Shan Wenjun, Zhu Xiaoyu, Qi Jieying, Hu Fang, Li Changzheng, Nie Xiaoli
School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2020 Nov 30;40(11):1682-1688. doi: 10.12122/j.issn.1673-4254.2020.11.23.
To explore the mechanism of decoction (XWGD) decoction in treating rheumatoid arthritis (RA) in mice.
Healthy male DBA/1 mice were used for CIA modeling. Twenty-five CIA mice with successful modeling and similar arthritis index (AI) scores were randomized equally into model group (CIA), methotrexate (MTX) group, and low-, medium-, and high-dose XWGD groups (0.975, 1.95, and 3.9 g/mL, respectively), with another 5 normal mice as the normal control group. The mice in normal control and CIA groups were given saline once a day, those in MTX group were given 0.1 mg/mL MTX once a week, and those in XWGD groups were treated daily via garage of XWGD containing crude drugs of different doses for 28 consecutive days. The AI score and HE staining were used to evaluate the changes in the joints of the CIA mice. The effect of XWGD on Th1, Th17, MDSC, G-MDSC and M-MDSC cells were evaluated with flow cytometry.
Treatment with MTX and different doses of XWGD significantly decreased the AI score of the mice and relieved joint inflammation as compared with the model group ( < 0.05), and a higher dose of XWGD decoction produced a stronger therapeutic effect. Compared with those in CIA model group, the mice in MTX and XWGD treatment groups showed significantly decreased percentages of Th1, Th17 and M-MDSC cells in the spleen and increased percentages of G-MDSC cells ( < 0.01), and these changes were more conspicuous with a higher dose of XWGD. Correlation analysis showed that Th1 and Th17 cells were positively correlated with M-MDSC and negatively correlated with G-MDSC cells ( < 0.01).
XWGD can improve joint inflammation in CIA mice by increasing the percentages of G-MDSC cells and decreasing the percentages of M-MDSC, Th1 and Th17 cells, and a high dose of XWGD can produce an equivalent therapeutic effect to methotrexate but with better safety.
探讨消萎固督汤(XWGD)治疗小鼠类风湿性关节炎(RA)的机制。
选用健康雄性DBA/1小鼠进行胶原诱导性关节炎(CIA)建模。将25只建模成功且关节炎指数(AI)评分相近的CIA小鼠随机均分为模型组(CIA)、甲氨蝶呤(MTX)组、消萎固督汤低、中、高剂量组(分别为0.975、1.95和3.9 g/mL),另取5只正常小鼠作为正常对照组。正常对照组和CIA组小鼠每天给予生理盐水,MTX组小鼠每周给予0.1 mg/mL MTX,消萎固督汤组小鼠连续28天每天经灌胃给予含不同剂量生药的消萎固督汤。采用AI评分和苏木精-伊红(HE)染色评估CIA小鼠关节的变化。采用流式细胞术评估消萎固督汤对Th1、Th17、髓源抑制细胞(MDSC)、粒细胞-髓源抑制细胞(G-MDSC)和单核细胞-髓源抑制细胞(M-MDSC)的影响。
与模型组相比,MTX及不同剂量消萎固督汤治疗均显著降低小鼠AI评分,减轻关节炎症(P<0.05),且消萎固督汤高剂量组疗效更强。与CIA模型组相比,MTX组和消萎固督汤治疗组小鼠脾脏中Th1、Th17和M-MDSC细胞百分比显著降低,G-MDSC细胞百分比升高(P<0.01),且消萎固督汤高剂量组这些变化更明显。相关性分析显示,Th1和Th17细胞与M-MDSC呈正相关,与G-MDSC呈负相关(P<0.01)。
消萎固督汤可通过提高G-MDSC细胞百分比、降低M-MDSC、Th1和Th17细胞百分比改善CIA小鼠关节炎症,且消萎固督汤高剂量组可产生与甲氨蝶呤相当的治疗效果,且安全性更好。