Rao Kaihua, Li Zhengfeng, Huang Chunhua
Department of Neurology, Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine Nanchang 330006, Jiangxi, China.
Department of Endocrinology, Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine Nanchang 330006, Jiangxi, China.
Am J Transl Res. 2025 Aug 15;17(8):6333-6346. doi: 10.62347/CYDE1809. eCollection 2025.
Myasthenia gravis (MG), a chronic autoimmune neuromuscular disorder characterized by muscle weakness, remains a therapeutic challenge. This study aimed to evaluate the efficacy of the traditional Chinese herbal formulation YiQiWenShen (YQWS) in comparison with prednisone in a rat model of experimental autoimmune myasthenia gravis (EAMG), with the goal of exploring new therapeutic strategies.
EAMG was induced in rats, who were subsequently treated with different doses of YQWS and prednisone. Clinical severity was assessed using the Baggi scoring system, alongside measurements of body weight, serum acetylcholine receptor antibody (AChR-Ab) levels, and splenic lymphocyte proliferation in response to the rat AChRα97-116 peptide and concanavalin A. Cytokine profiles, proportions of T follicular helper (Tfh) cells, T follicular regulatory (Tfr) cells, and germinal center B (GC)-B cells in lymph nodes were analyzed using enzyme-linked immunosorbent assay and flow cytometry. The expression levels of B-cell lymphoma 6 (Bcl-6) mRNA and protein were analyzed using quantitative real-time polymerase chain reaction and western blot, respectively.
After EAMG induction, the rats exhibited significant weight loss, elevated clinical scores, and increased AChR-Ab levels. Both YQWS and prednisone treatments significantly improved body weight and clinical scores, and reduced serum AChR-Ab levels. YQWS also attenuated the increased splenic lymphocyte proliferation. Cytokine dysregulation observed in EAMG rats was partially corrected following YQWS treatment. Furthermore, both YQWS and prednisone effectively normalized the Tfh/Tfr cell ratio, decreased GC-B cell populations, and downregulated Bcl-6 expression.
YQWS exerts therapeutic effects in EAMG comparable to those of prednisone, demonstrating its potential as an alternative treatment for MG. Its efficacy is associated with the normalization of body weight, modulation of immune responses, correction of cytokine imbalances and reestablishment of Tfh/Tfr and GC-B cell homeostasis.
重症肌无力（MG）是一种以肌肉无力为特征的慢性自身免疫性神经肌肉疾病，仍然是一个治疗挑战。本研究旨在评估中药制剂益气温肾（YQWS）与泼尼松在实验性自身免疫性重症肌无力（EAMG）大鼠模型中的疗效，以探索新的治疗策略。
诱导大鼠发生EAMG，随后用不同剂量的YQWS和泼尼松进行治疗。使用Baggi评分系统评估临床严重程度，同时测量体重、血清乙酰胆碱受体抗体（AChR-Ab）水平，以及脾淋巴细胞对大鼠AChRα97-116肽和伴刀豆球蛋白A的增殖反应。使用酶联免疫吸附测定和流式细胞术分析淋巴结中细胞因子谱、T滤泡辅助（Tfh）细胞、T滤泡调节（Tfr）细胞和生发中心B（GC）-B细胞的比例。分别使用定量实时聚合酶链反应和蛋白质印迹分析B细胞淋巴瘤6（Bcl-6）mRNA和蛋白的表达水平。
EAMG诱导后，大鼠体重显著减轻、临床评分升高、AChR-Ab水平增加。YQWS和泼尼松治疗均显著改善了体重和临床评分，并降低了血清AChR-Ab水平。YQWS还减弱了脾淋巴细胞增殖的增加。YQWS治疗后，EAMG大鼠中观察到的细胞因子失调得到部分纠正。此外，YQWS和泼尼松均有效使Tfh/Tfr细胞比例正常化，减少GC-B细胞群体，并下调Bcl-6表达。
YQWS在EAMG中发挥的治疗作用与泼尼松相当，证明其作为MG替代治疗的潜力。其疗效与体重正常化、免疫反应调节、细胞因子失衡纠正以及Tfh/Tfr和GC-B细胞稳态的重建有关。
