Objective To investigate the mechanism by which Xinqian Ganjie Decoction alleviates inflammatory responses in rat model of chronic rhinosinusitis by inhibiting the activation of the toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) signaling pathway.
Methods Thirty-two 4-week-old healthy male Sprague-Dawley (SD) rats were randomly divided into model group (intragastric administration of 1.5 mL normal saline) and low-, medium-, and high-dose groups (intragastric administration of 0.75, 1.50, and 3.00 mL/kg Xinqian Ganjie Decoction, respectively), with 8 rats in each group. Another 8 healthy rats were randomly selected as control group (intragastric administration of 1.5 mL normal saline). A rat model of chronic rhinosinusitis was established in the model group and the low-, medium-, and high-dose groups by placing expanded cotton pledgets in the nasal cavity and injecting Staphylococcus aureus suspension. After successful model establishment, rats in each group were treated by intragastric administration for 14 consecutive days. The number of sneezes and nose scratches in each group was observed. Olfactory function changes in rats were assessed using an olfactory function test. Histopathological changes in nasal mucosa were detected by hematoxylin-eosin (HE) staining. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in nasal mucosa were measured by enzyme-linked immunosorbent assay (ELISA). The expression levels of proteins related to the TLR4/NF-κB signaling pathway were detected by western blot.
Results Compared with the control group, rats in the model, low-, medium-, and high-dose groups showed increased number of sneezes and nose scratches. Compared with the model group, rats in the medium- and high-dose groups exhibited decreased number of sneezes and nose scratches. The differences among these groups were all statistically significant (P < 0.01). Before treatment, the time taken by rats to find food pellets in the control group was longer than that in the other groups (P < 0.01). After treatment, rats took longer to find food pellets in the model group compared with the control group, while rats in the low-, medium-, and high-dose groups took less time than the model group, with a decreasing trend in time as the dose increased. The differences among these groups were all statistically significant (P < 0.01). HE staining results showed that the nasal mucosa of rats in the control group was intact with no inflammatory cell infiltration. Compared with the control group, the nasal mucosa of rats in the model group was significantly thickened with a large number of inflammatory cell infiltrations. Compared with the model group, the nasal mucosa thickening in rats of the medium- and high-dose groups was alleviated, with only a small amount of inflammatory cell infiltration observed. The levels of TNF-α, IL-1β, and IL-6 in the nasal mucosa of rats in the model group were higher than those in the control group. Compared with the model group, the levels of TNF-α, IL-1β, and IL-6 in the medium- and high-dose groups were decreased. The above differences among these groups were all statistically significant (P < 0.01). The expression levels of TLR4 and p-p65 NF-κB proteins in the nasal mucosa of rats in the model group were higher than those in the control group. Compared with the model group, the expression levels of TLR4 and p-p65 NF-κB in the medium- and high-dose groups were decreased. The differences among these groups were all statistically significant (P < 0.01).
Conclusion Xinqian Ganjie Decoction may reduce the release of TNF-α, IL-1β, and IL-6 by inhibiting the activation of the TLR4/NF-κB signaling pathway, thereby alleviating inflammatory responses and improving symptoms in a rat model of CRS.
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