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青蒿琥酯通过调节Th17/Treg平衡减轻慢性移植物抗宿主病

[Artesunate attenuate chronic graft-versus-host disease by regulating Th17/Treg balance].

作者信息

Chen X M, Weng J Y, Lai P L, Wang Y L, Huang X, Geng S X, Guo L Y, Huang T, Zeng L J, Du X

机构信息

Department of Hematology, Guangdong General Hospital/Guangdong Academy of Medical Sciences, Guangdong Geriatrics Institute, Guangzhou 510080, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2019 Jan 14;40(1):63-68. doi: 10.3760/cma.j.issn.0253-2727.2019.01.012.

Abstract

To investigate the effects of artesunate treatment on chronic graft-versus-host disease (cGVHD). Recipient BALB/c mice received 8 × 10(6) bone marrow cells with 8×10(6) spleen cells from B10D2 mice. Artesunate solubilized in acetone was injected intraperitoneally every day at the dose of 1 mg/kg at Day 28 after BMT. The clinical scores, survival and histopathological damage were analyzed. The frequency of Th17 and Tregs in PB and spleens from the mice were evaluated by flow cytometry. In addition, CD4(+) T cells from the spleens of mice were cultured in vitro, then stimulated with artesunate, the frequency of Th17 and Tregs in these splenocytes were evaluated by flow cytometry. Artesunate administration diminished clinical and histopathological damage, and improved the survival of cGVHD mice[(46.57±7.83)% (55.71±6.99)%, (2)=5.457, =0.020]; Artesunate contributed to Tregs development [(4.45±0.04)% (8.40±0.23)%, =15.679, <0.001; (6.62±0.24)% (10.48±0.48)%, =6.587, =0.003] while decreased Th17 cells [(1.51±0.18)% (0.58±0.19)%, =7.233, <0.001; (1.48±0.38)% (0.71±0.18)%, =3.653, =0.011] expressions in both PB and spleens, and decreased the Th17/Treg ratio (0.34±0.05 0.09±0.03, =7.621, =0.002; 0.19±0.03 0.06±0.02, =6.993, =0.002). Moreover, artesunate suppressed the Th17 cells expressions [(0.82±0.37) % (3.39±1.22) %, =4.044, =0.007] and contributed to Tregs development [(34.63±1.29) % (14.28±1.69) %, =19.119, <0.001], and also decreased the Th17/Treg ratio (0.24±0.09 0.02±0.01, =4.780, =0.003) . Artesunate suppressed the Th17 cells expressions and contributed to Tregs development, which provided new sights into the development of a novel drug for cGVHD, e.g., artemisinin.

摘要

为研究青蒿琥酯治疗慢性移植物抗宿主病(cGVHD)的效果。受体BALB/c小鼠接受来自B10D2小鼠的8×10⁶个骨髓细胞和8×10⁶个脾细胞。在骨髓移植后第28天,将溶于丙酮的青蒿琥酯以1mg/kg的剂量每天腹腔注射。分析临床评分、生存率和组织病理学损伤。通过流式细胞术评估小鼠外周血和脾脏中Th17和调节性T细胞(Tregs)的频率。此外,将小鼠脾脏中的CD4⁺T细胞体外培养,然后用青蒿琥酯刺激,通过流式细胞术评估这些脾细胞中Th17和Tregs的频率。青蒿琥酯给药减轻了cGVHD小鼠的临床和组织病理学损伤,并提高了其生存率[(46.57±7.83)% (55.71±6.99)%,t = 5.457,P = 0.020];青蒿琥酯促进了Tregs的发育[(4.45±0.04)% (8.40±0.23)%,t = 15.679,P < 0.001;(6.62±0.24)% (10.48±0.48)%,t = 6.587,P = 0.003],同时降低了外周血和脾脏中Th17细胞的表达[(1.51±0.18)% (0.58±0.19)%,t = 7.233,P < 0.001;(1.48±0.38)% (0.71±0.18)%,t = 3.653,P = 0.011],并降低了Th17/Treg比值(0.34±0.05 0.09±0.03,t = 7.621,P = 0.002;0.19±0.03 0.06±0.02,t = 6.993,P = 0.002)。此外,青蒿琥酯抑制了Th17细胞的表达[(0.82±0.37)% (3.39±1.22)%,t = 4.044,P = 0.007],促进了Tregs的发育[(34.63±1.29)% (14.28±1.69)%,t = 19.119,P < 0.001],并且也降低了Th17/Treg比值(0.24±0.09 0.02±0.01,t = 4.780,P = 0.003)。青蒿琥酯抑制Th17细胞的表达并促进Tregs的发育,这为开发用于cGVHD的新型药物(如青蒿素)提供了新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a8/7351699/80fc9aefac24/cjh-40-01-063-g001.jpg

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