
浏览全部资源
扫码关注微信
1.中国中医科学院 中医基础理论研究所,北京 100700
2.首都医科大学 附属北京地坛医院 传染病研究所,北京 100015
3.首都医科大学 附属北京世纪坛医院,北京 100038
揭珊珊,在读硕士,从事中西医结合基础研究,E-mail:jss010210@163.com
马雅銮,博士,研究员,从事中医药抗炎与免疫药理研究,E-mail:yaluanma@163.com
收稿日期:2022-03-10,
网络出版日期:2022-05-07,
纸质出版日期:2022-07-05
移动端阅览
揭珊珊,孙慧娟,刘建鑫等.黄连解毒汤调控炎性免疫抗类风湿性关节炎机制[J].中国实验方剂学杂志,2022,28(13):28-33.
JIE Shanshan,SUN Huijuan,LIU Jianxin,et al.Huanglian Jiedutang Regulates Inflammatory Immunity to Relieve Rheumatoid Arthritis[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(13):28-33.
揭珊珊,孙慧娟,刘建鑫等.黄连解毒汤调控炎性免疫抗类风湿性关节炎机制[J].中国实验方剂学杂志,2022,28(13):28-33. DOI: 10.13422/j.cnki.syfjx.20221336.
JIE Shanshan,SUN Huijuan,LIU Jianxin,et al.Huanglian Jiedutang Regulates Inflammatory Immunity to Relieve Rheumatoid Arthritis[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(13):28-33. DOI: 10.13422/j.cnki.syfjx.20221336.
目的
2
观察黄连解毒汤对胶原诱导性关节炎(CIA)模型小鼠病理改变及免疫损伤的影响,探讨黄连解毒汤抗类风湿性关节炎的可能机制。
方法
2
24只DBA/1小鼠,随机分为正常组、模型组、甲氨喋呤组和黄连解毒汤组,每组6只,采用Ⅱ型胶原诱导建立CIA小鼠模型,给药组给予黄连解毒汤水煎液(5 g·kg
-1
)和甲氨喋呤(0.5 mg·kg
-1
)干预,观察小鼠关节肿胀症状,每3 d进行关节炎指数评分,评分达到峰值后取材;流式细胞仪检测外周血粒细胞、单核细胞、T淋巴细胞;实时荧光定量聚合酶链式反应(Real-time PCR)检测关节炎症因子表达;微计算机断层扫描技术(Micro-CT)扫描踝关节;苏木素-伊红(HE)染色检测关节组织病理改变。
结果
2
与正常组比较,模型组小鼠关节肿胀,关节炎指数评分明显升高(
P
<
0.05);外周血粒细胞比例明显升高(
P
<
0.05),单核细胞、T淋巴细胞比例明显降低(
P
<
0.05),中性粒细胞淋巴细胞比例(NLR)显著升高(
P
<
0.01);关节组织炎症因子肿瘤坏死因子-
α
(TNF-
α
)、白细胞介素(IL)-1
β
、IL-6表达升高(
P
<
0.01);Micro-CT可见踝关节明显骨质破坏,病理可见到关节周围组织存在大量的炎性细胞浸润、滑膜增生。与模型组比较,黄连解毒汤组小鼠关节肿胀症状明显减轻,关节炎指数评分明显降低(
P
<
0.05);外周血T淋巴细胞比例升高,NLR显著降低(
P
<
0.01);关节中炎症因子TNF-
α
、IL-1
β
、IL-6的表达显著下降(
P
<
0.01);骨破坏及关节组织病理损伤情况明显改善。
结论
2
Ⅱ型胶原导致CIA小鼠全身和关节局部炎性免疫损伤,黄连解毒汤干预减轻炎性免疫损伤,并且对关节局部的作用更为显著,从而抑制CIA小鼠关节病变和骨破坏。
Objective
2
To observe the effects of Huanglian Jiedutang on pathological and immune damage in collagen-induced arthritis (CIA) model mice, and to explore the possible mechanism of Huanglian Jiedutang in relieving rheumatoid arthritis.
Method
2
Twenty-four DBA/1 mice were randomly divided into normal group, model group, methotrexate group and Huanglian Jiedutang group, with six mice in each group. The CIA mice model were established using type Ⅱ collagen induction. The administration groups were respectively treated with Huanglian Jiedutang (5 g·kg
-1
) and methotrexate (0.5 mg·kg
-1
). The joint swelling symptoms of the mice were observed, and the arthritis index was scored every 3 days. Flow cytometry was employed to detect granulocytes, monocytes, and T lymphocytes in peripheral blood. The expression of inflammatory cytokines in joint was determined by real-time polymerase chain reaction (Real-time PCR). The ankle joint was scanned by micro-computed tomography (Micro-CT), and the histopathological changes were observed through hematoxylin-eosin (HE) staining.
Result
2
Compared with the normal group, the modeling led to joint swelling, elevated the joint index score (
P
<
0.05), increased the proportion of granulocytes (
P
<
0.05) and decreased that of monocytes and T lymphocytes (
P
<
0.01) in peripheral blood, and raised the neutrophil-to-lymphocyte ratio (NLR) (
P
<
0.01). Further, it up-regulated the expression of inflammatory cytokines such as tumor necrosis factor-
α
(TNF-
α
), interleukin (IL)-1
β
, and IL-6 in joint (
P
<
0.01). Micro-CT showed obvious bone destruction in the ankle joint, and pathological examination revealed the infiltration of a large number of inflammatory cells and the synovial hyperplasia of joint tissue. Compared with the model group, Huanglian Jiedutang alleviated the symptoms of joint swelling, lowered the score of arthritis index (
P
<
0.05), increased the proportion of T lymphocytes and lowered NLR (
P
<
0.01). Moreover, it down-regulated the expression levels of TNF-
α
, IL-1
β
, and IL-6 in joint (
P
<
0.01) and alleviated the bone destruction and pathological injury of joint tissue.
Conclusion
2
Type Ⅱ collagen caused systemic and local inflammatory immune damage in CIA mice. Huanglian Jiedutang alleviates such injury, especially for that in local joint, thereby inhibiting joint injury and bone destruction in CIA mice.
JUTLEY G , RAZA K , BUCKLEY C D . New pathogenic insights into rheumatoid arthritis [J]. Curr Opin Rheumatol , 2015 , 27 ( 3 ): 249 - 255 .
WRIGHT H L , MOOTS R J , EDWARDS S W . The multifactorial role of neutrophils in rheumatoid arthritis [J]. Nat Rev Rheumatol , 2014 , 10 ( 10 ): 593 - 601 .
董颖 , 刘保光 , 许二平 . 黄连解毒汤抗炎作用与临床应用研究进展 [J]. 中国实验方剂学杂志 , 2021 , 27 ( 12 ): 245 - 250 .
郭璐露 . 黄连解毒汤联合来氟米特治疗类风湿性关节炎41例临床观察 [J]. 湖南中医杂志 , 2020 , 36 ( 1 ): 30 - 32 .
刘忠第 , 姜淼 , 谭勇 , 等 . 类风湿关节炎寒热方证对应的网络药理学研究策略 [J]. 中华中医药杂志 , 2015 , 30 ( 9 ): 3191 - 3195 .
孙慧娟 , 朱镠娈 , 李蕊 . 黄连解毒汤含药血清调控中性粒细胞功能的实验研究 [J]. 中国中西医结合杂志 , 2021 , 41 ( 2 ): 212 - 217 .
李彤 , 韩俊燕 , 王蓓蓓 , 等 . 黄连解毒汤调控单核、巨噬细胞及泡沫细胞分化的实验研究 [J]. 中国中西医结合杂志 , 2014 , 34 ( 9 ): 1096 - 1102 .
陈冰 , 孔雅娴 , 李玉梅 , 等 . 黄连解毒汤对ApoE基因敲除小鼠单核细胞发育的影响 [J]. 中国中西医结合杂志 , 2016 , 36 ( 1 ): 99 - 103 .
马雅銮 , 李彤 , 王蓓蓓 , 等 . 黄连解毒汤对高脂血症小鼠肝脏保护作用的观察 [J]. 中国中西医结合杂志 , 2013 , 33 ( 8 ): 1107 - 1111 .
马雅銮 , 王蓓蓓 , 韩俊燕 , 等 . 黄连解毒汤对高脂饮食ApoE -/- 小鼠全身和主动脉血管局部免疫反应影响的研究 [J]. 中国中西医结合杂志 , 2013 , 33 ( 11 ): 1520 - 1525 .
张玲玲 , 刘云洁 , 童彤 , 等 . DBA/1小鼠胶原性关节炎模型建立方法及评价指标 [J]. 中国药理学通报 , 2010 , 26 ( 8 ): 1108 - 1111 .
杨亚旭 , 邵丽娟 , 黄小丽 , 等 . 类风湿关节炎常用动物造模方法的研究进展及评价标准比较 [J]. 风湿病与关节炎 , 2015 , 4 ( 4 ): 62 - 66 .
袁蓓 , 苏晓慧 , 郭婉怡 , 等 . 瘀血痹片对大鼠胶原诱导性关节炎的干预作用及抗炎机制 [J]. 中国实验方剂学杂志 , 2021 , 27 ( 11 ): 52 - 62 .
刘立玲 , 田雅格 , 苏晓慧 , 等 . 雷公藤多苷片和雷公藤片对CIA模型大鼠干预的量毒效比较研究 [J]. 中国中药杂志 , 2019 , 44 ( 16 ): 3502 - 3511 .
ERRE G L , PALIOGIANNIS P , CASTAGNA F , et al . Meta-analysis of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio in rheumatoid arthritis [J]. Eur J Clin Invest , 2019 , 49 ( 1 ): e13037 .
王鑫 , 周彩云 , 马芳 , 等 . 房定亚运用专方治疗风湿病经验 [J]. 上海中医药杂志 , 2012 , 46 ( 3 ): 1 - 3 .
CROIA C , BURSI R , SUTERA D , et al . One year in review 2019:Pathogenesis of rheumatoid arthritis [J]. Clin Exp Rheumatol , 2019 , 37 ( 3 ): 347 - 357 .
RHYS H I , DELL ACCIO F , PITZALIS C , et al . Neutrophil microvesicles from healthy control and rheumatoid arthritis patients prevent the inflammatory activation of macrophages [J]. EBioMedicine , 2018 , 29 : 60 - 69 .
CIZ M , DENEV P , KRATCHANOVA M , et al . Flavonoids inhibit the respiratory burst of neutrophils in mammals [J]. Oxid Med Cell Longev , 2012 , doi: 10.1155/2012/181295 http://dx.doi.org/10.1155/2012/181295 .
MITTAL M , SIDDIQUI M R , TRAN K , et al . Reactive oxygen species in inflammation and tissue injury [J]. Antioxid Redox Sign , 2014 , 20 ( 7 ): 1126 - 1167 .
王克军 . 类风湿关节炎患者外周血CD4 T细胞关节局部趋化机制 [J]. 中国老年学杂志 , 2015 , 35 ( 18 ): 5259 - 5261 .
YANY S , ZHANG X , CHEN J , et al . Induced,but not natural,regulatory T cells retain phenotype and function following exposure to inflamed synovial fibroblasts [J]. Sci Adv , 2020 , 6 ( 44 ): eabb0606 .
TESTA D , CALVACCHI S , PETRELLI F , et al . One year in review 2021:Pathogenesis of rheumatoid arthritis [J]. Clin Exp Rheumatol , 2021 , 39 ( 3 ): 445 - 452 .
杨林 , 吕丹 , 沈小芳 , 等 . 细胞因子对类风湿性关节炎骨平衡的调节作用 [J]. 生命科学 , 2019 , 31 ( 1 ): 35 - 43 .
李利青 , 张逢 , 彭馥芝 , 等 . 类风湿关节炎实验性动物模型研究进展 [J]. 中国药理学通报 , 2021 , 37 ( 11 ): 1492 - 1497 .
谢小倩 , 万志杰 , 武小晗 , 等 . 类风湿性关节炎实验动物模型研究进展 [J]. 世界最新医学信息文摘 , 2019 , 19 ( 80 ): 118 - 119 .
0
浏览量
44
下载量
6
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621