摘要
目的观察丹皮酚对大鼠痛风性关节炎发展与NF-κB活化的影响及其机制。方法给予SD大鼠不同剂量的丹皮酚连续灌胃7 d。d 5向大鼠右踝关节腔内注射尿酸钠晶体。测量大鼠右足体积及步态评分;伊红-苏木素染色法进行关节组织学评分;抗酒石酸酸性磷酸酶染色法检测关节组织破骨细胞形成;免疫组织化学染色法检测肿瘤坏死因子(TNF)-α,白细胞介素(IL)-1β和IL-6表达;Western blot法检测关节组织中NF-κB p65蛋白和NF-κB抑制蛋白(IκB)α含量。结果丹皮酚明显减轻了MSU诱导的大鼠足肿胀、步态评分、组织学评分及破骨细胞形成。同时,丹皮酚明显降低了关节组织中TNF-α、IL-1β和IL-6的表达,增加了IκBα蛋白水平,但对p65蛋白表达没有明显影响。结论丹皮酚可明显抑制大鼠痛风性关节炎的发展,其机制与阻遏关节组织中的NF-κB活化,从而降低炎性介质表达密切相关。
Aim To investigate the effect of paeonol on the monosodium urate (MSU)-induced gouty arthritis (MGA) and nuclear factor (NF)-κB activation. Methods SD rats were treated intragastrically with paeonol for seven days. On day 5, MSU was injected intra-articularly in the ankle joints of rats. Paw volume and gait score was tested. Histological score was measured by hematoxylin and eosin staining. Osteoclast formation was measured by tartrate-resistant acid phosphatase staining. Expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 in articular tissues were analyzed by immunohistochemistry staining. Levels of NF-κB p65 and inhibitor of NF-κB(IκB)α were detected by Western blot. Results Paeonol markedly lowered the paw volume, gait score and histological score in MGA rats. Meanwhile, osteoclast formation and expressions of TNF-α, IL-1β and IL-6, which were enhanced in MGA rats, were markedly reduced by paeonol treatment. In addition, the depressed level of IκBα in MGA rats was enhanced significantly by paeonol treatment. However, the elevated level of p65 in MGA rats did not change markedly by paeonol treatment. Conclusions Paeonol attenuates the arthritic symptoms, joint structure damage and proinflammatory cytokine production through inhibiting the NF-κB activation in MGA rats.
作者
陈刚
殷钟意
郑旭煦
CHEN Gang;YIN Zhong-yi;ZHENG Xu-xu(Chongqing Key Lab of Nature Medicine Research,College of Environment and Resources,Chongqing Technology andBusiness University,Chongqing 400067,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2018年第12期1730-1735,共6页
Chinese Pharmacological Bulletin
基金
重庆市科委前沿与应用基础研究项目(No cstc2016jcyja0475)
重庆市教委科学技术研究项目(No KJ1400626)
关键词
丹皮酚
尿酸钠晶体
痛风性关节炎
核因子ΚB
炎性介质
破骨细胞
paeonol
monosodium urate crystals
gouty arthritis
nuclear factor-κB
proinflammatory cytokines
osteoclast