中国骨质疏松杂志

麻黄碱调控AMPK/NF-κB信号通路改善大鼠膝骨关节炎的实验研究

Experimental study on ephedrine ameliorates knee osteoarthritis in rats by regulating AMPK/NF-κB signaling pathway

DOI：10.3969/j.issn.1006-7108.2023.10.003

英文关键词:ephedrine knee osteoarthritis AMPK/NF-κB signal pathway

基金项目:河南省中医药科学研究专项课题（2023ZY2097）；2021年河南省中医药拔尖人才培养项目资助[豫卫中医函（2021）15号]

作者	单位
王俊杰1 郭中华1* 史栋梁1 丁琳琳2	1. 河南省中医院骨病一科,河南郑州 450053 2. 金水区总医院中医科,河南郑州 450008

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中文摘要:

目的探讨麻黄碱（Ephedrine）调控腺苷酸活化蛋白激酶（AMPK）/核转录因子-κB（NF-κB）信号通路对大鼠膝骨关节炎（KOA）的影响。方法建立KOA大鼠模型，将大鼠分为Sham组、KOA组、Ephedrine组（40.0 mg/kg）、Ephedrine（40.0 mg/kg）+Compound C组（0.2 mg/kg），药物分组干预后，分别检测大鼠膝关节宽度与疼痛阈值，番红O-固绿染色观察软骨组织病理变化并进行Mankin评分，ELISA法检测关节液TNF-α、IL-1β、COX-2水平，免疫组化检测软骨组织IL-1β、MMP-13蛋白表达，Western blot检测AMPK/NF-κB通路相关蛋白水平。结果与Sham组比较，KOA组软骨组织损伤严重，膝关节宽度、Mankin评分、关节液TNF-α、IL-1β、COX-2水平及软骨组织IL-1β、MMP-13、p-NF-κB p65/NF-κB p65水平显著升高，疼痛阈值及软骨组织p-AMPK/AMPK水平显著降低（P＜0.05）；与KOA组比较，Ephedrine组软骨组织病理损伤减轻，膝关节宽度、Mankin评分、关节液TNF-α、IL-1β、COX-2水平及软骨组织IL-1β、MMP-13、p-NF-κB p65/NF-κB p65水平显著降低，疼痛阈值及软骨组织p-AMPK/AMPK水平显著升高（P＜0.05）；与Ephedrine组比较，Ephedrine+ Compound C组大鼠软骨组织损伤加重，膝关节宽度、Mankin评分、关节液TNF-α、IL-1β、COX-2水平及软骨组织IL-1β、MMP-13、p-NF-κB p65/NF-κB p65水平显著升高，疼痛阈值及软骨组织p-AMPK/AMPK水平显著降低（P＜0.05）。结论麻黄碱通过激活AMPK通路抑制NF-κB信号通路，抑制炎症反应，改善KOA大鼠软骨损伤。

英文摘要:

Objective To investigate the impact of ephedrine on knee osteoarthritis (KOA) in rats by regulating AMPK/NF-κB signaling pathway. Methods KOA rat models were established and grouped into Sham group, KOA group, Ephedrine group (40.0mg/kg), and Ephedrine group (40.0mg/kg)+Compound C group (0.2mg/kg). After drug grouping intervention, the knee joint width and pain threshold of rats were measured respectively,the pathological changes of cartilage tissue were observed with safranine O-solid green staining and Mankin score was performed,the levels of TNF-α, IL-1β and COX-2 in synovial fluid were detected by ELISA,the expression of IL-1β and MMP-13 proteins in cartilage tissue was detected by immunohistochemistry,Western blot was applied to detect the level of AMPK/NF-κB pathway related proteins. Results Compared with Sham group, the cartilage tissue of KOA group was seriously damaged,the knee joint width, Mankin score, levels of TNF-α, IL-1β, COX-2 in joint fluid, and levels of IL-1β, MMP-13, and p-NF-κB p65/NF-κB p65 in cartilage tissue were significantly higher, and the pain threshold and the level of p-AMPK/AMPK in cartilage tissue were significantly lower (P<0.05);compared with KOA group, the pathological damage of cartilage tissue in Ephedrine group was reduced,the knee joint width, Mankin score, levels of TNF-α, IL-1β, COX-2 in joint fluid, and levels of IL-1β, MMP-13, and p-NF-κB p65/NF-κB p65 in cartilage tissue were significantly lower, and the pain threshold and the level of p-AMPK/AMPK in cartilage tissue were significantly higher (P<0.05); compared with the Ephedrine group, the injury of cartilage tissue in the Ephedrine+Compound C group was aggravated,the knee joint width, Mankin score, levels of TNF-α, IL-1β, COX-2 in joint fluid, and levels of IL-1β, MMP-13, and p-NF-κB p65/NF-κB p65 in cartilage tissue were significantly higher, and the pain threshold and the level of p-AMPK/AMPK in cartilage tissue were significantly lower (P<0.05). Conclusion Ephedrine can inhibit NF-κB signal pathway, inhibit inflammatory reaction and improve cartilage injury in KOA rats by activating AMPK pathway.

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