百里醌对胶原诱导大鼠关节炎模型中氧化应激和炎症因子的影响研究

Effect of Thymoquinone on Oxidative Stress and Inflammatory Cytokine in Rats with Collagen Induced Arthritis

本研究探讨百里醌对胶原诱导大鼠关节炎(RA)模型的抗氧化和抗炎机理。实验采用60只Wistar大鼠随机分为6组,分别为正常对照组、模型对照组、阳性对照组、百里醌低、中和高剂量组,每组10只。除正常对照组外,采用II型胶原(CIA)诱导大鼠RA模型。阳性对照组灌胃给予8 mg/kg吲哚美辛,百里醌各剂量组分别给予低(10 mg/kg)、中(25 mg/kg)和高(50 mg/kg)三种剂量的百里醌灌胃,其余各组给予等体积的生理盐水,连续21日。足趾容积法测定大鼠关节继发性肿胀程度。测定机体关节组织中氧化损伤与抗氧化指标髓过氧化物酶(MPO)、丙二醛(MDA)、超氧化物歧化酶(SOD)和一氧化氮(NO)。ELISA法测定血清炎症因子白介素-1β(IL-1β)、肿瘤坏死因子α(TNF-α)和IL-6的水平。结果发现25 mg/kg和50 mg/kg的百里醌有效缓解II型胶原引起的足趾肿胀,降低RA发病中MPO、MDA和NO的含量,升高组织中SOD的水平,与模型对照组相比,差异具有显著性(P<0.05)。此外,百里醌可以显著降低RA大鼠血清IL-1β和TNF-α的含量,促进IL-10表达(P<0.05)。综上,百里醌可以有效缓解RA的症状,其机制与维持机体氧化-抗氧化体系的平衡和对抗前炎症因子导致的组织破坏相关。

This study aimed to evaluate mechanisms concerning the antioxidant and antiarthritic effects of thymoquinone on collagen-induced rat arthritis （RA） model. Sixty Wistar rats were randomly divided into a normal control group, a model control group, a pasitive control group, a low-dose, a medium-dose and a high-dose thymoquinone group （n = 10）. RA model,except for the normal control group,was established by being induced by type II collagen. For 21 continuous days,the three thymoquinone groups were intragastrically administered with low-dose （10 mg/kg）,medium-dose （25 mg/kg） and high-dose （50 mg/kg） thymoqninone,the positive control group was intragastrically administered with 8 mg/kg indometacin,and other groups were intragastrically administered with same volume of normal saline. Secondary joint swelling of the rats was determined by a paw volume method. Biochemical indices for oxidative damage, including levels of myeloperoxidase （ MPO ）, malondialdehyde （ MDA ）, superoxide dismntase （SOD） and nitric oxide （NO）, were detected. ELISA assay was used to measure the levels of serum intlarmnatory cytokine interleukin-1β （IL-1β）, tumor necrosis factor-α （TNF-α） and IL-10. The results showed that 25 mg/kg and 50 mg/kg of thymoquinone remarkably re- lieved type II collagen-induced articular swelling, decreased the levels of MPO, MDA and NO, and increased the SOD ac- tivity, being significantly different from those of the model control group （P 〈 0.05）. In addition, thymoqninone signifi- cantly lowered the contents of IL-1β and TNF-α in serum and promoted the expression of IL-10 （P 〈0.05）. In conclu- sion, thymoquinone managed to effectively mitigate RA with the mechanism related to the maintained balance between oxidation and antioxidation as well as the suppressed tissue lesions caused by proinflammatory eytokines.