黄芪甲苷可减轻白细胞介素1β诱导软骨细胞的炎症反应  

Astragaloside Ⅳ can reduce interleukin-1beta-induced chondrocyte inflammation

作　　者：黄少烁 李嘉程 骆帝 朱凯 许波[2] 薛远亮 阎博昭 李刚 Huang Shaoshuo;Li Jiacheng;Luo Di;Zhu Kai;Xu Bo;Xue Yuanliang;Yan Bozhao;Li Gang(The First Clinical Medical College of Shandong University of Traditional Chinese Medicine,Jinan 250014,Shandong Province,China;The Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250014,Shandong Province,China)

机构地区：[1]山东中医药大学第一临床医学院,山东省济南市250014 [2]山东中医药大学附属医院,山东省济南市250014

出　　处：《中国组织工程研究》2023年第26期4113-4119,共7页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金(82074453),项目负责人:李刚;山东省医药卫生科技发展计划项目(202004071045),项目负责人:许波。

摘　　要：背景:骨性关节炎是一种最常见的退行性疾病,但目前仍无延缓或逆转病情的药物,只能消炎镇痛以短期内缓解症状、改善病情。黄芪甲苷是黄芪中一种具有调节免疫、缺血保护、心脏保护、抗炎、抗病毒和抗肿瘤等作用的活性成分。目的:探讨黄芪甲苷对白细胞介素1β诱导的小鼠骨关节软骨细胞ATDC5损伤的作用及相关机制。方法:将ATDC5细胞随机分为空白对照组、模型组、单体组、实验组。空白对照组细胞不加任何干预;模型组细胞用100μg/L白细胞介素1β处理;单体组细胞用5μg/L黄芪甲苷处理,实验组细胞用100μg/L白细胞介素1β和5μg/L黄芪甲苷处理。干预18 h后,采用CCK-8检测细胞增殖活性,Western blot和qRT-PCR检测基质金属蛋白酶3、基质金属蛋白酶9、基质金属蛋白酶13、Ⅱ型胶原、SDF-1、CXCR4的蛋白和mRNA表达变化,甲苯胺蓝染色检测细胞形态改变和细胞数量,锥虫蓝染色检测细胞存活率。结果与结论:①与空白对照组比较,白细胞介素1β(100μg/L)明显抑制ATDC5细胞的增殖活性,相关炎症标志物基质金属蛋白酶3、基质金属蛋白酶9、基质金属蛋白酶13的表达升高,Ⅱ型胶原的表达降低,SDF-1、CXCR4的表达升高,SDF-1/CXCR4信号通路激活,诱导细胞出现炎症反应;②与模型组比较,实验组基质金属蛋白酶3、基质金属蛋白酶9、基质金属蛋白酶13的表达降低,Ⅱ型胶原的表达升高,证实黄芪甲苷可以减轻白细胞介素1β诱导的软骨细胞损伤;③此外,与模型组比较,实验组CXCR4、SDF-1的表达降低,证实了黄芪甲苷是通过SDF-1/CXCR4信号通路减轻白细胞介素1β诱导的软骨细胞炎症反应。BACKGROUND:Osteoarthritis is one of the most common degenerative diseases,and there are still no drugs to delay or reverse the disease.Only antiinflammatory and analgetic treatments can be performed to relieve symptoms and improve patient’s conditions in the short term.Astragaloside Ⅳ is an active component of Astragalus membranaceus with immunomodulatory,ischemic protection,cardiac protection,anti-inflammatory,antiviral,and anti-tumor effects.OBJECTIVE:To investigate the effects of astragaloside IV on interleukin-1β-induced ATDC5 cell injury and its related mechanism.METHODS:ATDC5 cells we re randomly divided into blank control group,model group,monomer group,and expe rimental group.There was no intervention in the blank control group.Cells in the latter three groups were treated with 100 μg/L interleukin-1β,5μg/L astragaloside Ⅳ,and 100 μg/L interleukin-1β+5 μg/L astragaloside Ⅳ,respectively.After 18 hours of treatment,cell counting kit-8 was used to detect cell proliferation.Western blot and qRT-PCR were used to detect the expression of matrix metalloproteinases 3,9,13,type Ⅱ collagen,stromal cell-derived factor 1(SDF-1),and C-X-C chemokine receptor 4(CXCR4) at protein and mRNA levels,respectively.Toluidine blue staining was used to detect cell morphological changes and cell numbers,and trypan blue staining was used to detect cell viability.RESU LTS AND CONCLUSION:Interleukin-1β(100 μg/L) significantly inhibited the activity of AT DC5 cells,increased the expression of inflammato ry markers(matrix metalloproteinases 3,9,and 13),decreased the expression of type Ⅱ collagen,increased the expression of SDF-1 and CXCR4,activated the SDF-1/CXCR4 pathway,and induced inflammatory responses in cells.Compared with the model group,astragaloside Ⅳ significantly reduced the expression of matrix metalloproteinases 3,9,and 13,and increased the expression of type Ⅱ collagen,indicating that astragaloside Ⅳ can alleviate chondrocyte injury induced by interleukin-1β.In addition,the expression of CXCR4

关 键 词：骨性关节炎 黄芪甲苷 SDF-1/CXCR4信号通路 ATDC5细胞 炎症反应 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学] R274.9