器官移植2025，Vol.16Issue(2)：237-245,9.DOI:10.12464/j.issn.1674-7445.2024259
黄葵胶囊预处理人脐带间充质干细胞外泌体改善肾脏缺血-再灌注损伤的作用及机制
The effect and mechanism of Huangkui capsule pretreatment of human umbilical cord mesenchymal stem cell-derived exosomes on improving renal ischemia-reperfusion injury
摘要
Abstract
Objective To explore the effects and mechanisms of human umbilical cord mesenchymal stem cell(HUC-MSC)-derived exosomes(Exo)pretreated with Huangkui capsules on renal ischemia-reperfusion injury(IRI).Methods HUC-MSCs were cultured in media containing different concentrations of Huangkui capsules for 24 hours to determine cell viability and select an appropriate concentration for subsequent experiments.HUC-MSCs were pretreated with 50 μg/mL Huangkui capsules for 24 hours,and Exo were extracted using an exosome extraction kit.The morphology was observed under a transmission electron microscope,particle size was measured by nanoparticle tracking analysis,and the expression of exosomal membrane surface marker proteins was detected by Western blot.Human renal tubular epithelial cells(HK-2 cells)were randomly divided into hypoxia/reoxygenation group(M group),hypoxia/reoxygenation+Exo group(E group),and hypoxia/reoxygenation+Huangkui capsules pretreated Exo group(H group).Western blotting was used to measure the expression of endoplasmic reticulum stress(ERS)-related proteins,and real-time fluorescent quantitative reverse transcription polymerase chain reaction was used to measure the expression of ERS-related gene messenger RNA(mRNA).Mice were randomly divided into sham operation group(Sham group),ischemia-reperfusion group(I/R group),ischemia-reperfusion+Exo group(E group),and ischemia-reperfusion+Huangkui capsules pretreated Exo group(H group).Renal histological assessment,serum creatinine(Scr),blood urea nitrogen(BUN)measurement and inflammatory factor detection were performed 24 hours later.Results Both Exo and Huangkui capsules prereated Exo had a bilayer membrane structure and a cup-shaped morphology;their average particle sizes were 116.8 nm and 81.3 nm,respectively.Both expressed CD9,CD63,TSG101.Compared with the M group,the E group had decreased relative expression of transcription factor 6(ATF6)and protein kinase R-like endoplasmic reticulum kinase(PERK)proteins,increased mRNA relative expression,increased relative expression of C/EBP homologous protein(CHOP)protein,and decreased mRNA relative expression.Compared with the E group,the H group had decreased relative expression of ATF6,PERK,CHOP proteins,and decreased mRNA relative expression of ATF6 and PERK(all P<0.05).Animal experimental results showed that compared with the Sham group,the I/R group had increased renal tubular injury scores,Scr,BUN,interleukin(IL)-1β,IL-10,IL-18,tumor necrosis factor(TNF)-α levels.Compared with the I/R group,the E and H groups had decreased renal tubular injury scores and Scr,BUN,IL-1β,IL-10,IL-18,TNF-α levels.Compared with the E group,the H group had decreased renal tubular injury scores and Scr,BUN,IL-1β,IL-10,IL-18,TNF-α levels(all P<0.05).Conclusions Huangkui capsules pretreatment HUC-MSC-derived Exo may alleviate renal IRI by inhibiting ERS.关键词
肾移植/缺血-再灌注损伤/黄葵胶囊/人脐带间充质干细胞/外泌体/内质网应激/急性肾损伤/炎症因子Key words
Kidney transplantation/Ischemia-reperfusion injury/Huangkui capsule/Human umbilical cord mesenchymal stem cell/Exosome/Endoplasmic reticulum stress/Acute kidney injury/Inflammatory factor分类
医药卫生引用本文复制引用
姚雅韡,贺佳辉,王浩,王誉潼,王睿妍,万幸雨,刘雨佳,吕兴华..黄葵胶囊预处理人脐带间充质干细胞外泌体改善肾脏缺血-再灌注损伤的作用及机制[J].器官移植,2025,16(2):237-245,9.基金项目
甘肃省自然科学基金(23JRRA0932) （23JRRA0932）
