文献类型：期刊文献

中文题名：秦艽与威灵仙组分配伍对类风湿关节炎大鼠的治疗作用

英文题名：Therapeutic effects of the compounded components of Gentianae Macrophyllae Radix and Clematidis Radix et Rhizoma on rats with rheumatoid arthritis

作者：郭从嘉[1];吴国泰[1,2];高慧琴[1,2];郑丽霞[1];李飒[1];王丽明[1];郝倩莹[1]

第一作者：郭从嘉

机构：[1]甘肃中医药大学药学院,甘肃兰州730101;[2]甘肃省中药药理与毒理学重点实验室,甘肃兰州730101

第一机构：甘肃中医药大学药学院（西北中藏药协同创新中心办公室）

年份：2023

卷号：39

期号：21

起止页码：3139

中文期刊名：中国临床药理学杂志

外文期刊名：The Chinese Journal of Clinical Pharmacology

收录：CSTPCD;;北大核心:【北大核心2020】；CSCD:【CSCD2023_2024】；

基金：国家自然科学基金地区基金资助项目(81960725)。

语种：中文

中文关键词：秦艽;威灵仙;组分配伍;类风湿关节炎;B淋巴细胞瘤-2;转录激活蛋白-1

外文关键词：Gentianae Macrophyllae Radix;Clematidis Radix et Rhizoma;component combination;rheumatoid arthritis;B-cell lymphocytoma-2;activator protein-1

摘要：目的观察秦艽与威灵仙组分配伍对类风湿关节炎(RA)模型大鼠的治疗作用,探索作用机制。方法采用Ⅱ型胶原复制关节炎(CIA)大鼠模型,造模成功大鼠用随机数表法分为模型组、甲氨蝶呤组(0.38 mg·kg^(-1)甲氨蝶呤)、木龙组(5.06 mg·kg^(-1)木兰花碱+150.45 mg·kg^(-1)龙胆苦苷)、木獐组(5.06 mg·kg^(-1)木兰花碱+3.46 mg·kg^(-1)獐牙菜苷)、木獐苦组(5.06 mg·kg^(-1)木兰花碱+9.30 mg·kg^(-1)獐牙菜苦苷)、灵龙组(16.43 mg·kg^(-1)灵仙新苷+150.45 mg·kg^(-1)龙胆苦苷)、灵獐组(16.43 mg·kg^(-1)灵仙新苷+3.46 mg·kg^(-1)獐牙菜苷)、灵獐苦组(16.43 mg·kg^(-1)灵仙新苷+9.30 mg·kg^(-1)獐牙菜苦苷),另设正常组,每组8只,灌胃给药,每天1次,连续15 d。观察大鼠足跖肿胀度、关节炎指数(AI);以免疫组化法测定大鼠踝关节AP-1蛋白表达水平;以实时荧光定量聚合酶链反应法测定大鼠踝关节AP-1 mRNA表达水平。结果模型组、甲氨蝶呤组、木龙组、木獐组、木獐苦组、灵龙组、灵獐组、灵獐苦组大鼠足跖肿胀度分别为0.78±0.10、0.55±0.10、0.53±0.10、0.63±0.08、0.58±0.13、0.56±0.12、0.61±0.11和0.60±0.10;关节炎指数分别为3.13±0.17、2.08±0.39、2.25±0.30、2.38±0.42、2.25±0.46、2.46±0.40、2.33±0.47和2.13±0.35;甲氨蝶呤组、灵獐苦组上述指标与模型组比较,差异均有统计学意义(P<0.01,P<0.05)。正常组、模型组、甲氨蝶呤组及各配伍组大鼠踝关节AP-1蛋白水平分别为0.10±0.01、0.28±0.02、0.12±0.01、0.23±0.03、0.19±0.02、0.15±0.01、0.17±0.02、0.15±0.01和0.12±0.01;AP-1 mRNA分别为1.00±0.02、2.92±0.03、1.11±0.02、2.12±0.04、2.43±0.04、1.34±0.02、1.55±0.04、1.70±0.04、1.18±0.03;与模型组比较,除木龙组大鼠踝关节AP-1蛋白表达水平外,各配伍组AP-1蛋白和mRNA均显著降低(均P<0.01)。结论秦艽与威灵仙组分配伍对RA模型大鼠具有治疗作用,其机制与降低血清Bcl-2水平及抑制AP-1异常表达有关。
Objective To observe the therapeutic effects of the combination of Gentianae Macrophyllae Radix and Clematidis Radix et Rhizoma(GMR+CRR)on rheumatoid arthritis(RA)rats and explore the mechanism of effects.Methods TypeⅡcollagen was used to induce replication of the collagen-induced arthritis rat model(CIA)in SD rats,and the model rats were divided into model group,methotrexate(MTX)group(0.38 mg·kg^(-1)),magnoflorine(MAG)+gentiopicroside(G PS)group(5.06+150.45 mg·kg^(-1)),MAG+sweroside(SWS)group(5.06+3.46 mg·kg^(-1)),MAG+swertiamarin(SWT)group(5.06+9.30 mg·kg^(-1)),clematichinenoside AR(CAR)+GPS group(16.43+150.45 mg·kg^(-1)),CAR+SWS group(16.43+3.46 mg·kg^(-1)),CAR+SWT group(16.43+9.30 mg·kg^(-1)),additionally setting a normal group,8 rats in each group,the medication was administered by gavage once a day for 15 consecutive days.During the experiment,the andarthritis index(AI)scores of the foot and plantar swelling of rats were observed and recorded;the protein expression of AP-1 in rats’ankle joints was detected by immunohistochemistry,and the expression of AP-1 mRNA in ankle joint of rats was detected by Real-time fluorescence quantitative polymerase chain reaction.Results The swelling of foot and plantar in the model group,MTX group and group with each component administered in combination were 0.78±0.10,0.55±0.10,0.53±0.10,0.63±0.08,0.58±0.13,0.56±0.12,0.61±0.11 and 0.60±0.10;the order of arthritis indices were 3.13±0.17,2.08±0.39,2.25±0.30,2.38±0.42,2.25±0.46,2.46±0.40,2.33±0.47 and 2.13±0.35.Compared with the model group,the swelling degree,AI and erythrocyte sedimentation rate of rats’feet in the MTX group and CAR+SWS group were significantly reduced(P<0.01,P<0.05).The AP-1 protein levels in the ankle joint of rats in the normal group,model group,MTX group,and each combination group were 0.10±0.01,0.28±0.02,0.12±0.01,0.23±0.03,0.19±0.02,0.15±0.01,0.17±0.02,0.15±0.01 and 0.12±0.01,respectively;the AP-1 mRNA levels were 1.00±0.02,2.92±0.03,1.11±0.02,2.12±0.04,2.43±0.04,1.34±0.02,1.55±0.04,1.70±0.04 and 1.18±0.03.Compared with the model group,except for the expression level of AP-1 protein in the ankle joint of rats in MAG+GPS,the AP-1 protein and AP-1 mRNA in each combination group were significantly reduced(P<0.01).Conclusion The combination of Gentianae Macrophyllae Radix and Clematidis Radix et Rhizoma has a therapeutic effect on RA rats,and the mechanism is related to the reduction of serum Bcl-2 level and inhibition of abnormal expression of AP-1.