基于HMGB1/TLR4/NF-κB信号通路探讨忍冬苷对脓毒症肝损伤大鼠的影响.

Objective: To investigate the effect of lonicerin on septic liver injury in rats based on the high mobility group protein B1 (HMGB1)/Toll-l-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway. Methods: 60 male SD rats were divided into model group, control group, positive control group (dexamethasone 10 mg/kg), lonicerin low dose (7.5 mg/kg), lonicerin middle dose (15 mg/kg), lonicerin high dose (30 mg/kg) groups, each group had 10 rats. The cecal ligation and puncture method was used to establish a rat sepsis model. After the experiment, the rats were anesthetized and blood was collected to prepare serum, and the superoxide Dismutase(SOD) activity and the contents of malondialdehyde(MDA), interleukin-6(IL-6), tumor necrosis factor α(TNF-α), interleukin-10(IL-10) in the serum were detected. The liver tissues were separated and weighed, the liver index was calculated, one part was used for HE staining to observe the pathological changes of liver tissue, and the other part was used to prepare tissue homogenate to detect the activities of liver function indexes alanine transaminase(ALT), aspartate Transaminase(AST) and the protein expression of HMGB1,TLR4 and NF-κB in the tissue. Results: Compared with the control group, the serum MDA, TNF-α, IL-6 contents, liver index, and liver tissue AST, ALT activity, HMGB1, TLR4 and NF-κB protein expression were increased significantly in the model group(P<0.05), the SOD activity and IL-10 content decreased significantly (P<0.05). Obvious lesions appeared in liver tissue, hepatocytes were edema and degeneration, and a large number of inflammatory cells infiltrated. Compared with the model group, the serum MDA, TNF-α, IL-6 contents, liver index, and liver tissue AST, ALT activity, HMGB1, TLR4, and NF-κB protein expression in the positive control group and the lonicerin each dose groups decreased significantly(P<0.05), the SOD activity and IL-10 content increased significantly (P<0.05). The lesions and edema were still seen in the lonicerin low and middle dose groups, but the lesions were alleviated. The liver cell structure of the positive control group and the lonicerin high dose group tended to be normal, and no lesions were found. Compared with the positive control group, the serum MDA, TNF-α, IL-6 contents, liver index, and liver tissue AST, ALT activity, HMGB1, TLR4, and NF-κB protein expression in the lonicerin low and middle dose groups increased significantly (P<0.05), the SOD activity and IL-10 content reduced significantly(P<0.05). There were no significant differences in the above indicators in the lonicerin high dose group (P>0.05). Conclusion: Lonicerin can down-regulate the HMGB1/TLR4/NF-κB signaling pathway, reduce inflammation reaction and oxidative stress, improve liver function, and play a protective effect on septic liver injury. [ABSTRACT FROM AUTHOR]