Mechanism of Jidesheng snake tablets in the treatment of rats with acute gouty arthritis
Objective To explore the possible mechanism of Jidesheng snake tablets in the treatment of rats with acute gouty arthritis(AGA).Methods A total of 60 male SD rats were enrolled as the research objects from October 2022 to February 2023,which were randomly assigned into blank control group,model group,Jidesheng snake tablets group and etoricoxib group.Except blank control group,rats were given intra-articular injection of sodium urate solution to construct models of rats with AGA in the other groups.At 12 h after successful modeling,Jidesheng snake tablets group was given intragastric administration of Jidesheng snake tablets(2.4 g·kg-1·d-1),while etoricoxib group was given intragastric administration of etoricoxib(3.125 mg·kg-1·d-1),and both for 7 d.The severity of joint swelling and behavioral grading of gait were measured.At 12 h after the last intervention,the blood of abdominal aorta was collected to detect levels of serum interleukin-1β(IL-1β),IL-6,IL-10 and tumor necrosis factor α(TNF-α)by enzyme-linked immunosorbent assay.After the rats were killed under anesthesia,synovial tissues of ankle joints were made into slices to observe pathomorphological charac-teristics by HE staining.The expression levels of nuclear transcription factor κB p65(NF-κB p65),IL-1β,IL-6,IL-10 and TNF-α pro-tein in synovial tissues were detected by Western blotting.Results Compared with blank control group,severity of joint swelling was increased in model group at 1 d,2 d and 3d after modeling,and behavioral grading of gait was also increased(P<0.05).Compared with model group,severity of joint swelling was decreased,and behavioral grading of gait was improved in Jidesheng snake tablets group and etoricoxib group(P<0.05).The results of HE staining showed that there was obvious synovial tissue hyperplasia,hyperemia and edema accompanied by inflammatory cells(neutrophils,monocytes)infiltration in model group.After intervention with Jidesheng snake tab-lets,synovial cells were basically normal.There was mild hyperemia and edema,and inflammatory cells infiltration was reduced,which was basically consistent with the situation after etoricoxib intervention.In model group,the levels of serum IL-1β,IL-6 and TNF-α were(45.15±8.76)ng/L,(54.26±8.29)ng/L and(229.54±31.18)ng/L,higher than those in blank control group[(10.41±3.25)ng/L,(16.52±4.13)ng/L,(108.94±21.26)ng/L;P<0.05];expressions of p-NF-κB p65/NF-κB p65,IL-1β,IL-6 and TNF-α proteins in synovi-al tissues were(1.98±0.32,1.34±0.12,1.20±0.18 and 1.30±0.11),higher than those in blank control group(0.32±0.07,0.18±0.03,0.28±0.05,0.24±0.04;P<0.05);IL-10 level and protein expression in serum and synovial tissues were(21.06±4.39)ng/L and 0.72±0.09,lower than those in blank control group[(43.15±7.24)ng/L,1.45±0.12;P<0.05].Compared with model group,levels of serum IL-1β,IL-6 and TNF-α were decreased in Jidesheng snake tablets group and etoricoxib group[(21.62±3.95)ng/L,(24.37±5.26)ng/L,(135.31±22.47)ng/L;(22.42±4.39)ng/L,(26.08±5.41)ng/L,(139.42±21.35)ng/L],expressions of p-NF-κB p65/NF-κB p65,IL-1β,IL-6 and TNF-α proteins in synovial tissues were decreased[Jidesheng snake tablets group:(0.72±0.14,0.64±0.09,0.73±0.10,0.56±0.07;etoricoxib group:0.69±0.13,0.57±0.07,0.68±0.13,0.58±0.08;P<0.05),and serum IL-10 level and protein expression in synovial tis-sues were increased[Jidesheng snake tablets group:(38.15±5.25)ng/L,1.08±0.11;etoricoxib group:(36.97±6.12)ng/L,1.10±0.13;P<0.05].There was no significant difference in the above indexes between Jidesheng snake tablets group and etoricoxib group(P>0.05).Conclusion Jidesheng snake tablets can significantly improve joint symptoms and down-regulate joint inflammatory response in rats with acute gouty arthritis,which may be related to inhibiting activation of NF-κB signaling pathway.