摘要
目的:探讨过氧化物酶体增殖物活化型受体((peroxisome proliferator-activated receptor gamma,PPARγ)激动剂吡格列酮防治痛风性关节炎的可行性及机制。方法:于大鼠单侧踝关节腔内注射1 mg(20 mg/ml×50μl)尿酸钠晶体(monosodi-um urate,MSU)建立急性痛风性关节炎模型。以RT-PCR法检测PPARγ在关节炎滑膜0、4、8、24和48 h表达的动态变化。通过比较2、4、6、8、10、12、24和48 h关节炎症、肿胀、功能障碍指数和病理变化观察口服不同剂量(4 mg.kg-1.d-1、20 mg.kg-1.d-1)吡格列酮对关节炎的影响。结果:关节滑膜PPARγ表达呈时间依赖方式增加,在关节炎48 h后尤为明显。在诱发模型24 h内,吡格列酮对关节炎未见明显作用;而在48 h大剂量吡格列酮可显著减低关节炎的炎症、肿胀、功能障碍指数和滑膜炎性细胞浸润,但小剂量疗效不明显。结论:大剂量吡格列酮可显著减轻大鼠急性痛风性关节炎。关节炎后期PPARγ表达增加有利于药物起效和痛风的自发缓解。
Objective：To study the feasibility and mechanism of pioglitazone,an agonist of peroxisome proliferator-activated receptor y（PPARγ） in resolution of monosodium urate monobydrate（MSU） crystal-induced arthritis. Methods： A rat model of acute gouty arthritis was induced with the injection of lmg （20 mg/ml× 50μ） MSU into rat ankle joint cavity. Dynamic mRNA expressions of PPARγ in synovium at 0 h,4 b,8 b,24 h and 48 h after MSU injection were determined by reverse transcriptasepolymerase chain reaction （RT-PCR）. The effects of pioglitazone （4 mg·kg^-1·d^-1 and 20 mg · kg^-1·d ^-1 ） on arthritis were investigated through assessing clinical features and histopathologic changes in rats at 2 b,4 b,6 b,8 b,10 b,12 h,24 h and 48 h after arthritis induction. Results： The mRNA expression of PPARγ in synovium of rats with arthritis was significantly increased in a time-dependent manner and peaked at 48 b after MSU injection. The anti-arthritis effects of pioglitazone were not significant during 24 b after induction, and high dose other than low dose of pioglitazone significantly ameliorated the inflammation, swell ing, disability index and histopathologic changes at 48 h after MSU injection in rats. Conclusion： Pioglitazone has obvious anti inflammatory properties in gouty arthritis. Elevated expression of PPARγ in synovium after arthritis induction may contribute to effects of PPARγ agonist and resolution of acute attacks of gout.
出处
《第二军医大学学报》
CAS
CSCD
北大核心
2005年第12期1380-1383,共4页
Academic Journal of Second Military Medical University
