Jing Feng, Yang Fei, Cui Fang, Chen Zhaohui, Ling Li, Huang Xusheng
Department of Neurology, Chinese PLA General Hospital, Beijing 100853, China.
Department of Neurology, The 309th Hospital of Chinese PLA, Beijing 100091, China.
Biosci Rep. 2017 Jul 16;37(4). doi: 10.1042/BSR20170767. Print 2017 Aug 31.
Myasthenia gravis (MG) is an autoimmune disease commonly treated with immunosuppressants. We evaluated the novel immunosuppressant, rapamycin (RAPA), in a rat model of experimental autoimmune MG (EAMG). Mortality rates in the RAPA (12%) were significantly down compared with the EAMG (88%) or cyclophosphamide (CTX) (68%) intervention groups. Muscular weakness decreased after both RAPA and CTX treatment. However, Lennon scores were lower (1.74 ± 0.49, 3.39 ± 0.21, and 3.81 ± 0.22 in RAPA, CTX, and EAMG groups, respectively), and body weights (203.12 ± 4.13 g, 179.23 ± 2.13 g, and 180.13 ± 5.13 g in RAPA, CTX, and EAMG groups, respectively) were significantly higher, only in the RAPA group. The proportion of regulatory T cells (Treg) significantly increased, while that of Th17 cells significantly decreased in the RAPA group compared with the EAMG group. In comparison, CTX intervention resulted in increased Th17 but significantly decreased Tregs. Hence, RAPA can be more effectively used in comparison with CTX to treat MG, with an efficacy higher than that of CTX. In addition, our results suggest RAPA's efficacy in alleviating symptoms of MG stems from its ability to correct the Treg/Th17 imbalance observed in MG.
重症肌无力（MG）是一种通常用免疫抑制剂治疗的自身免疫性疾病。我们在实验性自身免疫性重症肌无力（EAMG）大鼠模型中评估了新型免疫抑制剂雷帕霉素（RAPA）。与EAMG干预组（88%）或环磷酰胺（CTX）干预组（68%）相比，RAPA组的死亡率（12%）显著降低。RAPA和CTX治疗后肌无力均有所减轻。然而，只有RAPA组的Lennon评分较低（RAPA组、CTX组和EAMG组分别为1.74±0.49、3.39±0.21和3.81±0.22），且体重显著更高（RAPA组、CTX组和EAMG组分别为203.12±4.13 g、179.23±2.13 g和180.13±5.13 g）。与EAMG组相比，RAPA组调节性T细胞（Treg）比例显著增加，而Th17细胞比例显著降低。相比之下，CTX干预导致Th17增加，但Treg显著减少。因此，与CTX相比，RAPA可更有效地用于治疗MG，其疗效高于CTX。此外，我们的结果表明，RAPA缓解MG症状的疗效源于其纠正MG中观察到的Treg/Th17失衡的能力。
