1 Department of Ophthalmology, Changsha Aier Eye Hospital, Aier School of Ophthalmology, Central South University, Changsha, China.
2 Department of Ophthalmology, Huaihe Hospital of Henan University, Kaifeng, China.
Int J Immunopathol Pharmacol. 2018 Jan-Dec;32:394632017751547. doi: 10.1177/0394632017751547.
Total glucosides of paeony (TGP) are active components extracted from the roots of Paeonia lactiflora Pall. In this study, we investigated the role and mechanisms of TGP in experimental autoimmune uveitis (EAU) model of mice. The C57BL/6 mice were randomly divided into three groups: sham group, EAU-control group, and EAU-TGP group. Clinical score of images of the eye fundus were taken on 7, 14, 21, and 28 days after induction of EAU. The concentrations of proinflammatory cytokines in intraocular fluid were measured at 14 days after EAU induction with the use of a multiplex assay system. Flow cytometry was used to analyze the frequency of CD4+, CD8+, interferon-gamma (IFN-γ), and CD4+/CD8+ ratio in spleen and lymph nodes. Western blotting was used to measure expressions of mitogen-activated protein kinase (MAPK) pathway-related proteins in retina. Clinical scores for uveitis were lower in TGP-treated EAU mice than those without TGP treatment. Importantly, the concentrations of cytokines induced by T-helper 1 (Th1) and T-helper 2 (Th2) cells in intraocular fluid were reduced in EAU mice treated with TGP. Furthermore, the frequency of CD4+, IFN-γ, and CD4+/CD8+ ratio was decreased and the frequency of CD8+ was increased in spleen and lymph nodes of mice treated with TGP. The anti-inflammatory effects of TGP were mediated by inhibiting the MAPK signaling pathways. Our results showed that TGP suppressed uveitis in mice via the inhibition of Th1 and Th2 cell function. Thus, TGP may be a promising therapeutic strategy for uveitis, as well as other ocular inflammatory diseases.
白芍总苷（TGP）是从芍药根中提取的有效成分。本研究探讨了 TGP 在实验性自身免疫性葡萄膜炎（EAU）小鼠模型中的作用及机制。C57BL/6 小鼠随机分为三组：假手术组、EAU 对照组和 EAU-TGP 组。在 EAU 诱导后第 7、14、21 和 28 天，通过眼底图像采集眼内炎症的临床评分。在 EAU 诱导后第 14 天，采用多重检测系统测量眼内液中促炎细胞因子的浓度。采用流式细胞术分析脾和淋巴结中 CD4+、CD8+、干扰素-γ（IFN-γ）和 CD4+/CD8+比值的频率。Western blot 法检测视网膜丝裂原活化蛋白激酶（MAPK）通路相关蛋白的表达。与未用 TGP 治疗的 EAU 小鼠相比，用 TGP 治疗的 EAU 小鼠的葡萄膜炎临床评分较低。重要的是，用 TGP 治疗的 EAU 小鼠眼内液中由 Th1 和 Th2 细胞诱导的细胞因子浓度降低。此外，TGP 治疗的小鼠脾和淋巴结中 CD4+、IFN-γ和 CD4+/CD8+比值降低，CD8+频率增加。TGP 的抗炎作用是通过抑制 MAPK 信号通路介导的。我们的结果表明，TGP 通过抑制 Th1 和 Th2 细胞功能抑制了小鼠葡萄膜炎。因此，TGP 可能是葡萄膜炎以及其他眼部炎症性疾病有前途的治疗策略。
