Page 60 - 《中国药房》2022年16期

青风藤配伍制附子对RA模型大鼠骨破坏的干预作用及机制 Δ

2
1
1
韩远山 ，易刚强 ，李 鑫 ，欧阳琳 ，蔡嘉洛 ，邹蔓姝（1.湖南中医药大学第一附属医院科研部，长沙
1＊
2
2 #
410007；2.湖南中医药大学药学院，长沙 410208）
中图分类号 R965 文献标志码 A 文章编号 1001-0408（2022）16-1974-06
DOI 10.6039/j.issn.1001-0408.2022.16.10
摘 要 目的 评价青风藤配伍制附子对类风湿性关节炎（RA）模型大鼠骨破坏的干预作用，并探讨其作用机制。方法 将40只SD
大鼠按体质量随机分成空白组、模型组、阳性对照组（吲哚美辛0.013 5 g/kg）、青风藤配伍制附子组（青风藤1.08 g/kg+制附子1.35
g/kg），每组10只。除空白组外，其余各组大鼠均通过注射牛Ⅱ型胶原复制RA模型。各组大鼠连续灌胃相应药物或蒸馏水，记录
一般情况、体质量、足肿胀度及关节炎症指数（AI）评分。第30天给药结束后，采用小动物CT机检测大鼠踝关节骨质变化；采用酶
联免疫吸附测定法检测血清中炎症因子[白细胞介素31（IL-31）、IL-25、IL-3]与趋化因子[核因子κB受体激活蛋白配体（RANKL）、
核因子κB受体激活蛋白（RANK）、护骨因子（OPG）]的水平；采用HE染色法观察大鼠踝关节病理学情况；采用免疫组织化学法检
测大鼠踝关节滑膜组织中RANKL、RANK、OPG的表达情况。结果 与空白组比较，第12～30天模型组大鼠精神状态虚弱，活动力
下降明显，毛发失去光泽，体质量显著降低（P＜0.05 或 P＜0.01）；第 12～30 天模型组大鼠足肿胀度显著增加、AI 评分显著升高
（P＜0.01）；踝关节表面粗糙，组织破坏明显、骨侵蚀严重；血清中IL-31、IL-25、IL-3、RANKL、RANK水平显著升高，OPG水平显著
下降（P＜0.01）；踝关节滑膜组织中RANKL、RANK的光密度显著升高，OPG的光密度显著下降（P＜0.01）。与模型组比较，各给
药组上述指标均有不同程度改善，大部分差异具有统计学意义（P＜0.05 或 P＜0.01）。结论 青风藤配伍制附子能通过抑制
RANKL/RANK/OPG通路，从而抑制破骨细胞过度增殖，恢复骨代谢平衡，进而起到保护骨关节、治疗RA的作用。
关键词 类风湿性关节炎；青风藤；制附子；配伍

Intervention effect and mechanism of Caulis sinomenii compatible with prepared Aconiti Lateralis on bone
destruction in RA model rats
2
2
1
1
2
HAN Yuanshan ，YI Gangqiang ，LI Xin ，OUYANG Lin ，CAI Jialuo ，ZOU Manshu（1. Dept. of Scientific
1
Research，the First Affiliated Hospital of Hunan University of Chinese Medicine，Changsha 410007，China；
2. College of Pharmacy，Hunan University of Chinese Medicine，Changsha 410208，China）
ABSTRACT OBJECTIVE To evaluate the intervention effect of Caulis sinomenii compatible with prepared Aconiti Lateralis on
bone destruction in rheumatoid arthritis（RA）model rats，and to investigate its mechanism. METHODS Totally 40 SD rats were
randomly divided into blank group，model group，positive control group（indomethacin 0.013 5 g/kg）and C. sinomenii compatible
with prepared Aconiti Lateralis group（C. sinomenii 1.08 g/kg+prepared Aconiti Lateralis 1.35 g/kg）according to body mass，with
10 rats in each group. Except for the blank group，all the other groups made RA rat models by injecting type Ⅱ bovine collagen.
Rats in each group were given corresponding drugs or distilled water intragastrically. The general information，body weight，foot
swelling and arthritis index（AI）scores of rats in each group were recorded. After the 30th day of administration，the changes of
ankle bone in rats were detected by small animal CT machine. The levels of inflammatory factors [interleukin-31（IL-31），IL-25
and IL-3] and chemokines [receptor activator of nuclear factor κ B ligand（RANKL），receptor activator of nuclear factor κ B
（RANK）and osteoprotegerin（OPG）] in serum were detected by enzyme-linked immunosorbent assay. Pathological indexes of rat
ankle joint were observed by HE staining. Immunohistochemical method was used to detect the expression of RANKL，RANK and
OPG in synovial tissue of rat ankle joint. RESULTS Compared with blank group，the mental state of the model group was weak，
the activity decreased significantly，the hair lost luster，and the body weight decreased significantly on the 12th to 30th days（P＜
0.05 or P＜0.01）；the swelling degree of the foot was significantly increased and the AI score was significantly increased on the
12th to 30th days（P＜0.01）；the ankle joint in model group had rough surface，obvious tissue damage and serious bone erosion；
serum levels of IL-31，IL-25，IL-3，RANKL and RANK were increased significantly，while the level of OPG was decreased
significantly （P＜0.01）； the expression of RANKL and
Δ 基金项目 湖南省中医药科研计划项目（No.201602）；长沙市自
RANK in synovium of ankle joint increased significantly，
然科学基金资助项目（No.kq2007040）
＊第一作者 助理研究员，硕士。研究方向：中医药防治重大疾 while the expression of OPG decreased significantly （P＜
病。E-mail：1217983755@qq.com 0.01）. Compared with model group，the above indexes of
# 通信作者 高级政工师，硕士。研究方向：中药神经药理学。 administration groups were improved to varying degrees，and
E-mail：Ygq8228@163.com most of the differences were statistically significant（P＜0.05

·1974 · China Pharmacy 2022 Vol. 33 No. 16 中国药房 2022年第33卷第16期