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双氢青蒿素通过恢复 Treg/Th17 平衡来减轻系统性红斑狼疮小鼠模型的症状。

Dihydroartemisinin attenuated the symptoms of mice model of systemic lupus erythematosus by restoring the Treg/Th17 balance.

机构信息

Department of Dermatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

The First Clinical Academy, Guangzhou University of Chinese Medicine, Guangzhou, China.

出版信息

Clin Exp Pharmacol Physiol. 2021 Apr;48(4):626-633. doi: 10.1111/1440-1681.13461. Epub 2021 Jan 19.

Abstract

The Treg/Th17 imbalance is associated with the development of systemic lupus erythematosus (SLE). Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, is isolated from the traditional Chinese herb Artemisia annua Artemisia annua L. This study aims to evaluate the effects of DHA alone or in combination with prednisone in immunodeficiency of SLE. In vivo, the therapeutical effect of DHA alone or in combination with prednisone was assessed in the pristane-induced SLE mouse model. Then, the level of serum antibodies, creatinine (Cre), blood urea nitrogen (BUN), urine protein, kidney histopathology, interleukin (IL)-17, IL-6, transforming growth factor (TGF)-β, the expression of RORγt and Foxp3, the percentages of Treg and Th17 in peripheral blood and spleen were assayed. In vitro, the mouse spleen lymphocytes were separated and treated with DHA alone or DHA in combination with prednisone. Then the percentages of Treg and Th17, the concentration of IL-17, IL-6, TGF-β, and the expression of RORγt and Foxp3 were assayed. It was shown that DHA alone or in combination with prednisone treatment significantly alleviated the manifestations of pristane-induced SLE mice, suppressed inflammation and restored the Treg/Th17 balance. DHA alone or in combination with prednisone significantly inhibited Th17 cell differentiation while induced Treg cell differentiation in vitro. DHA alone or in combination with prednisone also reduced the transcription of RORγt and increased Foxp3 in lymphocytes, as well as IL-17 and TGF-β levels. Our data indicated that DHA can produce synergistic effect with prednisone to attenuate the symptoms of SLE by restoring Treg/Th17 balance.

摘要

Treg/Th17 失衡与系统性红斑狼疮(SLE)的发展有关。二氢青蒿素(DHA)是从传统中药青蒿中分离出来的青蒿素的半合成衍生物。本研究旨在评估 DHA 单独或与泼尼松联合应用于 SLE 免疫缺陷的疗效。在体内,采用角鲨烷诱导的 SLE 小鼠模型评估 DHA 单独或与泼尼松联合应用的治疗效果。然后,检测血清抗体、肌酐(Cre)、血尿素氮(BUN)、尿蛋白、肾脏组织病理学、白细胞介素(IL)-17、IL-6、转化生长因子(TGF)-β、RORγt 和 Foxp3 的表达、外周血和脾脏中 Treg 和 Th17 的百分比。在体外,分离小鼠脾淋巴细胞,用 DHA 单独或 DHA 联合泼尼松处理。然后检测 Treg 和 Th17 的百分比、IL-17、IL-6、TGF-β的浓度以及 RORγt 和 Foxp3 的表达。结果表明,DHA 单独或联合泼尼松治疗可显著缓解角鲨烷诱导的 SLE 小鼠的临床表现,抑制炎症反应,恢复 Treg/Th17 平衡。DHA 单独或联合泼尼松可显著抑制 Th17 细胞分化,诱导 Treg 细胞分化。DHA 单独或联合泼尼松还可降低淋巴细胞中 RORγt 的转录,增加 Foxp3 的表达,并降低 IL-17 和 TGF-β的水平。我们的数据表明,DHA 可与泼尼松产生协同作用,通过恢复 Treg/Th17 平衡来减轻 SLE 的症状。

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