首页|基于OPG/RANKL/RANK信号通路探讨桂枝芍药知母汤对胶原诱导性关节炎大鼠的影响

基于OPG/RANKL/RANK信号通路探讨桂枝芍药知母汤对胶原诱导性关节炎大鼠的影响

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目的 基于护骨因子(OPG)/NF-κB受体激活蛋白配体(RANKL)/NF-κB受体激活蛋白(RANK)信号通路探究桂枝芍药知母汤对胶原诱导性关节炎(CIA)大鼠骨破坏与骨保护相关因子的影响。方法 60只雌性Wistar大鼠按照体质量随机分为6组,正常组、模型组、雷公藤多苷组(0。01 g/kg)、桂枝芍药知母汤低剂量组(8。6 g/kg)、桂枝芍药知母汤中剂量组(17。2 g/kg)、桂枝芍药知母汤高剂量组(34。4 g/kg),每组10只。除正常组外,其他大鼠第1、8天使用牛Ⅱ型胶原蛋白(100 μg)复制CIA模型,在大鼠左足足底和尾根部位注射。造模成功后灌胃给药4周。监测大鼠一般状态、体质量及关节炎指数(AI)评分,酶联免疫吸附测定法检测大鼠血清中RANKL、OPG的含量,实时荧光PCR法与蛋白质印迹法分别测定踝关节中RANKL、RANK、OPG mRNA与蛋白表达水平。结果 与正常组比较,模型组一般状态欠佳,足趾肿胀明显,AI评分升高,血清RANKL含量升高、OPG含量降低,踝关节RANKL、RANK mRNA与蛋白表达均升高(均P<0。05)。与模型组比较,桂枝芍药知母汤各剂量组大鼠足趾肿胀程度与AI评分下降,血清RANKL含量降低、OPG含量升高,踝关节中RANKL、RANK mRNA与蛋白表达均降低,OPG mR-NA与蛋白表达均升高,踝关节RANKL/OPG值降低(均P<0。05)。结论 桂枝芍药知母汤能够改善CIA模型大鼠关节的骨破坏情况,其作用机制可能与降低RANKL水平、降低RANKL/OPG值、调控骨平衡有关。
Effect of Guizhi Shaoyao Zhimu Decoction on collagen-induced arthritis rat based on OPG/RANKL/RANK signaling pathway
Objective To study the effects of Guizhi Shaoyao Zhimu Decoction on factors related to bone destruction and bone protection in rats with collagen-induced arthritis(CIA)based on osteopro-tegerin(OPG)/receptor activator of NF-κB ligand(RANKL)/receptor activator of NF-κB(RANK)signaling pathway.Methods According to the body weight,60 female Wistar rats were randomly di-vided into the following six groups:the normal group,the model group,the Triperygium wilfordii mul-tiglucoside group(0.01 g/kg),the Guizhi Shaoyao Zhimu Decoction low-dose group(8.6 g/kg),the Guizhi Shaoyao Zhimu Decoction medium-dose group(17.2 g/kg),and the Guizhi Shaoyao Zhimu Decoction high-dose group(34.4 g/kg)(n=10 rats per group).The rats in all groups except for the normal group were given 100 μg bovine type Ⅱ collagen on the 1st and 8th days to establish the CIA model,and was injected into the left foot sole and tail root of the rats.After the successful modeling,the rats were treated by gavage for 4 weeks.The general state,body weight,and arthritis index(AI)score of rats were recorded,and the contents of RANKL and OPG in rat serum were determined by enzyme-linked immunosorbent assay.The mRNA and protein expressions of RANKL,RANK,and OPG in the ankle joint were determined through real-time PCR and Western blotting,respectively.Results Com-pared with the normal group,the general state of the model group was poor,the toe swelling was obvious,the AI score was increased,the serum RANKL content was increased,the serum OPG content was de-creased,and the mRNA and protein expressions of RANKL and RANK in the ankle joint were increased(P<0.05).Compared with the model group,the degree of toe swelling and the AI score of rats in the Guizhi Shaoyao Zhimu Decoction low-,medium-,and high-dose groups were decreased,the serum RANKL content was decreased,the serum OPG content was increased,the mRNA and protein expres-sions of RANKL and RANK in the ankle joint were decreased,the mRNA and protein expressions of OPG were increased,and the RANKL/OPG ratio of the ankle joint was decreased(P<0.05).Conclusion Guizhi Shaoyao Zhimu Decoction can improve the destruction of joint bone in CIA rats,and its mecha-nism of action may be related to reducing RANKL level,reducing RANKL/OPG ratio,and regulating bone balance.

Guizhi Shaoyao Zhimu DecoctionOPG/RANKL/RANK signaling pathwaycollagen-induced arthritisbone metabolismbone balancerats

杨双庆、马俊福、孟庆良、丁明辉、刘亚伟、张苏丹、王妍琦、李锦锦、李玉洁、冼锦忠

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河南中医药大学骨伤学院 郑州 450046

河南省中医院

西安市第五医院

桂枝芍药知母汤 护骨因子/NF-κB受体激活蛋白配体/NF-κB受体激活蛋白信号通路 胶原诱导性关节炎 骨代谢 骨平衡 大鼠

国家自然科学基金项目河南省中医药科学研究专项重大课题河南省中医药科学研究专项普通课题河南中医药大学2022年度研究生科研创新项目

8180405020-21ZYZD052022ZY10622022KYCX085

2024

北京中医药大学学报
北京中医药大学

北京中医药大学学报

CSTPCD北大核心
影响因子:1.568
ISSN:1006-2157
年,卷(期):2024.47(1)
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