Dl-3-n-butylphthalide pretreatment attenuates renal ischemia/reperfusion injury
Dl-3-n-butylphthalide pretreatment attenuates renal ischemia/reperfusion injury
复制标题
Dl-3-正丁基苯酞预处理减轻肾缺血/再灌注损伤
DOI：
10.1016/j.bbrc.2021.04.006
复制
发表时间：
2021-04-14
影响因子：
3.1
通讯作者：
Wang, Niansong
中科院分区：
文献类型：
--
作者：
Dong, Yang;Yin, Jianyong;Wang, Niansong
背景：肾缺血再灌注损伤（IRI）是临床上日益关注的问题，其发病率和死亡率都很高。目前没有有效的预防方案可用于预防其发生并改善其临床预后。DL-3-正丁基苯酞（NBP）在中国已用于脑卒中治疗多年。关于它在预防肾损伤中的作用知之甚少。方法：雄性C57 BL/6 J小鼠肾脏缺血33 min，再灌注24 h。在手术前通过灌胃给予NBP。以血肌酐、肾损伤指标及肾脏病理变化评价NBP的肾脏保护作用。此外，还检测了肾组织中的炎症、氧化应激和凋亡标志物。在体外，用NBP诱导HK 2细胞，然后暴露于缺氧/复氧（H/R）。通过检测细胞活力和凋亡相关蛋白的含量来验证NBP的保护作用。还进一步研究了促炎基因表达以及ROS产生。结果如下：NBP预处理可明显改善肾功能，减轻病理损伤、炎症反应、氧化应激和细胞凋亡。因此，NBP减弱了H/R诱导的ROS、促炎基因表达、凋亡和切割的caspase-3水平在HK 2细胞中的增加。结论：本研究首次证实NBP可通过减轻炎症、氧化应激和细胞凋亡来改善肾IRI，提示NBP可能是抗阿基的良好候选药物。? 2021年，任作家。爱思唯尔公司出版这是一个在CC BY-NC-ND许可证下的开放获取文章（http：//creativecommons.org/licenses/by-nc-nd/4.0/）。
Background: Renal ischemia reperfusion injury (IRI) has become a growing concern in clinical practice with high morbidity and mortality rates. There is currently no effective prophylactic regimen available to prevent its occurrence and to improve its clinical prognosis. Dl-3-n-butylphthalide (NBP) has been used for stroke treatment in China for years. Little is known about its role in preventing kidney injury. Methods: The kidneys of male C57BL/6J mice were subjected to 33 min of ischemia followed by 24 h of reperfusion. NBP was administered by gavage prior to surgery. The reno-protective effect of NBP was evaluated by serum creatinine, kidney injury markers and renal pathological changes. Furthermore, the inflammation, oxidative stress, and apoptosis markers in kidney tissue were examined. In vitro, HK2 cells were treated prophylactically with NBP and then exposed to hypoxia/reoxygenation (H/R). Cell viability and apoptosis related protein were quantified to verify the protective effect of NBP. Pro-inflammation genes expression as well as ROS generation were further investigated also. Results: NBP pretreatment significantly improved renal dysfunction and alleviated pathological injury, renal inflammation response, oxidative stress and cell apoptosis. Consistently, NBP attenuated H/R induced increases in ROS, pro-inflammatory genes expression, apoptosis and cleaved caspase-3 levels in HK2 cells. Conclusion: Our promising results validated for the first time that NBP could ameliorate renal IRI via attenuating inflammation, oxidative stress, and apoptosis, which indicated that NBP might be a good candidate against AKI. ? 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).