蛋白酶体抑制剂MG132改善胶原诱导性关节炎模型大鼠炎症反应的研究

Proteasome inhibitor MG132 attenuates inflammation changes in collageninduced arthritis rat

目的:观察蛋白酶体抑制剂MG132对牛Ⅱ型胶原诱导性关节炎大鼠炎症相关因子的影响。方法:48只雌性SD大鼠随机分为对照组、关节炎模型组、MG132干预组。于大鼠左足趾部皮内注射牛Ⅱ型胶原构建关节炎模型,干预组在关节炎模型基础上于皮下注射MG132进行干预。建模后每周观察大鼠关节肿胀程度,并计算关节炎指数。第42天处死大鼠,取大鼠踝关节进行HE染色观察其病理改变;用酶联免疫吸附试验(ELISA)检测大鼠血清中TNF-α、IL-6、IL-10的水平。结果:牛Ⅱ型胶原成功诱导大鼠关节炎病变,MG132干预明显降低了关节炎指数,减少关节损坏、滑膜组织细胞增生及炎症反应,同时降低大鼠血清TNF-α、IL-6表达水平(P<0.01),提高IL-10表达水平(P<0.01)。结论:MG132能减轻胶原诱导性大鼠关节炎相关炎症指标,调节胶原诱导性关节炎模型大鼠血清促炎因子与抑炎因子的表达平衡,改善其炎症症状。

Objective:To observe the anti-inflammatory effects of proteasome inhibitor MG132 in bovine typeⅡcollagen-induced arthritis rat.Methods:A total of 48 female Sprague-Dawley(SD)rats were randomly divided into three groups:including mock,collagen and MG132 intervention group.The arthritis model group was established by intradermal injection of bovine typeⅡcollagen into the left toe of rats.The intervention group was intervened by subcutaneous injection of MG132 on the basis of the arthritis model.The degree of joint swelling was observed every week and the arthritis index was calculated.The rats were sacrificed on the 42nd day,the ankle joints were stained with HE and the serum levels of TNF-α,IL-6 and IL-10 were detected with ELISA.Results:Bovine typeⅡcollagen successfully induced arthritis in rats.MG132 intervention significantly reduced arthritis index,joint damage,synovial tissue cell proliferation and inflammatory reaction.At the same time,MG132 intervention reduced TNF-αand IL-6 produce(P<0.01);however,the IL-10 were improved in the group(P<0.01).Conclusion:MG132 can regulate the expression balance of serum proinflammatory factors and anti-inflammatory factors in collagen induced arthritis model rats and improve their inflammatory symptoms.