普罗布考对实验性大鼠急性痛风性关节炎的防治
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青岛市科技局重大项目(06-2-2-3-nsh-1)


Role of Probucol in Resolution of Monosodium Urate Monohydrate Crystal Induced Acute Gouty Arthritis of Rat
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    摘要:

    目的探讨普罗布考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尿酸钠晶体建立急性痛风性关节炎模型,观察普罗布考干预后关节炎症、肿胀指数及关节液白细胞计数和白细胞介素1β的变化。用尿酸盐晶体刺激人单核细胞,普罗布考干预18h后检测培养液中白细胞介素1β的浓度。结果普罗布考各剂量组关节炎症肿胀指数下降幅度由低剂量向高剂量依次增加,与模型组比较,72h时中高剂量组下降程度较明显(P<0.05),关节液白细胞计数和白细胞介素1β的含量均有不同程度的下降。普罗布考中高剂量组关节液白细胞计数较模型组下降明显(P<0.01,P<0.001),普罗布考高剂量组白细胞介素1β较模型组下降明显(P<0.05)。普罗布考各剂量组对单核细胞分泌白细胞介素1β无抑制作用。结论中高剂量的普罗布考可以有效的控制大鼠急性痛风性关节炎的发作,其疗效具有一定的剂量依赖性,但其不是通过直接抑制单核细胞摄取尿酸盐晶体分泌白细胞介素1β来起作用。

    Abstract:

    Aim To study the feasibility and mechanism of probucol in resolution of monosodium urate monohydrate (MSU) crystal-induced arthritis. Methods A rat model of acute gouty arthritis was induced with the injection of MSU into rat ankle joint cavity. The effects of probucol on arthritis were investigated through observing clinical features,the synovial fluid white blood cell count and interleukin-1β(IL-1β). IL-1β concentration of culture medium was observed after the 18 h intervention with probucol in THP-1 monocytes while stimulated by MSU. Results The degree of joint swelling decreased gradually from probucol low-dose group to high-dose group and there was signifanct difference between mid-dose and hign-dose probucol groups and model group at 72h(P<0.05). The synovial fluid white blood cell count and IL-1β declined in varying degrees in probucol groups compar with the model group. Synovial fluid white blood cell count of probucol mid-dose and high-dose group decreased significantly,comparing with the model group (P<0.01,P<0.001). IL-1β of probucol high-dose group decreased significantly comparing with the model group (P<0.05). Probucol group showed no inhibition on IL-1β secretion of the THP-1 human monocyte cells. Conclusion The mid-dose and hign-dose probucol can effectively control acute gouty arthritis attack and the effect is dependent on dose,but the effect is not produced by inhibiting IL-1β secretion of THP-1 monocytes after the uptaking the MSU.

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罗艳,袁鹰,李长贵,陈红.普罗布考对实验性大鼠急性痛风性关节炎的防治[J].中国动脉硬化杂志,2008,16(10):767~770.

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  • 收稿日期:2008-09-23
  • 最后修改日期:2008-10-25
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