1. 南方医科大学中西医结合医院
2. 南方医科大学中医药学院
纸质出版:2021
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[1]单文君,李长征,齐杰莹,谢丽芬,张巧莹,聂晓莉.小乌桂汤对胶原诱导性关节炎模型小鼠脾脏Th17/Treg平衡及血浆炎症因子的影响[J].中医杂志,2021,62(12):1065-1072.
SHAN Wenjun, LI Changzheng, QI Jieying, et al. Effects of Xiaowugui Decoction( 小乌桂汤) on Th17/Treg Balance in the Spleen and Inflammatory Factors in Plasma of Collagen-induced Arthritis Model Mice[J]. Journal of Traditional Chinese Medicine2021, 62(12): 1065-1072.
[1]单文君,李长征,齐杰莹,谢丽芬,张巧莹,聂晓莉.小乌桂汤对胶原诱导性关节炎模型小鼠脾脏Th17/Treg平衡及血浆炎症因子的影响[J].中医杂志,2021,62(12):1065-1072. DOI: 10.13288/j.11-2166/r.2021.12.011.
SHAN Wenjun, LI Changzheng, QI Jieying, et al. Effects of Xiaowugui Decoction( 小乌桂汤) on Th17/Treg Balance in the Spleen and Inflammatory Factors in Plasma of Collagen-induced Arthritis Model Mice[J]. Journal of Traditional Chinese Medicine2021, 62(12): 1065-1072. DOI: 10.13288/j.11-2166/r.2021.12.011.
目的探讨小乌桂汤治疗类风湿关节炎(RA)的作用机制。方法 60只雄性DBA/1小鼠随机分为正常组8只及造模组52只。造模组采用尾根部及背部分3点皮内注射鸡Ⅱ型胶原蛋白乳化液建立胶原诱导性关节炎(CIA)小鼠模型。造模成功的40只小鼠随机分成模型组、甲氨蝶呤组、小乌桂汤低剂量组、小乌桂汤中剂量组、小乌桂汤高剂量组
每组8只。甲氨蝶呤组予0.1mg/ml甲氨蝶呤药液2mg/kg灌胃
每周1次;小乌桂汤低、中、高剂量组分别予含生药19.5、39、75g/(kg·d)小乌桂汤灌胃
每日1次;正常组与模型组给予生理盐水0.2ml/10g灌胃
每日1次。4周后评定关节炎指数评分
测量发病足厚度
观察踝关节组织病理并进行组织病理学评分;检测脾脏辅助性T细胞17(Th17)、调节性T细胞(Treg)及血浆肿瘤坏死因子α(TNF-α)、白细胞介素6 (IL-6)、白细胞介素17(IL-17)、白细胞介素1β(IL-1β)、白细胞介素10(IL-10)的水平。结果与模型组比较
甲氨蝶呤组及小乌桂汤中、高剂量组关节炎指数评分
发病足厚度
脾脏Th17细胞水平
血浆TNF-α、IL-6、IL-17、IL-1β水平
关节病理总评分
血管翳及骨破坏评分均显著降低
Treg细胞水平均显著升高
甲氨蝶呤组及小乌桂汤高剂量组Th17/Treg值、滑膜炎评分显著降低(P<0.05或P<0.01)。与甲氨蝶呤组比较
小乌桂汤低剂量组脾脏Th17细胞水平、Th17/Treg值、关节病理总评分、血管翳及骨破坏评分显著升高
小乌桂汤低、中剂量组Treg细胞水平显著降低(P<0.01)。与小乌桂汤低剂量组比较
小乌桂汤中、高剂量组Th17细胞水平
Th17/Treg值显著降低
Treg细胞水平显著升高
小乌桂汤高剂量组病理总评分、血管翳评分显著降低(P<0.05或P<0.01)。与小乌桂汤中剂量组比较
小乌桂汤高剂量组Treg细胞水平显著升高(P<0.01)。结论小乌桂汤对CIA小鼠具有抗炎及免疫调节作用
以高剂量效果最佳
其作用机制与调节Th17/Treg的平衡
抑制TNF-α、IL-6、IL-17、IL-1β炎症因子的表达相关。
Objective To explore the mechanism of Xiaowugui Decoction(XWGD
小乌桂汤) for the treatment of rheumatoid arthritis. Methods Sixty male DBA/1 mice were randomly divided into normal group(n=8) and model group(n=52). To establish mice model of collagen-induced arthritis(CIA)
chicken type Ⅱ collagen emulsion was intracutaneously injected into the tail root and back of the mice at 3 points. Forty successful CIA model mice were randomly divided into model group
methotrexate group
XWGD low
medium
and high-dose groups
with 8 mice per group. The mice in methotrexate group were given 0.1 mg/ml methotrexate once a week
and the mice in XWGD low
medium and high-dose groups were respectively given 19.5
39
75 g/(kg·d) XWGD once a day. The mice in the normal group and model group were administered with 0.2 ml/10 g normal saline once a day. All the interventions were given by gavage for 4 weeks. The arthritis index score
thickness of the diseased paws and the histopathology of the ankle joint were evaluated. The ratio of helper T cell 17(Th17) and regulatory T cell(Treg) in spleens
and the expression levels of tumor necrosis factor-α(TNF-α)
interleukin-6(IL-6)
interleukin-17(IL-17)
interleukin-1β(IL-1β) and interleukin-10(IL-10) in plasma were detected. Results Compared to model group
the methotrexate group and XWGD medium and high-dose groups significantly decreased the arthritis index score
the thickness of the diseased paws
the ratio of Th17
the expression levels of plasma TNF-α
IL-6
IL-17
and IL-1β
the total ankle joint pathology score
and the pannus-bone destruction score
as well as increased the ratio of Treg; the methotrexate group and XWGD high-dose group significantly decreased the ratio of Th17/Treg and the synovitis score(P<0.05 or P<0.01). Compared to methotrexate group
XWGD low-dose group had significantly higher Th17 and Th17/Treg in spleen as well as higher total ankle joint pathology score and pannus-bone destruction score; the XWGD low and medium-dose groups had significantly lower ratio of Treg(P<0.05 or P<0.01). Compared to XWGD low-dose group
the Th17 and Th17/Treg ratio in the medium and high groups significantly reduced
Treg level increased; the total ankle joint pathology score and the pannus-bone destruction score in the high-dose group also significantly decreased(P<0.05 or P<0.01). The level of Treg in XWGD high-dose group was significantly higher than that of medium-dose group(P<0.01). Conclusion XWGD has anti-inflammatory and immune regulation effects on CIA model mice
and the high-dose works best. It may reduce the joint inflammation by regulating the balance of Th17/Treg and inhibiting the expression of TNF-α
IL-6
IL-17
and IL-1β.
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