首页|水晶兰苷调节PUM1-TLR4/MyD88信号通路改善IL-1β诱导软骨细胞炎症反应的机制研究

水晶兰苷调节PUM1-TLR4/MyD88信号通路改善IL-1β诱导软骨细胞炎症反应的机制研究

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目的 研究水晶兰苷对大鼠膝软骨细胞中Pumilio RNA结合家族成员1(Pumilio RNA-binding family member 1，PUM1)-Toll 样受体 4(Toll like receptor 4，TLR4)/髓样分化因子 88(myeloid differentiation primary response 88，MyD88)信号通路及白细胞介素(interleukin，IL)-1β、IL-6 和肿瘤坏死因子(tumor necrosis factor，TNF)-a相关炎性因子的影响，探讨水晶兰苷对大鼠膝骨关节炎软骨细胞的作用机制。方法 将大鼠软骨细胞随机分为对照组、模型组、低剂量组、高剂量组，除对照组外，其余3组均通过10 ng/mL的IL-1β诱导细胞炎症，构建大鼠膝关节炎模型;低剂量组、高剂量组分别给予25 μg/mL、50 μg/mL水晶兰苷进行24 h干预。酶联免疫吸附剂测定法(enzyme linked immuno sorbent assay，ELISA)检测上清液中 IL-1β、IL-6 和 TNF-a 的含量，聚合酶链式反应(polymerase chain reaction，PCR)检测软骨细胞中PUM1、TLR4和MyD88的mRNA表达水平，蛋白免疫印迹法检测软骨细胞中PUM1、TLR4和MyD88的蛋白表达水平。结果 与对照组比较，模型组上清液中IL-1β、IL-6及TNF-α含量均升高(P＜0。05)，PUM1的mRNA及蛋白表达水平降低(P＜0。05)，TLR4和MyD88的mRNA及蛋白表达水平均升高(P＜0。05);与模型组比较，低剂量组和高剂量组的IL-1β、IL-6及TNF-α含量均降低(P＜0。05)，PUM1的mRNA及蛋白表达水平升高(P＜0。05)，TLR4和MyD88的mRNA及蛋白表达水平均降低(P＜0。05)。结论 水晶兰苷通过上调PUM1表达，抑制TLR4和MyD88信号通路的传递，进而降低下游炎性因子TNF-α、IL-1β及IL-6表达。
The Mechanism of Monotropein Regulating the PUM1-TLR4/MyD88 Signaling Pathway to Improve Interleukin-1p-Induced Inflammatory Response in Chondrocytes
Objective To study the effects of monotropein on Pumilio RNA-binding family member 1(PUM1)-Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)signaling pathway,and IL-1β,IL-6,and TNF-αrelated inflammatory factors in rat knee chondrocytes,and to explore the mechanism of monotropein on rat knee osteoarthritis chondrocytes.Methods Rat chondrocytes were randomly divided into a control group,a model group,a low-dose group,and a high-dose group.Except for the control group,the other three groups were induced with 10 ng/mL IL-1β to induce cell inflammation and construct a rat knee arthritis model.The low-dose group and the high-dose group were treated with 25 μg/mL and 50 μg/mL monotropein for 24 hours,respectively.The contents of IL-1β,IL-6,and TNF-α in the supernatant were detected by enzyme-linked immunosorbent assay(ELISA).The mRNA expression levels of PUM1,TLR4,and MyD88 in chondrocytes were detected by PCR.The protein expression levels of PUM1,TLR4,and MyD88 in chondrocytes were detected by Western blot.Results Compared with the control group,the contents of IL-1β,IL-6 and TNF-α in the supernatant of the model group were all increased(P＜0.05),while the mRNA and protein expression levels of PUM1 were decreased(P＜0.05),the mRNA and protein expression levels of TLR4 and MyD88 were both increased(P＜0.05).Compared with the model group,the contents of IL-1β,IL-6 and TNF-α in the low-dose group and high-dose group were all decreased(P＜0.05),while the mRNA and protein expression levels of PUM1 were increased(P＜0.05),the mRNA and protein expression levels of TLR4 and MyD88 were both decreased(P＜0.05).Conclusion Monotropein inhibits the transmission of TLR4 and MyD88 signal pathways by up-regulating the expression of PUM1,and then reduces the expression of downstream inflammatory factors TNF-α,IL-1β,and IL-6.

monotropeinPumilio rna-binding family member 1Toll-like receptor 4myeloid differentiation primary response 88inflammationchondrocytes

徐开民、赵红燕、邓鹏、丁晓明、咸宝安、柏明晓、杨彬

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山东省日照市中医医院髋膝骨科,山东 日照 276800

水晶兰苷 Pumilio RNA结合家族成员1 Toll样受体4 髓样分化因子88 炎症 软骨细胞

2024

实用骨科杂志
中华医学会山西分会,北京大学第三医院

实用骨科杂志

CSTPCD
影响因子：1.239
ISSN：1008-5572
年,卷(期)：2024.30(12)