Protective effect of gastrodin combined with celecoxib on cartilage injury in rats with knee osteoarthritis through TLR4/NF-κB signaling pathway
10.3760/cma.j.cn121382-20241030-00607
- VernacularTitle:天麻素联合塞来昔布通过TLR4/NF-κB信号通路对膝骨关节炎大鼠软骨损伤的保护作用
- Author:
Heng WANG
1
;
Zhibin LI
;
Xiaoxia GUO
;
Chenxin YI
;
Xiaoming ZHAO
;
Zhi CHEN
Author Information
1. 陕西中医药大学附属医院急救中心，咸阳 712000
- Keywords:
Knee osteoarthritis;
Gastrodin;
Celecoxib;
Toll-like receptor 4;
Nuclear factor-κB
- From:
International Journal of Biomedical Engineering
2024;47(6):560-567
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the protective effect of gastrodin combined with celecoxib on cartilage injury in rats with knee osteoarthritis through Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway.Methods:Knee osteoarthritis rat models were established by the modified Hulth method. According to the random number table method, rat models were randomly divided into the model group, the gastrodin group, the celecoxib group, and combined group with 10 rats in each group. An additional 10 healthy rats were selected and served as the control group. The rats in the gastrodin group received 50 mg/kg gastrodin by intraperitoneal injection. The rats in the celecoxib group received 4 mg/kg celecoxib by gavage. In the combined group, the rats received 50 mg/kg gastrodin by intraperitoneal injection, followed by 4 mg/kg celecoxib by gavage. Rats in both the control group and the model group received intraperitoneal injections and gavage of an equal volume of normal saline, which were administered once a day for 21 d. The symptoms of joint pain, the degree of joint swelling, the width of the knee joint, the joint function, and the cartilage thickness of the rats in all groups were compared. The expression level of proinflammatory factors, including interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-17 (IL-17), and tumor necrosis factor-α (TNF-α), in cartilage was determined by enzyme-linked immunosorbent assay (ELISA). The relative expression levels of TLR4 and NF-κB proteins and genes in cartilage were detected by Western blotting and real-time reverse transcription-PCR (RT-qPCR), respectively.Results:The mechanical pain threshold [(19.77±2.05) g] and thermal pain threshold [(10.06±1.54) s] in the combined group were higher than those in the model, gastrodin, and celecoxib groups [(5.27±1.23), (11.27±1.55), and (12.85±1.62) g for mechanical pain threshold, and (4.26±0.84), (7.21±1.31), (7.36±1.15) s for thermal pain threshold], respectively, and the differences were statistically significant (all P<0.05). The degree of joint swelling [(8.23±1.05)%], knee joint width [(5.19±0.23) mm], and gait score [(0.56±0.22) points] in the combined group were all lower than those in the model, gastrodin, and celecoxib groups [(38.26±6.77)%, (17.76±2.18)%, and (17.23±2.44)% for joint swelling degree, (9.86±1.16), (6.43±0.54), and (6.23±0.78) mm for knee joint width, and (2.25±0.47), (1.26±0.23), and (1.25±0.14) points for gait score], respectively, and the differences were statistically significant (all P<0.05). The levels of IL-1β [(53.37±10.26) pg/ml], IL-6 [(51.26±6.22) pg/ml], IL-17 [(136.33±8.67) pg/ml], and TNF-α [(62.36±12.03) pg/ml] in the cartilage tissue of rats in the combined group were all lower than those in the model, gastrodin, and celecoxib groups [IL-1β: (112.33±18.56), (76.55±12.03), (72.69±14.88) pg/ml; IL-6: (90.33±12.06), (69.23±8.09), (65.42±7.01) pg/ml; IL-17: (215.66±20.22), (165.33±14.69), (160.36±15.55) pg/ml; TNF-α: (138.09±18.26), (89.66±15.36), (84.03±14.77) pg/ml], respectively, and the differences were statistically significant (all P<0.05). Compared with the model group, the cartilage thickness of rats in the gastrodin, celecoxib, and combined groups [(945.86±63.87), (962.75±129.14), (1 410.48±60.42) μm] were increased, and the differences were statistically significant (all P<0.05). The relative expression levels of TLR4 and NF-κB proteins [(2.13±0.88), (2.01±0.35)] and mRNAs [(1.48±0.11), (1.73±0.12)] in the cartilage tissue of rats in the combined group were all lower than those in the model group [TLR4, NF-κB proteins: (5.26±0.95), (4.32±0.71); mRNAs: (4.37±0.43), (5.27±0.48)], the gastrodin group [TLR4, NF-κB proteins: (3.22±0.75), (3.16±0.33); mRNAs: (2.53±0.21), (3.52±0.22)], and the celecoxib group [TLR4, NF-κB proteins: (3.26±0.61), (3.19±0.30); mRNAs: (2.55±0.24), (3.55±0.31)], and the differences were statistically significant (all P<0.05). Conclusions:Gastrodin combined with celecoxib can inhibit the symptoms of joint pain and inflammation in rats with knee osteoarthritis by inhibiting the activation of TLR4/NF-κB signaling, and alleviate the cartilage injury.
