| 张楠,张海骏,范艳艳.季德胜蛇药片治疗急性痛风性关节炎大鼠的机制研究[J].安徽医药,2025,29(2):253-257. |
| 季德胜蛇药片治疗急性痛风性关节炎大鼠的机制研究 |
| Mechanism of Jidesheng snake tablets in the treatment of rats with acute gouty arthritis |
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| DOI：10.3969/j.issn.1009-6469.2025.02.008 |
| 中文关键词: 急性痛风性关节炎 季德胜蛇药片 炎症因子 核转录因子 -κB 大鼠 |
| 英文关键词: Acute gouty arthritis Jidesheng snake tablet Inflammatory factor Nuclear transcription factor-κB Rat |
| 基金项目:南通市市级科技计划指导性项目( JCZ20201) |
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| 中文摘要: |
| 目的探究季德胜蛇药片治疗急性痛风性关节炎( AGA)大鼠的可能机制。方法 2022年 10月至 2023年 2月，选取 60只雄性 SD大鼠为研究对象，采用随机数字表法分为空白对照组、模型组、季德胜蛇药片组和依托考昔组，除空白对照组外其他大鼠均通过关节腔注射尿酸钠溶液构建 AGA大鼠模型，造模成功后 12 h，季德胜蛇药片组灌胃季德胜蛇药片 2.4 g·kg.1·d.1，依托考昔组灌胃依托考昔 3.125 mg·kg.1·d.1，均持续干预 7d，测量各组大鼠关节肿胀程度、步态行为学分级，并于末次干预 12 h后腹主动脉取血采用酶联免疫吸附法测量血清白细胞介素 -1β(IL-1β)、 IL-6、IL-10及肿瘤坏死因子( TNF-α)水平；麻醉处死大鼠后分离踝关节滑膜组织固定后制成切片 HE染色观察病理形态学特征，蛋白质印迹法检测滑膜组织中核转录因子 -κB p65(NF-κB p65)、 IL-1β、IL-6、IL-10、TNF-α蛋白表达水平。结果与空白对照组比较，模型组造模后 1、2、3d时关节肿胀度均升高，且步态行为学分级程度也升高( P<0.05)与模型组比较，季德胜蛇药片组与依托考昔组大鼠关节肿胀度均降低，步态行为学分级程度也有改善(P<0.05)。 HE染色结果显，示，模型组大鼠可见明显滑膜组织增生，充血水肿并伴有大量中性粒细胞及单核细胞等炎症细胞浸润，季德胜蛇药片干预后滑膜层细胞基本正常，轻微充血水肿，炎症细胞浸润程度降低，与依托考昔干预后情况基本一致。模型组大鼠血清 IL-1β、IL-6、TNF-α水平［(45.15±8.76)ng/L、(54.26±8.29)ng/L、(229.54±31.18)ng/L］均高于空白对照组大鼠［( 10.41±3.25)ng/L、(16.52±4.13)ng/L、(108.94±21.26)ng/L，P<0.05］，滑膜组织中 p-NF-κB p65/NF-κB p65、 IL-1β、IL-6、TNF-α蛋白表达( 1.98±0.32、1.34±0.12、1.20±0.18、1.30±0.11)均高于空白对照组大鼠( 0.32±0.07、0.18±0.03、0.28± 0.05、0.24±0.04，P<0.05)，血清、滑膜组织 IL-10水平和蛋白表达［(21.06±4.39)ng/L、0.72±0.09］均低于空白对照组大鼠［(43.15±7.24)ng/L、1.45±0.12，P<0.05］。与模型组大鼠比较，季德胜蛇药片组、依托考昔组大鼠血清 IL-1β、IL-6、TNF-α水平［季德胜蛇药片组分别为( 21.62±3.95)ng/L、(24.37±5.26)ng/L、(135.31±22.47)ng/L，依托考昔组分别为( 22.42±4.39)ng/L、(26.08±5.41)ng/ L、(139.42±21.35)ng/L］及滑膜组织中 p-NF-κB p65/NF-κB p65、IL-1β、IL-6、TNF-α蛋白表达均降低(季德胜蛇药片组分别为 0.72±0.14、0.64±0.09、0.73±0.10、0.56±0.07，依托考昔组分别为 0.69±0.13、0.57±0.07、0.68±0.13、0.58±0.08，均 P<0.05)，血清 IL-10水平和滑膜组织 IL-10蛋白表达升高［季德胜蛇药片组分别为( 38.15±5.25)ng/L、1.08±0.11，依托考昔组分别为( 36.97±6.12)ng/L、1.10±0.13，均 P<0.05］，季德胜蛇药片组与依托考昔组上述指标比较差异无统计学意义( P>0.05)。结论季德胜蛇药片能够明显改善急性痛风性大鼠关节症状，下调关节炎症反应，可能与抑制 NF-κB信号通路活化有关。 |
| 英文摘要: |
| 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 wererandomly 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 jointswelling and behavioral grading of gait were measured. At 12 h after the last intervention, the blood of abdominal aorta was collected todetect 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 wasincreased 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 edemaaccompanied 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, whichwas 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. |
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