Department of Internal Medicine Neurology, Fujian Putian First Hospital, Putian, Fujian 351100, P.R. China.
Department of Internal Medicine Neurology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350004, P.R. China.
Mol Med Rep. 2017 Dec;16(6):8283-8288. doi: 10.3892/mmr.2017.7627. Epub 2017 Sep 26.
Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease mediated by CD4+ T cells. It is characterized by mononuclear cell infiltration around the small blood vessels in the central nervous system (CNS). Previous investigations have found that apoptosis is associated with the occurrence and development of autoimmune disease, and that mononuclear cell apoptosis and clearance from the CNS is one of the repair mechanisms of EAE. Tripterygium wilfordii glycoside (TWP) is an organic matter isolated from Tripterygium wilfordii, which has anti‑inflammatory and immunosuppressive effects. In the present study, male Lewis rats were randomly divided into a normal control, EAE and TWP groups. Rats in EAE and TWP groups received injections of emulsified EAE antigen (myelin protein) at two points on the footpad while control group received PBS. The TWP group was then treated with TWP daily for 21 days. Symptoms and nerve function scores were observed and evaluated. Specimens of blood, brain and spinal cord were collected for further pathological examination, Tunel assay, ELISA and immunohistochemistry were performed to examine the effect of TWP on the onset of EAE, and changes in CNS inflammatory infiltration, cell apoptosis, and the expression of nuclear factor (NF)‑κB P65 and interleukin (IL)‑2. The results showed that the TWP treatment group exhibited decreased EAE and delayed onset, compared with the control. The clinical symptoms were significantly reduced and alleviation of inflammatory cell infiltration was observed. Compared with the EAE group, a higher inflammatory cell apoptotic rate, and reduced serum levels of IL‑2 and NF‑κB p65‑positive cells were observed in the TWP treatment group. Therefore, TWP effectively inhibited EAE via the inhibition of CNS inflammatory cell infiltration, enhancement of inflammatory cell apoptosis, and downregulation of the expression of NF‑κB and IL‑2.
实验性自身免疫性脑脊髓炎（EAE）是一种由 CD4+T 细胞介导的自身免疫性疾病。其特征是中枢神经系统（CNS）中小血管周围有单核细胞浸润。先前的研究发现，细胞凋亡与自身免疫性疾病的发生和发展有关，而单核细胞凋亡和从中枢神经系统清除是 EAE 修复机制之一。雷公藤多苷（TWP）是从雷公藤中分离得到的一种有机物，具有抗炎和免疫抑制作用。在本研究中，雄性 Lewis 大鼠随机分为正常对照组、EAE 组和 TWP 组。EAE 组和 TWP 组大鼠在足底两点注射乳化 EAE 抗原（髓鞘蛋白），对照组大鼠注射 PBS。然后 TWP 组每日给予 TWP 治疗 21 天。观察并评估症状和神经功能评分。采集血液、脑和脊髓标本进行进一步的病理检查，通过 TUNEL 检测、ELISA 和免疫组织化学法检测 TWP 对 EAE 发病的影响以及对 CNS 炎症浸润、细胞凋亡、核因子（NF）-κB P65 和白细胞介素（IL）-2 表达的变化。结果显示，与对照组相比，TWP 治疗组 EAE 发病延迟，症状减轻，炎症细胞浸润减轻。与 EAE 组相比，TWP 治疗组炎症细胞凋亡率较高，血清中 IL-2 和 NF-κB p65 阳性细胞减少。因此，TWP 通过抑制 CNS 炎症细胞浸润、增强炎症细胞凋亡以及下调 NF-κB 和 IL-2 的表达，有效抑制 EAE。
