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Artesunate Restrains Maturation of Dendritic Cells and Ameliorates Heart Transplantation-Induced Acute Rejection in Mice through the PERK/ATF4/CHOP Signaling Pathway
Mediators of Inflammation ( IF 4.6 ) Pub Date : 2021-08-21 , DOI: 10.1155/2021/2481907 Yuanyang Chen 1, 2 , Sihao Zheng 1, 2 , Zhiwei Wang 1 , Xin Cai 1 , Yanjia Che 1, 2 , Qi Wu 1, 2 , Shun Yuan 1, 2 , Xiaohan Zhong 1, 2
Mediators of Inflammation ( IF 4.6 ) Pub Date : 2021-08-21 , DOI: 10.1155/2021/2481907 Yuanyang Chen 1, 2 , Sihao Zheng 1, 2 , Zhiwei Wang 1 , Xin Cai 1 , Yanjia Che 1, 2 , Qi Wu 1, 2 , Shun Yuan 1, 2 , Xiaohan Zhong 1, 2
Affiliation
Background. Heart transplantation (HT) is the only effective treatment for end-stage heart failure because it can effectively improve the survival rate and quality of life of patients with heart failure. Artesunate (ART) is an artemisinin derivative, with good water solubility and higher oral bioavailability. The main aim of this study was to determine the role of ART in HT mice. Methods. In animal experiments, mice were divided into the control group, HT group, low ART+HT group, and high ART+HT group. Next, inflammatory cell infiltration, oxidative stress injury, and myocardial cell apoptosis were determined in heart tissue. The proportion of multiple lymphocytes in spleen and lymph nodes was then determined using flow cytometry. In addition, cell experiments were conducted to determine the changes in expression of surface maturation markers of BMDC and changes in intracellular reactive oxygen species after LPS stimulation. Finally, western blot analysis was performed to determine the levels of endoplasmic reticulum stress-related proteins (CHOP/ATF4/PERK). Results. The survival time of mice in the ART treatment group was significantly prolonged and was positively correlated with the dose. In animal experiments, ART significantly reduced inflammatory cell infiltration in heart tissue and the proportion of CD4+CD8+ T cells in spleens and lymph nodes. Moreover, ART treatment lowered the 8-OHdg in hearts and myocardial apoptosis. In cell experiments, ART treatment slowed down the development and maturation of BMDCs by inhibiting the expression of endoplasmic reticulum stress-related proteins. Furthermore, the treatment alleviated the oxidative stress damage of BMDCs. Conclusion. ART can inhibit maturation of dendritic cells through the endoplasmic reticulum stress signaling pathway, thereby alleviating acute rejection in mice after heart transplantation.
中文翻译:
青蒿琥酯通过 PERK/ATF4/CHOP 信号通路抑制树突状细胞成熟并改善心脏移植诱导的小鼠急性排斥反应
背景。心脏移植(HT)是治疗终末期心力衰竭的唯一有效方法,因为它可以有效提高心力衰竭患者的生存率和生活质量。青蒿琥酯(ART)是一种青蒿素衍生物,具有良好的水溶性和较高的口服生物利用度。本研究的主要目的是确定 ART 在 HT 小鼠中的作用。方法. 动物实验将小鼠分为对照组、HT组、低ART+HT组、高ART+HT组。接下来,测定心脏组织中的炎症细胞浸润、氧化应激损伤和心肌细胞凋亡。然后使用流式细胞术确定脾脏和淋巴结中多个淋巴细胞的比例。此外,进行细胞实验以确定BMDC表面成熟标志物表达的变化和LPS刺激后细胞内活性氧的变化。最后,进行蛋白质印迹分析以确定内质网应激相关蛋白(CHOP/ATF4/PERK)的水平。结果. ART治疗组小鼠存活时间显着延长,且与剂量呈正相关。在动物实验中,ART 显着降低了心脏组织中的炎症细胞浸润以及脾脏和淋巴结中 CD4+CD8+T 细胞的比例。此外,ART 治疗降低了心脏中的 8-OHdg 和心肌细胞凋亡。在细胞实验中,ART 治疗通过抑制内质网应激相关蛋白的表达减缓了 BMDCs 的发育和成熟。此外,该处理减轻了BMDCs的氧化应激损伤。结论。ART可通过内质网应激信号通路抑制树突状细胞的成熟,从而减轻小鼠心脏移植后的急性排斥反应。
更新日期:2021-08-21
中文翻译:
青蒿琥酯通过 PERK/ATF4/CHOP 信号通路抑制树突状细胞成熟并改善心脏移植诱导的小鼠急性排斥反应
背景。心脏移植(HT)是治疗终末期心力衰竭的唯一有效方法,因为它可以有效提高心力衰竭患者的生存率和生活质量。青蒿琥酯(ART)是一种青蒿素衍生物,具有良好的水溶性和较高的口服生物利用度。本研究的主要目的是确定 ART 在 HT 小鼠中的作用。方法. 动物实验将小鼠分为对照组、HT组、低ART+HT组、高ART+HT组。接下来,测定心脏组织中的炎症细胞浸润、氧化应激损伤和心肌细胞凋亡。然后使用流式细胞术确定脾脏和淋巴结中多个淋巴细胞的比例。此外,进行细胞实验以确定BMDC表面成熟标志物表达的变化和LPS刺激后细胞内活性氧的变化。最后,进行蛋白质印迹分析以确定内质网应激相关蛋白(CHOP/ATF4/PERK)的水平。结果. ART治疗组小鼠存活时间显着延长,且与剂量呈正相关。在动物实验中,ART 显着降低了心脏组织中的炎症细胞浸润以及脾脏和淋巴结中 CD4+CD8+T 细胞的比例。此外,ART 治疗降低了心脏中的 8-OHdg 和心肌细胞凋亡。在细胞实验中,ART 治疗通过抑制内质网应激相关蛋白的表达减缓了 BMDCs 的发育和成熟。此外,该处理减轻了BMDCs的氧化应激损伤。结论。ART可通过内质网应激信号通路抑制树突状细胞的成熟,从而减轻小鼠心脏移植后的急性排斥反应。