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棕矢车菊素调节 AMPK/NLRP3 信号通路对骨关节炎大鼠炎性
损伤的影响
Δ
1*
2 #
魏 超 ,于 江 ,盛关云 ,蔡 毅(1.江汉大学附属医院/武汉市第六医院疼痛科,武汉 430015;2.江汉
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大学附属医院/武汉市第六医院骨外科,武汉 430015;3. 柳州市中医医院综合骨科,广西 柳州 545000;
4.武汉市中心医院疼痛科,武汉 430014)
中图分类号 R965;R285 文献标志码 A 文章编号 1001-0408(2025)04-0421-06
DOI 10.6039/j.issn.1001-0408.2025.04.06
摘 要 目的 探讨棕矢车菊素激活腺苷一磷酸活化的蛋白激酶(AMPK)/NOD样受体蛋白3(NLRP3)信号通路对大鼠骨关节炎
(OA)的影响。方法 大鼠随机分为 OA 组、棕矢车菊素(33.33 mg/kg)组、AMPK 抑制剂(Compound C,20 mg/kg)组、棕矢车菊素
(33.33 mg/kg)+Compound C(20 mg/kg)组和假手术组,每组12只。除假手术组外,其余各组大鼠均通过改良Hulth法建立OA模
型。建模成功后,各组大鼠灌胃相应剂量的棕矢车菊素或生理盐水,且腹腔注射相应剂量的Compound C或生理盐水,每天1次,
持续8周。末次给药24 h后,检测各组大鼠膝关节肿胀度;观察大鼠膝关节软骨组织的病理并进行Mankin评分;检测大鼠膝关节
软骨组织中肿瘤坏死因子α(TNF-α)、白细胞介素18(IL-18)、IL-6水平,胶原蛋白Ⅱ(collagen Ⅱ)、聚集蛋白聚糖(ACAN)、血小板
反应蛋白解整合素金属肽酶 5(ADAMTS5)蛋白表达,以及磷酸化 AMPK(p-AMPK)、AMPK、NLRP3、裂解的胱天蛋白酶 1
(cleaved-caspase-1)、裂解的 IL-1β(cleaved-IL-1β)蛋白表达。结果 与 OA 组比较,棕矢车菊素组大鼠软骨组织缺损现象有所缓
解,软骨基质染色加深,软骨细胞数量增多;膝关节肿胀度、Mankin 评分和膝关节软骨组织中 TNF-α、IL-18、IL-6 水平以及
ADAMTS5、NLRP3、cleaved-caspase-1、cleaved-IL-1β蛋白表达水平均显著降低或下调,collagen Ⅱ、ACAN蛋白表达水平和AMPK
磷酸化均显著升高或上调(P<0.05)。Compound C显著逆转了棕矢车菊素对OA大鼠上述指标的改善作用(P<0.05)。结论 棕
矢车菊素可能通过调控AMPK/NLRP3信号通路来抑制OA大鼠炎症反应及细胞外基质降解。
关键词 棕矢车菊素;AMPK/NLRP3信号通路;骨关节炎;炎症;细胞外基质
Effects of jaceosidin on inflammatory injury in osteoarthritis rats by regulating AMPK/NLRP3 signaling
pathway
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WEI Chao ,YU Jiang ,SHENG Guanyun ,CAI Yi(1. Dept. of Pain, Jianghan University Affiliated Hospital/
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Wuhan Sixth Hospital, Wuhan 430015, China;2. Dept. of Orthopedic Surgery, Jianghan University Affiliated
Hospital/Wuhan Sixth Hospital, Wuhan 430015, China;3. Dept. of Orthopaedics, Liuzhou Hospital of
Traditional Chinese Medicine, Guangxi Liuzhou 545000, China;4. Dept. of Pain, Wuhan Central Hospital,
Wuhan 430014, China)
ABSTRACT OBJECTIVE To investigate the effects of jaceosidin on osteoarthritis (OA) of rats by regulating adenosine
monophosphate-activated protein kinase (AMPK)/NOD-like receptor protein 3 (NLRP3) pathway. METHODS Rats were randomly
separated into OA group, jaceosidin group (33.33 mg/kg), AMPK inhibitor (Compound C, 20 mg/kg) group, jaceosidin (33.33
mg/kg)+Compound C (20 mg/kg) group, and sham operation group, with 12 rats in each group. Except for the sham operation
group, the OA model was induced with modified Hulth method in all other groups. After successful modeling, they were given a
relevant dose of jaceosidin or normal saline intragastrically, and Compound C or normal saline intraperitoneally, once a day, for
consecutive 8 weeks. Twenty-four h after the last medication, the degree of knee joint swelling in rats from each group was
measured. The pathological changes of the articular cartilage tissue in the knee joints, and the Mankin score were assessed. The
levels of tumor necrosis factor-α (TNF-α), interleukin-18 (IL-18), and IL-6, as well as the protein expressions of collagen Ⅱ,
aggrecan (ACAN), and a disintegrin and metalloproteinase with thrombospondin 5 (ADAMTS5), phosphorylated AMPK (p-AMPK),
AMPK, NLRP3, cleaved-caspase-1, and cleaved-IL-1β were detected in the articular cartilage tissue of rats’ knees. RESULTS
Compared with OA group, the cartilage tissue defect of jaceosidin group was relieved, the cartilage matrix staining was deepened,
and the number of chondrocytes was increased. Knee swelling,
Δ 基金项目 湖北省自然科学基金项目(No.2022CFB185) Mankin score, the levels of TNF- α, IL-18 and IL-6, and
*第一作者 主治医师,硕士。研究方向:骨关节疾病基础研究。
protein expressions of ADAMTS5, NLRP3, cleaved-caspase-1
电话:027-82410046。E-mail:beca31@163.com
# 通信作者 主治医师,硕士。研究方向:骨关节及脊柱疾病基础 and cleaved-IL-1β in knee cartilage were significantly decreased
研究。电话:027-82441142。E-mail:xua9gae@163.com or down-regulated. Protein expressions of collagen Ⅱ, ACAN
中国药房 2025年第36卷第4期 China Pharmacy 2025 Vol. 36 No. 4 · 421 ·