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酸枣仁皂苷 A 通过上调 IDO 表达抑制氧化应激损伤并增强人脐带间充质干细胞的免疫调节能力。

Jujuboside A inhibits oxidative stress damage and enhances immunomodulatory capacity of human umbilical cord mesenchymal stem cells through up-regulating IDO expression.

机构信息

School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China.

Department of Neurology, Dalian Municipal Central Hospital Affiliated to Dalian Medical University, Dalian 116033, China.

出版信息

Chin J Nat Med. 2022 Jul;20(7):494-505. doi: 10.1016/S1875-5364(22)60176-6.

Abstract

Impaired immunomodulatory capacity and oxidative stress are the key factors limiting the effectiveness of mesenchymal stem cell transplantation therapy. The present study was aimed to investigate the effects of jujuboside A (JuA) on the protective effect and immunomodulatory capacity of human umbilical cord mesenchymal stem cells (hUC-MSCs). Hydrogen peroxide was used to establish an oxidative damage model of hUC-MSCs, while PBMCs isolated from rats were used to evaluate the effect of JuA pre-treatment on the immunomodulatory capacity of hUC-MSCs. Furthermore, Hoechst 33258 staining, lactate dehydrogenase test, measurement of malondialdehyde, Western blot, high-performance liquid chromatography; and flow cytometry were performed. Our results indicated that JuA (25 μmol·L) promoted the proliferation of hUC-MSCs, but did not affect the differentiating capability of these cells. JuA pre-treatment inhibited apoptosis, prevented oxidative damage, and up-regulated the protein expression of nuclear factor-erythroid factor 2-related factor 2 and heme oxygenase 1 in hUC-MSCs in which oxidative stress was induced with HO. In addition, JuA pre-treatment enhanced the inhibitory effect of hUC-MSCs against abnormally activated PBMCs, which was related to stimulation of the expression and activity of indoleamine 2,3-dioxygenase. In conclusion, our results demonstrate that JuA pre-treatment can enhance the survival and immunomodulatory ability through pathways related to oxidative stress, providing a new option for the improvement of hUC-MSCs in the clinical setting.

摘要

免疫调节能力受损和氧化应激是限制间充质干细胞移植治疗效果的关键因素。本研究旨在探讨京尼平苷 A(JuA)对人脐带间充质干细胞(hUC-MSCs)保护作用和免疫调节能力的影响。本研究采用过氧化氢建立 hUC-MSCs 氧化损伤模型,采用大鼠分离的 PBMC 评估 JuA 预处理对 hUC-MSCs 免疫调节能力的影响。此外,还进行了 Hoechst 33258 染色、乳酸脱氢酶试验、丙二醛测定、Western blot、高效液相色谱和流式细胞术检测。结果表明,JuA(25 μmol·L)促进 hUC-MSCs 增殖,但不影响其分化能力。JuA 预处理可抑制 hUC-MSCs 凋亡,防止氧化损伤,并上调 HO 诱导的 hUC-MSCs 中核因子-红细胞 2 相关因子 2 和血红素加氧酶 1 的蛋白表达。此外,JuA 预处理增强了 hUC-MSCs 对异常激活的 PBMCs 的抑制作用,这与吲哚胺 2,3-双加氧酶的表达和活性刺激有关。综上所述,我们的研究结果表明,JuA 预处理可以通过与氧化应激相关的途径增强间充质干细胞的存活和免疫调节能力,为改善临床 hUC-MSCs 提供了新的选择。

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