatic morphology in the QDD group was improved under light microscope and transmission electron microscope; at the same time, the contents of serum ALT, AST, TBIL, ET and TNF-α, and level of LBP, CD14 and TLR4 expressions in liver tissues were significantly decreased compared with the model group（P 〈 0.05）, while PTA in the QDD group was enhanced（P 〈 0.05）.CONCLUSION： QDD has the functional effect on improving the injured liver through inhibiting the LPS/TLR4 signaling pathway thus decreasing the level of the inflammatory medicators.