千斤拔多糖对类风湿关节炎模型小鼠干预效果研究

doi:10.5246/jcps.2024.08.052

中国药学(英文版) ›› 2024, Vol. 33 ›› Issue (8): 705-713.DOI: 10.5246/jcps.2024.08.052

千斤拔多糖对类风湿关节炎模型小鼠干预效果研究

张楠¹^,^#, 刘志敏¹^,^#, 杨宣梅¹, 李爽¹, 高艺文¹^,^*(), 秦海洸²^,^*()

^1. 滨州医学院烟台附属医院, 山东烟台 264100
^2. 山东中医药高等专科学校, 山东烟台 264100

收稿日期:2023-10-24 修回日期:2023-11-21 接受日期:2023-12-31 出版日期:2024-08-30 发布日期:2024-08-30
通讯作者: 高艺文, 秦海洸

Assessing the therapeutic impact of Qianjinba polysaccharide in a rheumatoid arthritis murine model

Nan Zhang¹^,^#, Zhimin Liu¹^,^#, Xuanmei Yang¹, Shuang Li¹, Yiwen Gao¹^,^*(), Haiguang Qin²^,^*()

¹ Yantai?Affiliated?Hospital?of?Binzhou?Medical?College,?Yantai?264100,?Shandong, China
² Shandong College of Traditional Chinese Medicine, Yantai?264100,?Shandong, China

Received:2023-10-24 Revised:2023-11-21 Accepted:2023-12-31 Online:2024-08-30 Published:2024-08-30
Contact: Yiwen Gao, Haiguang Qin
About author:
^# Nan Zhang and Zhimin Liu contributed equally to this work.
Supported by:
Shandong Provincial Key Project of TCM Science and Technology (Grant No. 2021Z051), Shandong Medical and Health Science and Technology Development Program (Grant No. 202102040972) and supported by Binzhou Medical College Student Innovation and Entrepreneurship Training Program (Grant No. X202210440354).

摘要/Abstract

摘要：

千斤拔主产于我国南方, 被广泛应用于风湿痹痛、妇科等类型的中成药生产, 被国家列为中药保护品种。本研究目的在于探讨千斤拔多糖(QJBDT)抗类风湿关节炎的疗效, 初步研究其抑制小鼠类风湿关节炎的作用机制。将昆明小鼠(KM)随机分为正常组, 模型组(LPS组), 千斤拔多糖低、中、高剂量组(QJBDT低、中、高组), 阳性对照组(TGP组), 每组10只。注射Ⅱ型胶原蛋白于右后足关节处致炎造模, 造模7天后给予不同浓度千斤拔多糖和阳性药白芍总苷灌胃, 每天给药1次, 连续21天。每周称重同时评估记录大鼠体质量、测定足肿胀度、关节炎指数评分; 对关节组织进行病理观察; 检测右足关节组织蛋白小鼠p38丝裂原活化蛋白激酶信号通路与核因子NF-κB的蛋白表达情况; ELISA试剂盒检测小鼠血清中白细胞介素-β (IL-β)、白细胞介素-17 (IL-17)、肿瘤坏死因子-α (TNF-α)的表达情况。结果发现千斤拔多糖可以有效降低胶原诱导的关节炎小鼠足肿胀度、关节炎指数, 改善小鼠体重降低(P < 0.05); 减轻小鼠关节病理损伤; 同时下调转录因子p38、NF-κB的蛋白表达(P < 0.05); 降低小鼠血清中炎症因子IL-β、IL-17、TNF-α的含量(P < 0.05)。本研究发现千斤拔多糖对小鼠类风湿关节炎有较好的治疗效果, 抑制转录因子p38及NF-κB表达, 减少炎症因子的产生, 在一定程度上缓解类风湿关节炎的进展。

关键词: 千斤拔多糖, 类风湿关节炎, 炎症因子, p38丝裂原活化蛋白激酶信号通路, NF-κB

Abstract:

Qianjinba is primarily cultivated in the southern regions of China and finds extensive use in traditional Chinese medicine (TCM) for conditions such as rheumatism, arthralgia, and gynecological ailments. It has been officially recognized as a protected variety of TCM by the state. The aim of this study was to investigate the therapeutic potential of Qianjinba polysaccharide (QJBDT) in treating rheumatoid arthritis (RA) in mice, along with a preliminary exploration of its mechanisms for inhibiting RA in these animals. Kunming mice (KM) were randomly divided into several groups, including a normal group, a model group (LPS group), low-dose, medium-dose, and high-dose QJBDT groups, as well as a positive control group (TGP group), each consisting of 10 mice. To induce inflammation and create an RA model, type II collagen was injected into the right hind foot joint. Following a 7-day modeling period, various concentrations of QJBDT and the positive control drug total glycoside of peony were administered via gavage once a day for 21 consecutive days. Throughout the study, we monitored and recorded the mice's weight, measured foot swelling, and assessed the arthritis index on a weekly basis. We also conducted pathological examinations of joint tissues and analyzed the signal pathway of p38 mitogen-activated protein kinase (MAPK) as well as the protein expression of nuclear factor NF-κB in the mice’s right foot joint tissues. Additionally, we employed ELISA to detect the levels of interleukin-β (IL-β), IL-17, and tumor necrosis factor-α (TNF-α) in the mice’s serum. The results of this study revealed that QJBDT effectively reduced the degree of foot swelling and the arthritis index in collagen-induced arthritis mice while improving their weight loss (P < 0.05). Furthermore, it alleviated the pathological damage observed in the mice’s joints. Notably, the expression of transcription factors p38 and NF-κB proteins was down-regulated (P < 0.05), and the levels of inflammatory cytokines IL-β, IL-17, and TNF-α in the mice’s serum were decreased (P < 0.05). In conclusion, this study demonstrated that polysaccharides could inhibit the expression of transcription factors p38 and NF-κB, reduce the production of inflammatory factors, and alleviate the progression of RA to a certain extent.

Key words: Qianjinba polysaccharide, Rheumatoid arthritis, Inflammatory factors, p38 Mitogen activated protein kinase signaling pathway, NF-κB

Supporting:

张楠, 刘志敏, 杨宣梅, 李爽, 高艺文, 秦海洸. 千斤拔多糖对类风湿关节炎模型小鼠干预效果研究[J]. 中国药学(英文版), 2024, 33(8): 705-713.

Nan Zhang, Zhimin Liu, Xuanmei Yang, Shuang Li, Yiwen Gao, Haiguang Qin. Assessing the therapeutic impact of Qianjinba polysaccharide in a rheumatoid arthritis murine model[J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(8): 705-713.

图/表 7

Table 1. Effect of different body weights of mice (x ± s, n = 10).

Table 2. Effect of QJBDT on paw edema in mice (x ± s, n = 10).

Table 3. Effect of QJBDT on AI score in mice (x ± s, n = 10).

Figure 1. Effect of different concentrations of QJBDT on mouse joint bone tissue. (a) Effects of polysaccharide from Herba Physalis on the joints of mice; (b) Effects of polysaccharide from Herba Physalis on the histopathology of joints of mice (H&E, ×200).

Figure 2. Effect of different concentrations of QJBDT on p38 and NF-κB protein expression. A. Normal; B. Model; C. QJBDT (200 μg/mL); D. QJBDT (600 μg/mL); E. QJBDT (1000 μg/mL); F. TGP.

Table 4. Comparison of the gray value of p38 and NF-κB proteins (x ± s, n = 10).

Table 5. Effect of different concentrations on IL-1β, IL-17, and TNF-α expression (x ± s, n = 10).

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千斤拔多糖对类风湿关节炎模型小鼠干预效果研究

Assessing the therapeutic impact of Qianjinba polysaccharide in a rheumatoid arthritis murine model

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