湖南中医药大学学报2023，Vol.43Issue(12)：2143-2149,7.DOI:10.3969/j.issn.1674-070X.2023.12.001
青藤碱配伍芍药苷协同增效抗胶原诱导性关节炎作用机制研究
Mechanism of action of sinomenine combined with paeoniflorin on collagen Ⅱ-induced arthritis
摘要
Abstract
Objective To investigate the therapeutic effects and mechanism of the combination of sinomenine(SIN)and paeoniflorin(PF)on collagen-induced arthritis(CIA).Methods Sixty female Wistar rats were randomized into normal,model,methotrexate(1 mg/kg),SIN(50 mg/kg),PF(120 mg/kg),and SIN(50 mg/kg)combined with PF(120 mg/kg)(SIN combined with PF group)groups,with 10 rats in each group.Except the normal group,the CIA model was established by multi-point injection of bovine collagen type Ⅱ/incomplete Freund adjuvant emulsion in the tail root skin of rats.The normal group and model group were orally administered distilled water,while the medication groups were orally administered corresponding drugs,continuously for 30 d.After modeling,the swelling volume of the hind paws,arthritis index score,and body weight of the rats were measured every 3 days.After treatment,CT scans were used to evaluate joint bone destruction in the rats,HE staining was used to observe pathological changes in the ankle joints;the serum content of tumor necrosis factor-alpha(TNF-α)and interleukin-1β(IL-1β)was measured by ELISA,and the expression levels of matrix metalloproteinase-2(MMP-2),matrix metalloproteinase-9(MMP-9),and tissue inhibitors of metalloproteinase-1(TIMP-1)in joint bone tissues were determined by Western blot.Results Compared with the normal group,the hind paw swelling volume and arthritis index score of model group was significantly higher(P<0.01),and the body weight was lower(P<0.01).The significant bone erosion in the toe joints with narrowing or even disappearance of the joint space was observed in the model group.While the levels of TNF-α and IL-1β in the serum and the protein expressions of MMP-2,MMP-9,and TIMP-1 in joint bone tissues all increased(P<0.01).Compared with model group,the swelling volume of hind paws and arthritic index score of rats in methotrexate,SIN,PF,and SIN combined with PF groups were lower(P<0.01),the body weight was higher(P<0.01),the degree of bone destruction significantly decreased,and the levels of TNF-α and IL-1β in serum and the protein expressions of MMP-2,MMP-9,and TIMP-1 in joint bone tissue decreased(P<0.01).Compared with SIN or PF group,the swelling volume of hind paws and arthritic index score of rats in SIN combined with PF group were lower(P<0.01),the body weight was higher(P<0.01),the degree of bone destruction decreased,and the levels of TNF-α and IL-1β in serum and the protein expressions of MMP-2,MMP-9,and TIMP-1 in joint bone tissue were lower(P<0.01).Conclusion SIN combined with PF has strong therapeutic effects on CIA,and the anti-arthritis effects are more obvious than SIN or PF alone to a certain extent.The mechanism may be related to inhibiting the expressions of TNF-α and IL-1β,lowering expressions of MMP-2 and MMP-9 in joint bone tissue,and promoting the expression of TIMP-1.关键词
青藤碱/芍药苷/配伍用药/胶原诱导性关节炎/细胞因子/基质金属蛋白酶Key words
sinomenine/paeoniflorin/combination of medication/collagen Ⅱ-induced arthritis/cytokines/matrix metallo-proteinase分类
医药卫生引用本文复制引用
戴宗顺,张逢,林也,黄红,李鑫,彭清华,蔡雄..青藤碱配伍芍药苷协同增效抗胶原诱导性关节炎作用机制研究[J].湖南中医药大学学报,2023,43(12):2143-2149,7.基金项目
国家自然科学基金面上项目(82274506,81373540) （82274506,81373540）
中国博士后科学基金面上项目(2022M721128) （2022M721128）
湖南省自然科学基金项目(2023JJ30455,2023JJ40477) （2023JJ30455,2023JJ40477）
湖南省教育厅科学基金一般项目(22C0197) （22C0197）
长沙市自然科学基金项目(kq2208499) （kq2208499）
湖南中医药大学校级科研基金项目(2021XJJJ007) （2021XJJJ007）
湖南中医药大学院校联合课题重点项目(2022XYLH158). （2022XYLH158）
