[1]罗锟,王智,鲁林.蓝萼甲素对膝骨关节炎大鼠软骨细胞自噬和凋亡的影响[J].中国中医骨伤科杂志,2025,33(05):6-12.[doi:10.20085/j.cnki.issn1005-0205.250502]
　LUO Kun,WANG Zhi,LU Lin.Effects of Glaucocalyxin A on Chondrocytes Autophagy and Apoptosis in Rat with Knee Osteoarthritis[J].Chinese Journal of Traditional Medical Traumatology & Orthopedics,2025,33(05):6-12.[doi:10.20085/j.cnki.issn1005-0205.250502]
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蓝萼甲素对膝骨关节炎大鼠软骨细胞自噬和凋亡的影响()
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《中国中医骨伤科杂志》[ISSN:1005-0205/CN:42-1340/R]

卷:
第33卷
期数:
2025年05期
页码:
6-12
栏目:
实验研究
出版日期:
2025-05-05

文章信息/Info

Title:
Effects of Glaucocalyxin A on Chondrocytes Autophagy and Apoptosis in Rat with Knee Osteoarthritis
文章编号:
1005-0205(2025)05-0006-07
作者:
罗锟1; 王智1; 鲁林1
1武汉市中医医院(武汉,430050)
Author(s):
LUO Kun1; WANG Zhi1; LU Lin1
1Wuhan Hospital of Traditional Chinese Medicine,Wuhan 430050,China.
关键词:
蓝萼甲素;  低氧诱导因子1α/腺病毒E1B相互作用蛋白3信号通路;  膝骨关节炎;  自噬;  凋亡
Keywords:
glaucocalyxin A;  hypoxia induction factor-1α/adenovirus E1B interacting protein 3 signaling pathway(HIF-1α/BNIP3);  knee osteoarthritis;  autophagy;  apoptosis
分类号:
R-33
DOI:
10.20085/j.cnki.issn1005-0205.250502
文献标志码:
A
摘要:
目的:探讨蓝萼甲素(GLA)对膝骨关节炎(KOA)大鼠软骨细胞自噬和凋亡及低氧诱导因子1α/腺病毒E1B相互作用蛋白3(HIF-1α/BNIP3)信号通路的影响。方法:构建膝骨关节炎大鼠模型,将造模成功大鼠随机分为KOA组、GLA低/高剂量组(GLA-L/GLA-H组)、GLA高剂量+si-NC组(GLA-H+si-NC组)、GLA高剂量+si-HIF-1α组(GLA-H+si-HIF-1α组),另取健康大鼠作为对照组(Control组); 对各组大鼠膝关节临床症状评分; ELISA法检测血清炎性因子水平; HE染色观察膝骨关节退变情况; TUNEL染色检测细胞凋亡; 免疫组化检测细胞自噬相关蛋白表达; Western Blot法检测HIF-1α/BNIP3信号通路相关蛋白表达。结果:KOA组较Control组结构破坏、退变现象明显,软骨浅层出现缺失及裂缝,且裂隙深达钙化层,潮线断裂,细胞数量减少、排列紊乱,炎性浸润明显,膝关节临床症状评分、IL-6、IL-1β、TNF-α水平及细胞凋亡率、Bax、C-caspase-3、beclin 1、BNIP3表达升高,P62、HIF-1α表达降低(P<0.05); GLA-L组及GLA-H组较KOA组结构破坏、退变现象得到改善,软骨表面相对平整光滑,潮线清晰,偶见微小裂隙,软骨细胞形态相对正常、排列相对整齐,少量细胞肿胀及炎性细胞浸润,膝关节临床症状评分、IL-6、IL-1β、TNF-α水平及细胞凋亡率、Bax、C-caspase-3、beclin 1、BNIP3表达降低,P62、HIF-1α表达升高(P<0.05); GLA-H+si-HIF-1α组较GLA-H+si-NC组结构破坏严重,软骨浅层缺失及裂缝加剧,潮线断裂,细胞排列紊乱且数量减少,炎性细胞浸润现象加剧,膝关节临床症状评分、IL-6、IL-1β、TNF-α水平及细胞凋亡率、Bax、C-caspase-3、beclin 1、BNIP3表达升高,P62、HIF-1α表达降低(P<0.05)。结论:蓝萼甲素可抑制膝骨关节炎大鼠软骨细胞自噬与凋亡,其作用机制与激活HIF-1α/BNIP3信号通路相关。
Abstract:
Objective:To investigate the effects of glaucocalyxin A(GLA)on chondrocytes autophagy,apoptosis and hypoxia induction factor 1α/adenovirus E1B interacting protein 3(HIF-1α/BNIP3)signaling pathway in knee osteoarthritis(KOA)rat.Methods:The KOA rat model was constructed,and the rats were randomly separated into KOA group,GLA low and high-dose groups(GLA-L,GLA-H groups),GLA high-dose+si-NC(GLA-H+si-NC group),and GLA high-dose+si-HIF-1α(GLA-H+si-HIF-1α group).The healthy rats were taken as control group.The clinical symptoms of knee joints in rats were scored; ELISA was applied to detect the serum levels of inflammatory factors; HE staining was applied to observe the degeneration of knee joints; TUNEL staining was applied to detect apoptosis; immunohistochemistry was applied to detect the protein expression of autophagy; Western Blot analysis of HIF-1α/BNIP3 signaling pathway related protein expression.Results:Compared with control group,KOA group showed obvious structural damage and degeneration,the shallow layer of cartilage was deficient and cracked,and the cracks reached the calcification layer,the tide line was broken,the number of cells was reduced,the arrangement was disordered,the inflammatory infiltration was obvious,the knee clinical symptom score,levels of IL-6,IL-1β,TNF-α,apoptosis rate,the expression of Bax,C-caspase-3,beclin 1,and BNIP3 elevated,the expression of P62 and HIF-1α reduced(P<0.05).Compared with KOA group,the structural destruction phenomenon of GLA-L and GLA-H groups showed improved structural damage and degeneration.The cartilage surface was relatively smooth,the tide line was clear,and occasionally small cracks were seen.The shape of chondrocytes was relatively normal and the arrangement was relatively neat,and a small amount of cells were swollen and inflammatory cell infiltrated,the knee clinical symptom score,levels of IL-6,IL-1β,TNF-α,apoptosis rate,the expression of Bax,C-caspase-3,beclin 1,and BNIP3 reduced,the expression of P62 and HIF-1α increased(P<0.05).Compared with the GLA-H+si-NC group,the GLA-H+si-HIF-1α group had severe structural destruction,aggravated loss and cracks of superficial cartilage,tidal line fracture,disordered cell arrangement and reduced number,intensified inflammatory cell infiltration phenomenon,the knee clinical symptom score,levels of IL-6,IL-1β,TNF-α,apoptosis rate,the expression of Bax,C-caspase-3,beclin 1,and BNIP3 increased,the expression of P62 and HIF-1α reduced(P<0.05).Conclusion:GLA can inhibit autophagy and apoptosis in KOA rats,and its mechanism is related to the activation of HIF-1α/BNIP3 signaling pathway.

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备注/Memo

备注/Memo:
基金项目:武汉市中医药科研项目(WZ24B06)
更新日期/Last Update: 2025-05-15