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| 阿仑膦酸钠联合脂多糖引发巨噬细胞炎症反应的机制研究<sub><sup> </sup></sub> |
| Mechanism of Alendronate sodium combined with LPS induced inflammatory responses in macrophages* |
| 投稿时间：2019-10-28 修订日期：2019-10-28 |
| DOI： |
| 中文关键词: 阿仑膦酸钠 脂多糖 半胱氨酸天冬氨酸蛋白酶1 白介素1β 双膦酸盐类相关性颌骨 |
| 英文关键词: Alendronate sodium LPS Caspase1 IL-1β BRONJ |
| 基金项目:国家自然科学基金项目（面上项目，重点项目，重大项目） |
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| 中文摘要: |
| 目的：阐明阿仑膦酸钠以及阿仑膦酸钠联合脂多糖引发巨噬细胞炎症反应的分子机制,进一步探究双膦酸盐类药物相关性颌骨坏死发生的相关机制。方法：选取小鼠单核巨噬细胞白血病细胞Raw264.7和小鼠骨髓来源的巨噬细胞BMDM作为细胞模型,分为对照组、脂多糖组、阿仑膦酸钠组以及阿仑膦酸钠联合脂多糖组,分别检测Caspase1,IL-1β及IL-18的表达水平,用Western blot检测Raw264.7细胞中Caspase1的蛋白水平变化,用流式观察BMDM细胞中Caspase1荧光强度变化。结果：除了BMDM细胞中阿仑膦酸钠联合脂多糖组IL-1β的表达水平相比阿仑膦酸钠组没有增加外(P>0.05),Raw264.7和BMDM细胞中阿仑膦酸钠联合脂多糖组Caspase1,IL-1β及IL-18的mRNA表达水平均高于对照组(P<0.05)和阿仑膦酸钠组(P<0.05)。Raw264.7细胞中阿仑膦酸钠联合脂多糖组cleaved Caspase 1蛋白表达水平最高。BMDM细胞中阿仑膦酸钠联合脂多糖组Caspase 1荧光强度最高。然而加入组蛋白去甲基化酶抑制剂GSK-J4后,在Raw264.7和BMDM细胞中,阿仑膦酸钠联合脂多糖组Caspase1,IL-1β及IL-18的mRNA表达水平均有下降(P<0.05)。结论：阿仑膦酸钠联合脂多糖可以加剧阿仑膦酸钠的炎症反应,促进Caspase1,IL-1β及IL-18的表达,并在一定程度受到表观遗传的调控,提示感染及炎症因素可能对双膦酸盐类药物相关性颌骨坏死(BRONJ)的发生发展具有促进作用,同时提示我们可以在表观遗传方向寻找治疗BRONJ的新靶点。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the molecular mechanism of alendronate sodium combined with LPS induced inflammatory responses in macrophages and to further elaborate the mechanismof bisphosphonate related osteonecrosis of the jaws (BRONJ). Methods: Select Raw264.7 and bone marrow-derived macrophage (BMDM) as the cell models, which were divided into control group, LPS group, alendronate sodium group and alendronate sodium combined with LPS group respectively. Then we investigated the expressions of Caspase1, IL-1β and IL-18 in mRNA level. Caspase1 changes were detected with Western blot in Raw264.7, and Caspase1 fluorescence intensity changes were observed through flow cytometry in the BMDM. Results: The expressions of Caspase1, IL-1β and IL-18 in alendronate sodium combined with LPS group were higher than those in control group(P<0.05) and alendronate sodium group (P<0.05) in mRNA levels except IL-1β in BMDM cells.The expression of cleaved Caspase 1 in alendronate sodium combined with LPS group was highest in protein level in Raw264.7. Caspase1 fluorescence intensity in alendronate sodium combined with LPS group was highest in BMDM cells.In alendronate sodium combined with LPS group, however the transcription levels of Caspase1, IL-1β and IL-18 were decreased when exposed to histone demethylase inhibitor GSK-J4(P<0.05). Conclusions: Alendronate sodium combined with LPS can aggravate the inflammatory response of alendronate sodium and promote the expressions of Caspase1, IL-1β and IL-18,which can be regulated by epigenetic alterations. These data suggested that infection and inflammatory factors may play a role in promoting the development of BRONJ and there may be a therapeutic target in epigenetics for BRONJ. |
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