腹膜纤维化与血浆/腹透液中分泌型PDL1水平的相关性研究  

Study on the correlation between peritoneal fibrosis and the level of secreted PDL1 in plasma/peritoneal fluid

作　　者：张云朝 何丽洁 ZHANG Yunchao;HE Lijie(Department of Nephrology,Xijing Hospital,Air Force Medical University,Xi'an 710032,China)

机构地区：[1]空军军医大学西京医院肾脏内科,陕西西安710032

出　　处：《空军军医大学学报》2024年第5期542-548,共7页Journal of Air Force Medical University

基　　金：国家自然科学基金(81770764)。

摘　　要：目的探讨免疫检查点程序性细胞死亡配体1(PDL1)的分泌形式可溶性细胞程序性死亡配体1(sPDL1)与腹膜纤维化(PF)进展的相关性。方法对不同腹膜透析(PD)时长、不同PF程度的PD患者进行观察,检测PD脱落细胞PDL1表达、血浆和PD液中的sPDL1分泌情况;使用腹膜间皮细胞(HPMC)建立高糖纤维化模型并用慢病毒进行PDL1下调处理,评估PDL1/sPDL1与间皮细胞转分化的相关性。结果PD治疗之后sPDL1显著上调;与PD液sPDL1相比,血浆sPDL1与原发疾病等因素具有相关性;PD液sPDL1与PF水平呈正相关;高水平sPDL1患者更易进入腹膜功能下一阶段;PD液sPDL1与脱落细胞PDL1表达呈正相关;在高糖刺激下,PDL1及sPDL1在HPMC中的表达显著升高,随后α-SMA和snail的表达上调;慢病毒下调PDL1及sPDL1后,间皮细胞α-SMA及snail相应下调。结论PD液sPDL1与PD治疗的相关性较高;PD液sPDL1的增高可能为纤维化的早期征兆,提示腹膜溶质转运功能的升高;高糖诱导下,sPDL1在HPMC中过表达,促进细胞转分化,诱导PF的进展。Objective To investigate the correlation between the secreted form of immune checkpoint programmed cell death ligand 1(PDL1)—soluble programmed cell death ligand 1(sPDL1)and the progression of peritoneal fibrosis(PF).Methods Peritoneal dialysis(PD)patients with different PD duration and PF degree were observed to detect the expression of PDL1 in exfoliated cells and the secretion of sPDL1 in plasma and PD fluid.Human peritoneal mesothelial cells(HPMC)were used to establish high glucose fibrosis model and lentivirus was used to down-regulate PDL1,and the correlation between PDL1/sPDL1 and mesothelial cell transdifferentiation was evaluated.Results sPDL1 was significantly up-regulated after PD treatment.Compared with PD fluid sPDL1,plasma sPDL1 was correlated with primary diseases and other factors.There was a positive correlation between PD fluid sPDL1 and PF level.Patients with high levels of sPDL1 were more likely to progress to the next stage of peritoneal function.There was a positive correlation between sPDL1 expression in PD fluid and PDL1 expression in exfoliated cells.Under high glucose stimulation,the expressions of PDL1 and sPDL1 were significantly increased in HPMC,and then the expressions ofα-SMA and snail were up-regulated.After lentivirus down-regulation of PDL1 and sPDL1,α-SMA and snail in mesothelial cells were down-regulated accordingly.Conclusion PD fluid sPDL1 has a high correlation with PD treatment.The increase of sPDL1 in PD fluid may be an early sign of fibrosis,indicating the increase of peritoneal solute transport function.Under the induction of high glucose,sPDL1 is overexpressed in HPMC,which promotes cell transdifferentiation and induces the progression of PF.

关 键 词：腹膜炎 腹膜纤维化 转分化 PDL1 sPDL1 

分 类 号：R459.5[医药卫生—治疗学]