芍药苷对胶原性关节炎大鼠滑膜细胞G蛋白偶联信号的调节作用  

Regulatory effects of Paeoniflorin on G protein-coupled signaling of synoviocytes in collagen-induced arthritis rats

作　　者：张玲玲[1] 魏伟[1] 汪庆童[1] 陈镜宇[1] 陈尹[1] 吴华勋[1] 

机构地区：[1]安徽医科大学临床药理研究所,安徽省高校省级抗炎免疫药理学重点实验室,安徽省高校抗炎免疫药物工程技术研究中心,安徽省高校中药抗炎免疫药理学科技创新团队,安徽省中药研究与开发重点实验室,安徽合肥230032

出　　处：《中国药理学通报》2008年第3期330-335,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30572356);安徽省自然科学基金资助项目(No050430903);安徽省高等学校青年教师科研基金资助项目

摘　　要：目的 研究芍药苷（paeoniflofin，Pae）对胶原诱导性关节炎（collagen-induced arthritis，CIA）大鼠滑膜细胞G蛋白偶联信号转导的调节作用。方法用鸡Ⅱ型胶原诱导胶原性关节炎。在免疫后d 16～23，胶原性关节炎大鼠灌胃给予Pae（25、50、100mg·kg^-1）。通过足爪肿胀和关节炎指数评价关节炎。采用Western blot技术检测滑膜细胞中抑制性G蛋白（Gi）表达。用放免法检测滑膜细胞中cAMP水平，用激酶发光分析法测定滑膜细胞中蛋白激酶A（PKA）的活性。结果胶原性关节炎大鼠出现明显的继发性炎症反应。滑膜细胞中Gi蛋白表达增加，而cAMP水平和PKA活性明显降低。Pae抑制胶原性关节炎大鼠的炎症应答。在100mg·kg^-1，Pae抑制Gi的表达。在50mg·kg^-1和100mg·kg。剂量，Pae提高cAMP水平和PKA活性。体外研究发现，Pae（2．5、12．5、62．5mg·L^-1）降低滑膜细胞中Gi的表达，而提高降低的cAMP水平和PKA活性。结论胶原性关节炎大鼠滑膜细胞中G蛋白偶联的信号转导与滑膜炎病理机制密切相关；Pae对胶原性关节炎大鼠的抗炎作用是通过调节G蛋白偶联的信号转导实现的。Aim To investigate the of Paeoniflorin on G protein-coupled regulatory effects signaling by synoviocytes of collagen-induced arthritis （ CIA ） rats. Methods CIA was induced by chicken type II collagen. Pae （25, 50, 100 mg · kg^-1） was administered to CIA rats from d 16 to d 23 after immunization. Arthritis was evaluated by hind paw swelling and arthritis index. Expression of inhibitory G protein （Gi） was detected by Western blotting technique. The level of cAMP in synoviocytes was measured by radioimmunoassay. Protein kinase A （PKA） activity was assessed by Kinase-Glo Luminescent Kinase Assay. Results There was remarkably secondary inflammation in CIA rats. The expression of Gi in synoviocytes in-creased. While cAMP level and PKA activity of syno- viocytes decreased. The inflammatory responses of CIA rats were inhibited after administration of Pae. At the dose of 100 mg · kg^-1, Pae reduced Gi expression. cAMP level and PKA activity were enhanced by Pae at the doses of 50 and 100 mg · kg^-1 respectively. In ivtro, Pae （2.5, 12.5, 62.5 mg· L^-1） reduced Gi expression, but enhanced the level of cAMP and PKA activity. Conchmion G protein-coupled signaling was associated with the pathogenesis of synovitis in CIA rats. Pae has anti-inflammatory effects on CIA rats by modulating G protein - coupled signaling.

关 键 词：芍药苷 胶原性关节炎 滑膜细胞 信号转导 G蛋白 

分 类 号：R-332[医药卫生] R284.1