摘要
目的 探讨环泊酚对减轻肾缺血再灌注损伤的作用及机制.方法 建立SD大鼠肾缺血再灌注模型,单独或联合应用环泊酚、铁死亡抑制剂Fer-1及铁死亡激动剂Erastin干预造模大鼠,24 h后处死,取大鼠心脏血液检测肌酐及尿素氮,同时取大鼠肾,部分行苏木精和伊红染色及Paller评分评估大鼠肾损伤程度,另一部分检测铁死亡相关指标活性氧、谷胱甘肽、Fe2+、丙二醛水平及胱氨酸/谷氨酸反向转运蛋白的主要亚基SLC7A11与下游功能蛋白GPX4的表达水平及转录水平.结果 与模型组相比,环泊酚组与Fer-1组肾损伤指标血肌酐、血尿素氮及Paller评分、活性氧、亚铁离子、丙二醛水平较低(P<0.05);与模型组相比,环泊酚组谷胱甘肽、SLC7A11、GPX4水平,及SLC7A11、GPX4相关基因表达水平较高;与环泊酚组相比,环泊酚+Erastin组上述各项指标较低(P<0.05).结论 环泊酚可以减轻肾缺血再灌注损伤,其机制与System Xc-/GPX4通路有关.
Abstract
Objective To investigate the protective effect of Ciprofol on renal ischemia-reperfusion injury and its mechanism.Methods The established renal ischemia-reperfusion model of SD rats was intervened by several drugs besides Ciprofol,ferrostatin-1(inhibitor of ferroptosis)and Erastin(agonist of ferroptosis)alone or in combination.After 24 hours,the rats were sacrificed under anesthesia,and their heart blood taken to detect creatinine and urea nitrogen to evaluate the renal function.At the same time,the kidneys of rats were taken,part of which stained with hematoxylin-eosin staining and the paller score was used to evaluate the degree of renal pathological damage in rats.The other part was used to detect the level of ferroptosis-related indicators of reactive oxygen species,glutathione,ferrous iron,malondialdehyde,the expression and tran-scription level of SLC7A11,the main subunit of SystemXc-,and the downstream functional protein GPX4.Results Compared with the control group,the levels of creatinine,urea nitrogen,paller score,reactive oxygen speciesferrous iron,malondialdehyde in the Ciprofol and Fer-1 group were lower(P<0.05).Compared with the control group,the levels of glutathione,SLC7A11,GPX4 in the Ciprofol group were higher;besides,the expression levels of SLC7A11 and GPX4 related genes were higher in the Ciprofol group(P<0.05).Com-pared with the Ciprofol group,the levels of glutathione,SLC7A11,GPX4 and the expression levels of SLC7A11 and GPX4 related genes were lower in the Ciprofol+Erastin group(P<0.05).Conclusion Ciprofol can reduce renal ischemia-reperfusion injury to protect the kidney,and the mechanism is related to the System-Xc-/GPX4 pathway.
基金项目
甘肃省自然科学基金(23JRRA0932)
甘肃省重点人才项目(2021RCXM002)
兰州大学第一医院院内项目(ldyyyn2020-106)
兰州大学第一医院院内项目(ldyyyn2022-1)
兰州大学医学教育创新发展项目(lzuyxcx-2022-130)
国家科技期刊平台
NSTL
万方数据