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

Author: Cao WB, Du YQ, Gao LY, Che NC, Zhang QY, Fu XW, Luo JJ, Wang RB
Page: 371

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 in the experimental group were pretreated with TAA at dose of 12 mg/kg lasting 8 weeks, and from 9th week to 12th week, with TAA at concentration of 36 mg/kg. During the 9th week to 12th 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 mL/kg) group and QDD (5.95 g/kg) group, orally once per day respectively. At the 12th week, the content of serum alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), endotoxin (ET) and tumor necrosis factor a (TNF-a) 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.

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