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| 基于NF-κB/Caspase-3凋亡信号通路探讨龟鹿固膝颗粒对KOA大鼠的作用机制 |
| Mechanism of action of Guilu Guxi Granules on KOA rats by NF-κB / Caspase-3 apoptosis signaling pathway |
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| DOI：10.3969/j.issn.1006-7108.2026.09.004 |
| 中文关键词: 龟鹿固膝颗粒 NF-κB/Bcl-xl信号通路 凋亡 膝骨关节炎 软骨 |
| 英文关键词:Guilu Guxi granules NF-κB p65/Bcl-xL pathway apoptotic knee osteoarthritis cartilage |
| 基金项目:甘肃省自然科学基金（22JR5RA640，23JRRA1679）；国家中医药管理局高水平中医药重点学科建设项目（zyyzdxk-2023203） |
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| 中文摘要: |
| 目的 探讨龟鹿固膝颗粒抑制膝骨关节炎（knee osteoarthritis，KOA）软骨退变的作用机制。方法选取2月龄SPF级雄性SD大鼠共36只，随机数字表法分为假手术组、模型组、依托考昔组（阳性对照组）和龟鹿固膝颗粒高、中、低组，各给药组给予相应药物灌胃，除假手术组行切开皮肤后直接缝合外，其余各组均采用改良Hulth法建立大鼠KOA模型。灌胃每日1次，连续干预14 d后，HE、Masson染色观察关节软骨组织形态结构和胶原纤维含量的变化；ELISA法检测大鼠血清中白细胞介素1β（interleukin-1β，IL-1β）、肿瘤坏死因子-α（tumour necrosis factor-α，TNF-α）；Western-blot检测软骨组织中NF-κB p65、Bcl-xL、IkBα、Caspase-3的表达量。结果 ①HE染色显示：假手术组软骨结构清晰，表面平整、光滑。模型组软骨细胞增生，结构紊乱，部分软骨表面与增生滑膜相连层次不清。龟鹿固膝颗粒组软骨细胞排列较为整齐，软骨厚度较假手术组增厚，未见结构紊乱软骨细胞，但不同剂量组间比较未见明显差异。②大鼠血清IL-1β、TNF-α的表达量，模型组显著高于假手术组（P＜0.01），龟鹿固膝颗粒组显著低于模型组（P＜0.01）。③关节软骨组织中NF-κB p65、Bcl-xL、Caspase-3蛋白表达量，模型组显著高于假手术组（P＜0.01），龟鹿固膝颗粒组显著低于模型组（P＜0.01）；IkBα表达量，模型组显著低于假手术组（P＜0.01），龟鹿固膝颗粒组显著高于模型组（P＜0.01）。结论 龟鹿固膝颗粒通过抑制炎症反应，降低血清中TNF-α、IL-1β含量，继而可能通过NF-κB p65/Bcl-xL/Caspase-3通路软骨细胞过度凋亡，延缓软骨退变。 |
| 英文摘要: |
| Objective To investigate the mechanism of Guilu Guxi Granules in inhibiting cartilage degeneration in knee osteoarthritis (KOA). Methods Thirty-six 2-month-old SPF-grade male SD rats were randomly divided into six groups: sham-operated group, model group, etoricoxib group (positive control), and high-dose, medium-dose, and low-dose Guilu Guxi Granules groups. Rats in all the treatment groups received corresponding drugs via gastric gavage. Except for the sham-operated group (skin incision followed by suturing), KOA models were established in the other groups using the modified Hulth method. After 14 days of daily intervention, changes in cartilage histomorphology and collagen fiber content were observed via HE or Masson staining. Serum levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were measured with ELISA. Western blotting was used to detect the expressions of NF-κB p65, IkBa, Bcl-xL, and Caspase-3 in the cartilage tissues. Results (1) HE staining revealed that rats in the sham-operated group exhibited clear cartilage structure with a smooth surface. Rats in the model group showed proliferated chondrocytes, disorganized structure, and unclear layers between the cartilage surface and hyperplastic synovium. Rats in the Guilu Guxi Granules groups displayed orderly chondrocyte alignment, thickened cartilage compared to the sham group, and no structural disorganization, with no significant differences among all the dose groups. (2) Serum IL-1β and TNF-α levels were significantly higher in the model group than those in the sham group (P<0.01, P<0.01) and were significantly lower than those in the Guilu Guxi Granules groups (P<0.01, P<0.01). (3) NF-κB p65, Bcl-xL, and Caspase-3 protein expressions in the cartilage tissues were significantly higher in the model group than in the sham group (P<0.01) and were lower than in the Guilu Guxi Granules groups (P<0.01). IkBa expression was significantly lower in the model group than that in the sham group (P<0.01) and was higher in the Guilu Guxi Granules groups than that in the model group (P<0.01). Conclusion Guilu Guxi Granules reduce the serum contents of TNF - α and IL-1 β by inhibiting the inflammatory response, and then may delay the cartilage degeneration by excessive apoptosis of chondrocytes through NF-κB p65 / Bcl-xL / Caspase-3 pathway. |
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