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| 藁本内酯衍生物对软骨细胞外基质合成与分解代谢影响 |
| Effects of ligusticum cycloprolactam on synthesis and catabolism of extracellular matrix in chondrocytes |
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| DOI：10.3969/j.issn.1006-7108.2023.11.010 |
| 中文关键词: 骨关节炎 藁本内酯衍生物 软骨细胞外基质 白细胞介素-1β |
| 英文关键词:osteoarthritis ligusticum cycloprolactam Cartilage extracellular matrix Interleukin-1β |
| 基金项目:甘肃省青年科技基金计划(20JR10RA345)；兰州市城关区科技计划项目(2020-2-2-7)；甘肃中医药大学附属医院院内创新基金(gzfy-2019-12)；甘肃省科技计划资助（20JR5RA129）；兰州市科技发展指导性计划项目(2020-ZD-65)，甘肃省拔尖领军人才项目 |
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| 中文摘要: |
| 目的 探究藁本内酯衍生物(LIGc)对IL-1β诱导大鼠软骨细胞外基质合成与分解代谢的影响。方法 将大鼠软骨细胞分为空白对照组、IL-1β组及LIGc高剂量组（0.4 μmol/mL）、中剂量组（0.2 μmol/mL）、低剂量组（0.1 μmol/mL）组。CCK-8法检测细胞活力；细胞免疫荧光检测COL2α1和ACAN的表达；采用RT-qPCR检测软骨细胞中SOX9、PRG4、MMP-13、ADAMTS-5的基因表达水平。Western blot检测软骨细胞中HMGB1、COX2、TLR4、NF-κB p65的蛋白表达水平。结果 与正常组比较，IL-1β组软骨细胞增殖降低；COL2α1和ACAN的表达降低；SOX9、PRG4 mRNA表达下调，同时MMP-13、ADAMTS-5 mRNA表达上调；HMGB1、COX2、TLR4、NF-κB p65蛋白表达升高。与IL-1β组比较，LIGc能够促进软骨细胞的增殖；增强COL2α1和ACAN的表达；上调SOX9、PRG4 mRNA表达，同时下调MMP-13、ADAMTS-5 mRNA表达；下调HMGB1、COX2、TLR4、NF-κB p65蛋白表达。结论 LIGc能够抑制IL-1β所致炎症因子表达，上调软骨细胞外基质合成代谢因子、下调分解代谢因子延缓软骨细胞外基质降解的作用，其机制可能与OA免疫炎症反应的TLR4/NF-κB信号通路相关。 |
| 英文摘要: |
| Objective To investigate the effect of ligusticum cycloprolactam (LIGc) on IL-1β-induced extracellular matrix synthesis and catabolism in rat cartilage. Methods Rat chondrocytes were divided into blank control group, IL-1β group and LIGc high-dose (0.4 μmol/mL), medium-dose (0.2 μmol/mL) and low-dose (0.1 μmol/mL) groups; cell viability was detected by CCK-8 assay; cell immunofluorescence was performed to detect the expression of COL2α1 and ACAN; and chondrocyte gene expression levels were detected by RT-qPCR. gene expression levels of SOX9, PRG4, MMP-13 and ADAMTS-5 in the cells.The protein expression levels of HMGB1, COX2, TLR4, and NF-κB p65 in chondrocytes were detected by Western blot. Results Compared with the normal group, chondrocyte proliferation was reduced in the IL-1β group; the expression of COL2α1 and ACAN was decreased; the mRNA expression of SOX9 and PRG4 was downregulated, whereas the mRNA expression of MMP-13 and ADAMTS-5 was upregulated; and the protein expression of HMGB1, COX2, TLR4 and NF-κB p65 was increased. Compared with the IL-1β group, LIGc was able to promote the proliferation of chondrocytes; increase the expression of COL2α1 and ACAN.The expression of SOX9 and PRG4 mRNA was upregulated, while the expression of MMP-13 and ADAMTS-5 mRNA was downregulated. The protein expression of HMGB1, COX2, TLR4 and NF-κB p65 was downregulated. ConclusionLIGc can inhibit the expression of inflammatory factors induced by IL-1β, upregulate the anabolic factor of chondrocyte extracellular matrix and down-regulate the catabolic factor to delay the degradation of chondrocyte extracellular matrix. The mechanism may be related to the TLR4/NF-κB signalling pathway of the immune inflammatory response in osteoarthritis. |
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