| 九味健步饮介导HMGB1/RAGE/PI3K/Akt信号通路对膝骨关节炎大鼠氧化应激和炎性损伤的影响 |
| 投稿时间：2025-03-18 修订日期：2025-08-02 点此下载全文 |
| 引用本文：赵一龙,张兆剑,王国威,胡俊雄,郑全伟,刘建航.九味健步饮介导HMGB1/RAGE/PI3K/Akt信号通路对膝骨关节炎大鼠氧化应激和炎性损伤的影响[J].医学研究杂志,2025,54(8):48-55 |
| DOI：
10.11969/j.issn.1673-548X.2025.08.009 |
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| 基金项目:国家自然科学基金资助项目(82160848) |
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| 中文摘要:目的 讨九味健步饮通过高迁移率族蛋白B1(high mobility group box-1 protein,HMGB1)/晚期糖基化终末产物受体(receptor for advanced glycation endproducts,RAGE)/磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)/蛋白激酶B(protein kinase B, Akt)信号通路对膝骨关节炎大鼠氧化应激和炎性损伤的影响。方法 将60只大鼠按照随机数字表法随机分为6组,即空白对照组,模型组,阳性药物组,九味健步饮低、中、高剂量组,每组各10只。除空白对照组外,其余组构建膝骨关节炎模型并给予相应处理。观察膝关节直径、机械疼痛和热痛阈值变化。苏木精-伊红染色和番红O/固绿染色评估软骨组织病理变化。检测各组膝关节软骨组织氧化应激标志物和炎性细胞因子水平。采用Western blot法检测各组膝关节组织中HMGB1/RAGE/PI3K/Akt信号通路相关蛋白的表达情况。结果 与空白对照组比较,模型组膝关节直径增加、机械疼痛和热痛阈值降低,而相较于模型组,九味健步饮各剂量组和阳性药物组上述指标显著改善,且呈剂量依赖性(P<0.05)。此外,模型组Mankin评分和国际骨关节炎研究学会(Osteoarthritis Research Society International,OARSI)评分显著高于空白对照组,而九味健步饮干预则显著降低该评分,高剂量组效果最佳(P<0.05)。与空白对照组比较,模型组一氧化氮(nitric oxide,NO)和丙二醛(malondialdehyde,MDA)水平上升,超氧化物歧化酶(superoxide dismutase,SOD)和谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)水平下降,肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和白细胞介素-1β(interleukin-1β,IL-1β)水平同样显著升高。而与模型组比较,九味健步饮尤其是在高剂量下能显著抑制氧化应激与炎性反应(P<0.05)。同时,模型组中HMGB1、RAGE、p-PI3K/PI3K和p-Akt/Akt的表达较空白对照组增加,而九味健步饮干预呈剂量依赖性下调这些蛋白的表达(P<0.05)。结论九味健步饮通过抑制HMGB1/RAGE/PI3K/Akt信号通路进而减轻膝骨关节炎大鼠的氧化应激和炎性损伤,改善软骨病理变化,具有潜在治疗价值。 |
| 中文关键词:九味健步饮 膝骨关节炎 氧化应激 HMGB1 PI3K/Akt |
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| Effects of Jiuwei Jianbu Drink on Oxidative Stress and Inflammatory Injury in Rats with Knee Osteoarthritis via the HMGB1/RAGE/PI3K/Akt Signaling Pathway. |
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| Abstract:Objective To investigate the effects of Jiuwei Jianbu Drink on oxidative stress and inflammatory injury in rats with knee osteoarthritis via the high mobility group box-1 protein (HMGB1)/receptor for advanced glycation endproducts (RAGE)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Methods A total of 60 rats were randomly divided into six groups according to the random number table method:blank control group, model group, positive drug group, and Jiuwei Jianbu Drink low-, medium-, and high-dose groups, with 10 rats in each group. Except for the blank control group, knee osteoarthritis models were established in the other groups, which were then subjected to corresponding treatments. Knee joint diameter and mechanical pain and thermal pain threshold changes were observed. Hematoxylin-eosin staining and safranin O/fast green staining were used to assess pathological changes in cartilage tissue. Oxidative stress markers and inflammatory factor levels in knee joint cartilage tissue of each group were measured. Western blot was used to detect the expression of proteins related to the HMGB1/RAGE/PI3K/Akt signaling pathway in knee joint tissues. Results Compared with the blank control group, the model group exhibited increased knee joint diameter and decreased mechanical pain and thermal pain threshold. Jiuwei Jianbu Drink at all doses groups and the positive control group significantly improved these indicators in a dose-dependent manner (P<0.05). Additionally, the Mankin score and Osteoarthritis Research Society International (OARSI) score in the model group were significantly higher than those in the blank control group, while Jiuwei Jianbu Drink intervention significantly reduced the OARSI score, with the best effect observed in the high-dose group (P<0.05). Compared with the blank control group, the model group showed increased levels of nitric oxide (NO) and malondialdehyde (MDA), decreased levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and significantly elevated levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β). Compared with the model group, Jiuwei Jianbu Drink significantly inhibited oxidative stress and inflammatory responses, especially at high doses (P<0.05). Moreover, the expression of HMGB1, RAGE, p-PI3K/PI3K, and p-Akt/Akt in the model group was higher than that in the blank control group, while Jiuwei Jianbu Drink intervention dose-dependently downregulated the expression of these proteins (P<0.05). Conclusion Jiuwei Jianbu Drink alleviates oxidative stress and inflammatory injury in rats with knee osteoarthritis by inhibiting the HMGB1/RAGE/PI3K/Akt signaling pathway, thereby improving cartilage pathological changes and demonstrating potential therapeutic value. |
| keywords:Jiuwei Jianbu Drink Knee osteoarthritis Oxidative stress HMGB1 PI3K/Akt |
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