Targeted delivery of Nitric Oxide triggered by α-Glucosidase to Ameliorate NSAIDs-induced Enteropathy.
Targeted delivery of Nitric Oxide triggered by α-Glucosidase to Ameliorate NSAIDs-induced Enteropathy.
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DOI：
10.1016/j.redox.2022.102590
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发表时间：
2023-02
期刊：
影响因子：
11.4
通讯作者：
Hou, Jingli
中科院分区：
文献类型：
--
作者：
Wang, Xianglu;Shi, Jiarui;Xu, Zhixin;Wang, Dan;Song, Yuguang;Han, Guifang;Wang, Bangmao;Cao, Hailong;Liu, Yangping;Hou, Jingli
关键词：
非甾体抗炎药（NSAID）增加了严重小肠损伤的风险。开发有效的治疗策略来克服这个问题仍然具有挑战性。一氧化氮（NO）作为一种气体介质在小肠损伤中起保护作用。然而，用于NO的小的精氨酸特异性递送系统尚未报道。本研究通过将α-葡萄糖苷酶活化的NO供体共价接枝到壳聚糖上，合成了一种靶向于精氨酸的小分子NO供体（CS-NO）。体内外实验表明，CS-NO可被小肠α-葡萄糖苷酶激活，在小肠内释放NO。CS-NO预处理小鼠显著减轻吲哚美辛诱导的小肠损伤，如通过下调促炎细胞因子和趋化因子CXCL 1/KC的水平所证明的。此外，CS-NO还减弱吲哚美辛诱导的肠屏障功能障碍，如通过上调紧密连接蛋白水平和恢复杯状细胞和MUC 2产生水平所证明的。同时，CS-NO能有效地恢复小肠潘氏细胞对病原菌的防御功能。我们目前的研究为开发基于NO的非甾体抗炎药诱导的小肠损伤的治疗策略铺平了道路。将一种新型的NO供体（α-葡萄糖苷酶触发的NO供体）连接到壳聚糖上，制备了一种特异性的小分子NO供体（CS-NO），用于保护非甾体抗炎药（NSAID）引起的小肠损伤和炎症。首次开发了一种由α-葡萄糖苷酶触发释放NO的NO供体。首次将α-葡萄糖苷酶引发的NO释放供体连接到壳聚糖上，制备了高分子NO供体（CS-NO）。通过体内荧光成像和电子顺磁共振（EPR）研究了CS-NO的NO释放。NO释放材料（CS-NO）可明显减轻消炎痛引起的小肠损伤。
Nonsteroidal anti-inflammatory drugs (NSAIDs) increase risks of severe small intestinal injuries. Development of effective therapeutic strategies to overcome this issue remains challenging. Nitric oxide (NO) as a gaseous mediator plays a protective role in small intestinal injuries. However, small intestine-specific delivery systems for NO have not been reported yet. In this study, we reported a small intestine-targeted polymeric NO donor (CS–NO) which was synthesized by covalent grafting of α-glucosidase-activated NO donor onto chitosan. In vitro and in vivo experiments demonstrated that CS-NO could be activated by intestinal α-glucosidase to release NO in the small intestine. Pre-treatment of mice with CS-NO significantly alleviated small intestinal damage induced by indomethacin, as demonstrated by down-regulation of the levels of pro-inflammatory cytokines and chemokines CXCL1/KC. Moreover, CS-NO also attenuated indomethacin-induced gut barrier dysfunction as evidenced by up-regulation of the levels of tight junction proteins and restoration of the levels of goblet cells and MUC2 production. Meanwhile, CS-NO effectively restored the defense function of Paneth cells against pathogens in small intestine. Our present study paves the way to develop NO-based therapeutic strategy for NSAIDs-induced small intestinal injuries. A small intestine-specific polymeric NO donor (CS–NO) was developed by attaching a novel type of NO donor (α-glucosidase triggered NO donor) to chitosan for protection against NSAIDs-induced small intestinal injuries and inflammation. A type of nitric oxide (NO) donor triggered by α-glucosidase to release NO was firstly developed. Polymeric NO donor (CS–NO) has been firstly developed by attaching α-glucosidase triggered NO-releasing donor to chitosan. NO release from CS-NO was studied by in vivo fluorescent imaging and electron paramagnetic resonance (EPR). NO delivery material (CS–NO) significantly alleviated indomethacin-induced small intestinal damage.
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影响因子：
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作者：
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通讯作者：
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DOI：
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