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Effects of Propofol on Liver Function and HMGB1/TLR4 Signaling Pathway in with Carbon Dioxide Pneumoperitoneum Rats |
AI Ling, XU Hui, CHEN Hao |
Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Hubei Wuhan 430030, China |
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Abstract Objective: To investigate the effects of propofol on liver function and high mobility group protein box 1 (HMGB1) / Toll-like receptor 4 (TLR4) pathway in with carbon dioxide pneumoperitoneum rats. Methods: The pneumoperitoneum model rats were established by setting the pneumoperitoneum pressure of 20 mmHg for 2 hours, the successful model rats were randomly divided into pneumoperitoneum group, propofol low (5mg/kg), medium (10mg/kg), high (20mg/kg) dose group and positive control group (biphenyl diester, 25mg/kg), with 10 rats in each group; and then a sham operation group (10 healthy rats) were constructed and operated by modeling without pneumoperitoneum. Two hours after operation, the sham operation group and pneumoperitoneum group were injected with normal saline intraperitoneally, propofol groups were injected intraperitoneally with propofol solution of corresponding dose, and the positive control group was given bifendate solution by gavage. Ten hours after the administration, the abdominal aortic blood and liver tissue were taken, and the liver function indexes serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), liver tissue inflammatory factors interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) levels were detected by enzyme-linked immunosorbent assay. Hematoxylin eosin staining was used to detect the morphological changes of liver tissue. The protein expression of HMGB1, TLR4, monocyte chemotactic protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1) and interferon-γ (IFN-γ) in liver tissue were detected by western blot.Results: Compared with those in sham operation group, the degeneration and necrosis of hepatocytes were serious in pneumoperitoneum group, the levels of serum AST, ALT, liver tissue IL-6, TNF-α, and the protein expression of HMGB1, TLR4, MCP-1, ICAM-1 and IFN-γ were higher (P<0.05). Compared with those in pneumoperitoneum group, the degeneration and necrosis of hepatocytes in the low, medium and high dose propofol groups and the positive control group were alleviated, the levels of serum AST, ALT, liver tissue IL-6, TNF-α, and the protein expression of HMGB1, TLR4, MCP-1, ICAM-1 and IFN-γ were lower (P<0.05), and the higher the dose of propofol, the more obvious the improvement effect (P<0.05); the improvement effect of propofol high dose group on liver injury was similar to that of positive control group (P>0.05).Conclusion: Propofol can inhibit the activation of HMGB1/TLR4 pathway, reduce the expression of inflammatory factors and chemokines in liver tissue, alleviate liver injury and improve liver function in rats with pneumoperitoneum.
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