TXNIP介导的NLRP3炎症小体激活在心肌微血管内皮细胞缺氧/复氧损伤中的作用 |
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引用本文: | 许倡涛,刘 毅,朱 迪,辛 超,杜志超,穆 楠,陶 凌. TXNIP介导的NLRP3炎症小体激活在心肌微血管内皮细胞缺氧/复氧损伤中的作用[J]. 心脏杂志, 2015, 27(5): 510-513 |
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作者姓名: | 许倡涛 刘 毅 朱 迪 辛 超 杜志超 穆 楠 陶 凌 |
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作者单位: | (第四军医大学:1.西京医院心血管内科,2.药学院药物基因组学教研室,3.药学院生物制药学教研室,陕西 西安 710032) |
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基金项目: | 国家自然科学基金项目资助(81170186)
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摘 要: | 目的 研究硫氧还蛋白结合蛋白(TXNIP)介导的NLRP3炎症小体激活在心肌微血管内皮细胞(CMECs)缺氧/复氧(H/R)损伤中的作用。方法 分离培养C57BL/6J小鼠CMECs,随机分为对照组、H/R损伤组、H/R+Scrambled siRNA组和H/R+TXNIP siRNA组。各组处理后使用ELISA试剂盒检测细胞IL-1β水平,采用免疫共沉淀的方法检测TXNIP和NLRP3的相互作用,Western blot检测TXNIP和NLRP3的表达水平,乳酸脱氢酶试剂盒检测细胞培养上清LDH释放情况和细胞Caspase-3活性。结果 与对照组相比,H/R后CMECs的NLRP3表达水平明显升高(P<0.05),NLRP3炎症小体激活(IL-1β水平升高,P<0.01),且TXNIP和NLRP3的结合效果明显增强(P<0.01)。运用TXNIP siRNA抑制TXNIP表达后行H/R处理,与H/R+Scrambled siRNA组相比,NLRP3炎症小体激活水平明显下降(IL-1β水平降低),细胞Caspase-3活力和LDH释放水平均显著降低(均P<0.05)。结论 在CMECs发生H/R损伤时,NLRP3炎症小体激活,TXNIP和NLRP3的相互作用增强;抑制TXNIP表达后,NLRP3炎症小体激活水平降低,内皮损伤减轻。说明TXNIP介导的NLRP3炎症小体激活参与CMECs的H/R损伤,可能成为CMECs的H/R损伤的新机制。
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关 键 词: | NLRP3 TXNIP 心肌微血管内皮细胞 缺氧/复氧损伤 |
收稿时间: | 2015-01-07 |
Effect of TXNIP mediated NLRP3 inflammasome activation on cardiac microvascular endothelial cells during hypoxia/reoxygenation injury |
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Abstract: | AIM To determine the effect of thioredoxin-interacting protein (TXNIP) mediated NLRP3 inflammasome activation on cardiac microvascular endothelial cells (CMECs) during hypoxia/reoxygenation (H/R) injury. METHODS CMECs isolated from the hearts of adult mice were randomized into control group, H/R group, H/R+scrambled siRNA group and H/R+TXNIP siRNA group. Levels of IL-1β were detected by ELISA kits. The interaction between TXNIP and NLRP3 was determined by immunoprecipitation. Expressions of TXNIP and NLRP3 were analyzed by Western blot, and caspase-3 activity and LDH release were assessed with test kits. RESULTS H/R increased NLRP3 expression (P<0.05), IL-1β level (P<0.01) and the interaction between TXNIP and NLRP3 (P<0.01) in CMECs compared with control group. Blocking TXNIP signaling with siRNA significantly inhibited NLRP3 activation (P<0.05) and alleviated endothelial injury evidenced by increased caspase-3 activity LDH release (P<0.05). CONCLUSION H/R injury promotes NLRP3 activation and increases the interaction between TXNIP and NLRP3. Blocking TXNIP signaling reduces NLRP3 activation and endothelial injury. TXNIP mediated NLRP3 activation may be a novel mechanism in H/R injury of CMECs. |
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