Page 62 - 《中国药房》2025年3期

高良姜素对膝关节炎大鼠软骨细胞自噬和凋亡的影响
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杨 青 ，黄 伟 ，刘清毅 ，周仲瑜（1.湖北省妇幼保健院康复理疗科，武汉 430070；2.湖北省中医院针灸科，
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武汉 430070；3.武汉市青山区冶金街社区卫生服务中心中医科，武汉 430070）
中图分类号 R965；R285.5 文献标志码 A 文章编号 1001-0408（2025）03-0312-06
DOI 10.6039/j.issn.1001-0408.2025.03.09

摘 要 目的 探讨高良姜素（GLA）调节腺苷一磷酸活化的蛋白质激酶（AMPK）/哺乳动物雷帕霉素靶蛋白（mTOR）/UNC-51样
激酶1（ULK1）信号通路对膝关节炎（KOA）大鼠软骨细胞自噬和凋亡的影响。方法 构建KOA大鼠模型，将其分为模型组，GLA
低、中、高剂量组（皮下注射 100、200、400 μg/kg 的 GLA），GLA+Compound C 组（皮下注射 400 μg/kg 的 GLA+0.2 mg/kg 的 AMPK
抑制剂Compound C），每组10只；另选取10只正常饲养的大鼠作为假手术组。末次给药后，检测大鼠膝关节肿胀程度，观察大鼠
膝关节软骨组织病理学；检测大鼠血清中基质金属蛋白酶13（MMP-13）、白细胞介素1β（IL-1β）水平；观察大鼠骨细胞自噬情况；
检测大鼠软骨细胞凋亡情况；检测大鼠膝关节软骨组织中AMPK/mTOR/ULK1信号通路相关蛋白磷酸化水平。结果 与假手术组
相比，模型组大鼠关节软骨细胞排列紊乱，细胞核固缩，关节软骨层纤维化严重，且伴有大量炎症细胞浸润；膝关节肿胀程度，软骨
细胞自噬空泡数、凋亡率，血清中MMP-13、IL-1β水平，膝关节软骨组织中mTOR蛋白的磷酸化水平均显著升高（P＜0.05）；膝关
节软骨组织中AMPK、ULK1蛋白的磷酸化水平均显著降低（P＜0.05）。与模型组相比，GLA低、中、高剂量组大鼠膝关节软骨损
伤明显改善，炎症细胞浸润减轻，上述定量指标除自噬空泡数进一步升高外均显著逆转，且具有剂量依赖性（P＜0.05）。与GLA
高剂量组比较，GLA+Compound C组大鼠膝关节软骨损伤和炎症细胞浸润加重，上述定量指标均显著逆转（P＜0.05）。结论 GLA
可促进KOA大鼠软骨细胞自噬，抑制细胞凋亡，其作用机制可能与激活AMPK/mTOR/ULK1信号通路有关。
关键词 高良姜素；膝关节炎；软骨细胞；自噬；凋亡；AMPK/mTOR/ULK1信号通路

Effects of galangin on autophagy and apoptosis of chondrocytes in knee osteoarthritis rats
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YANG Qing ，HUANG Wei ，LIU Qingyi ，ZHOU Zhongyu（1. Dept. of Rehabilitation and Physiotherapy， Hubei
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Maternal and Child Health Hospital， Wuhan 430070， China；2. Dept. of Acupuncture and Moxibustion， Hubei
Provincial Hospital of Traditional Chinese Medicine， Wuhan 430070， China；3. Dept. of Traditional Chinese
Medicine， Wuhan Qingshan District Metallurgical Street Community Health Service Center， Wuhan 430070，
China）

ABSTRACT OBJECTIVE To investigate the effects of galangin （GLA） on autophagy and apoptosis of chondrocytes in knee
osteoarthritis （KOA） rats by regulating the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of
rapamycin （mTOR）/UNC-51-like kinase 1 （ULK1） signaling pathway. METHODS KOA rat model was constructed and separated
into model group， L-GLA， M-GLA， H-GLA groups [subcutaneous injection of 100， 200， 400 μg/kg GLA]， GLA+Compound C
group [subcutaneous injection of 400 μg/kg GLA+0.2 mg/kg AMPK inhibitor Compound C]， with 10 rats in each group.
Additionally， 10 normally fed rats were selected as the sham operation group. After the last medication， the degree of knee joint
swelling of rats in each group was detected； the pathology of knee joints in KOA rats was observed. The serum expressions of
matrix metalloproteinase 13 （MMP-13） and interleukin-1β （IL-1β） in KOA rats were detected； the autophagy of chondrocytes in
KOA rats was observed； the chondrocyte apoptosis in KOA rats was detected； the phosphorylation of AMPK/mTOR/ULK1
pathway-related proteins in cartilage tissue of knee joint were detected in rats. RESULTS Compared with the sham operation
group， the arrangement of articular chondrocytes in the model group was disordered， with nuclear pyknosis and severe fibrosis of
the articular cartilage layer， accompanied by a large amount of inflammatory cell infiltration； the degree of joint swelling， the
number of autophagic vacuoles and apoptosis rate of chondrocytes， serum levels of MMP-13 and IL-1β， and the phosphorylation of
mTOR protein in cartilage tissue of knee joint were all increased significantly （P＜0.05）， while the phosphorylation of AMPK and
ULK1 protein were all decreased significantly in cartilage tissue of knee joint （P＜0.05）. Compared with the model group， L-
GLA， M-GLA， H-GLA groups showed significant
improvement in joint cartilage injury and reduced infiltration of
Δ 基金项目 湖北省科技计划项目（No.2022EHB054）
＊第一作者 副主任医师。研究方向：中医康复。E-mail：yq37rf@ inflammatory cells in rats. The above quantitative indicators
163.com were significantly reversed in a dose-dependent manner，

· 312 · China Pharmacy 2025 Vol. 36 No. 3 中国药房 2025年第36卷第3期