CXCL12/CXCR4在佐剂性关节炎大鼠脾脏中的表达及芍药苷-6′-O-苯磺酸酯的作用  

Paeoniflorin-6'-O-benzene sulfonate influences expression of CXCL12/CXCR4 in spleen of adjuvant-induced arthritis

作　　者：高梅 章敏 司敏 陈镜宇[1] 魏伟[1] GAO Mei;ZHANG Min;SI Min;CHEN Jing-yu;WEI Wei(Institute of Clinical Pharmacology of Anhui Medical University,Key Lab of Anti-inflammatory and Immune Medicine, Ministry of Education,Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine,Hefei 230032,China)

机构地区：[1]安徽医科大学临床药理研究所,抗炎免疫药理学教育部重点实验室,抗炎免疫药物安徽省协同创新中心,安徽合肥230032

出　　处：《中国药理学通报》2018年第5期639-644,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No81503084,81330081,31200675)

摘　　要：目的观察CXCL12及其受体CXCR4在佐剂性关节炎(adjuvant-induced arthritis,AA)大鼠脾脏中的表达,以及芍药苷-6'-O-苯磺酸酯(CP-25)对其的影响。方法完全弗氏佐剂(complete Freund’s adjuvant,CFA)诱导AA模型,随机分为正常对照组、模型组、CP-25(50 mg·kg^(-1))组和甲氨蝶呤(methotrexate,MTX,0.5 mg·kg^(-1))组。造模后d 14~28给药。HE染色观察脾脏的病理情况;免疫组化法和ELISA法检测脾脏中CXCL12的表达;免疫组化法和Western blot法检测脾脏CXCR4的表达。结果与正常对照组相比,AA大鼠脾脏动脉周围淋巴鞘的细胞密度增加,淋巴小结增多,脾脏中CXCL12和CXCR4表达增加;CP-25可以明显减少AA大鼠脾脏动脉周围淋巴鞘的细胞密度,改善淋巴小结增生,下调脾脏中CXCL12和CXCR4表达,且CXCL12和CXCR4表达与脾脏病理呈正相关。结论 AA大鼠脾脏CXCL12和CXCR4的高表达与脾脏病理改变有关,CP-25减少AA大鼠脾脏中CXCL12和CXCR4的表达可能是其发挥抗炎免疫调节作用的机制之一。Aim To observe the expression of CXCL12 and its receptor CXCR4 in spleen of rats with adjuvant-induced arthritis(AA)and the effects of paeoniflorin-6′-O-benzene sulfonate(CP-25).Methods AA rats were induced using complete Freund’s adjuvant and were randomly divided into normal group,AA group,CP-25 group(50 mg·kg-1)and methotrexate group(MTX,0.5 mg·kg-1),which were treated from d 14 to d 28.HE staining was used to assess the pathological changes of spleen.The expression of CXCL12 and CXCR4 in spleen was detected by ELISA,immunohistochemitry and Western blot.Results CP-25(50 mg·kg-1)alleviated the pathological changes of spleen and decreased the expression of CXCL12 and CXCR4 in spleen of AA rats.The pathological changes of spleen and the expression of CXCL12/CXCR4 in spleen revealed a positive correlation.Conclusions Increased expression of CXCL12 and its receptor CXCR4 may be associated with the pathological changes of spleen in AA rats,which plays an important role in the pathogenesis of RA.CP-25 has obvious therapeutic effect on AA rats and its mechanism may be related to the inhibition of the expression of CXCL12 and CXCR4 in the spleen.

关 键 词：佐剂性关节炎 脾脏 CXCL12 CXCR4 芍药苷-6′-O-苯磺酸酯 完全弗氏佐剂 

分 类 号：R-332[医药卫生] R284.1