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骨碎补总黄酮调控Notch1/Hes1信号轴促进软骨细胞自噬并抑制凋亡的机制研究
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| 篇名： | 骨碎补总黄酮调控Notch1/Hes1信号轴促进软骨细胞自噬并抑制凋亡的机制研究 |
| TITLE： | Regulation of Notch1/Hes1 signaling axis by total flavonoids of Drynariae Rhizoma for promoting chondrocyte autophagy and inhibiting apoptosis：a mechanistic study |
| 摘要： | 目的 探究骨碎补总黄酮（TFRD）调控Notch1/发状分裂相关增强子1（Hes1）信号轴对脂多糖（LPS）诱导的软骨细胞自噬及凋亡的影响。方法采用5μg/mLLPS处理人软骨细胞系C28/I2细胞构建体外炎症损伤模型，将细胞分为正常对照组、模型组、TFRD组（200μg/mL）、TFRD+过氧化物氧化还原酶1（Prdx1）小干扰RNA（si-Prdx1）组和TFRD+si-Prdx1阴性对照（si-NC）组，每组设6个复孔。细胞以si-Prdx1或si-NC转染24h、TFRD预处理2h，再以LPS处理，总计培养48h。检测细胞凋亡率、凋亡细胞占比、单丹磺酰尸胺（MDC）荧光强度和基质金属蛋白酶13（MMP-13）、含Ⅰ型血小板结合蛋白基序的解聚蛋白样金属蛋白酶5（ADAMTS5）、软骨寡聚基质蛋白（COMP）含量以及X连锁凋亡抑制蛋白（XIAP）、多腺苷二磷酸核糖聚合1（PARP1）、Beclin-1、微管相关蛋白1轻链3Ⅱ/Ⅰ（LC3-Ⅱ/Ⅰ）、PTEN诱导激酶1（PINK1）、Notch1、Hes1、Prdx1蛋白表达情况。结果与模型组比较，TFRD组细胞凋亡率、凋亡细胞占比和MMP-13、ADAMTS5含量以及PARP1蛋白表达水平均显著降低，MDC荧光强度、COMP含量和XIAP、Beclin-1、LC3-Ⅱ/Ⅰ、PINK1、Notch1、Hes1、Prdx1蛋白表达水平均升高（P＜0.05）。与TFRD+si-NC组比较，TFRD+si-Prdx1组细胞中除Notch1、Hes1以外上述指标的变化均被显著逆转（P＜0.05）。结论TFRD可能通过激活Notch1/Hes1信号轴上调下游靶分子Prdx1的表达，进而抑制LPS诱导的软骨细胞凋亡、促进其保护性自噬，从而改善软骨代谢稳态。 |
| ABSTRACT： | OBJECTIVE To investigate the effects of total flavonoids of Drynariae Rhizoma （TFRD） on autophagy and apoptosis in LPS-induced chondrocytes via the regulation of the Notch1/hairy and enhancer of split 1 （Notch1/Hes1） signaling axis. METHODS Human chondrocyte cell line C28/I2 cells were cultured with 5 μg/mL LPS to esta blish in vitro inflammatory injury model. The cells were separated into normal control group， model group， TFRD group （200 μg/mL）， TFRD+peroxiredoxin 1 （Prdx1） small interfering RNA （si-Prdx1） group and TFRD+si-Prdx1 negative control （si-NC） group， with 6 replicate wells in each group. Cells were transfected with si-Prdx1 or si-NC for 24 hours， pretreated with TFRD for 2 hours， and then exposed to LPS， with a total culture duration of 48 hours. Apoptotic rate， the proportion of apoptotic cells， monodansylcadaverine （MDC） fluorescence intensity， as well as the contents of matrix metalloproteinase-13 （MMP-13）， a disintegrin and metalloproteinase with thrombospondin motifs 5 （ADAMTS5）， and cartilage oligomeric matrix protein （COMP） were measured. Additionally， the protein expression levels of X-linked inhibitor of apoptosis protein （XIAP）， poly（ADP-ribose） polymerase 1 （PARP1）， Beclin-1， microtubule-associated protein 1 light chain 3 Ⅱ/Ⅰ （LC3-Ⅱ/Ⅰ）， PTEN-induced putative kinase 1 （PINK1）， Notch1， Hes1， and Prdx1 were assessed. RESULTS Compared with model group， the apoptotic rate， the proportion of apoptotic cells， the contents of MMP-13 and ADAMTS5 as well as protein expressions of PARP1 were significantly decreased， while MDC fluorescence intensity， COMP content， protein expressions of XIAP， Beclin-1， LC3-Ⅱ/Ⅰ， PINK1， Notch1， Hes1 and Prdx1 were significantly increased （ P ＜0.05）. Compared with TFRD+si-NC group， the changes in the aforementioned indicators （except for Notch1 and Hes1） in the cells of the TFRD+si-Prdx1 group were significantly reversed （ P ＜0.05）. CONCLUSIONS TFRD may activate the Notch1/Hes1 signaling axis， and up-regulate the expression of the downstream target molecule Prdx1， thereby inhibiting LPS-induced chondrocyte apoptosis， promoting protective autophagy， and consequently improving cartilage metabolic homeostasis. |
| 期刊： | 2026年第37卷第08期 |
| 作者： | 鲁林；方虹 |
| AUTHORS： | LU Lin，FANG Hong |
| 关键字： | 骨碎补总黄酮；软骨细胞；Notch受体1/Hes1信号轴；自噬；凋亡 |
| KEYWORDS： | total flavonoids of Drynariae Rhizoma； chondrocyte； Notch1/Hes1 signaling axis； autophagy； apoptosis |
| 阅读数： | 1 次 |
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