目的探讨含笑内酯对类风湿关节炎DBA/1小鼠模型的治疗作用。方法将40只6周龄雄性DBA/1小鼠随机分为4组:未处理的空白对照组(Nor组)、诱导发病并注射甲氨蝶呤药物的甲氨蝶呤治疗组(MTX组)、诱导发病并注射含笑内酯的实验组(MCL组)和诱导发病并注射DMSO的模型对照组(Con组),用牛Ⅱ型胶原法诱导MTX、C0n和MCL组小鼠发病建立类风湿关节炎模型;在二次免疫注射24h后开始隔天腹腔注射给药并对小鼠体重和关节炎发病情况进行隔天观察,给药28次后停止用药,眼球取血、蛋白芯片测血清中细胞因子,处死小鼠取爪子及膝盖做组织病理学检查。结果成功构建了DBA/1小鼠类风湿关节炎模型;各组小鼠之间体重差异无统计学意义(P〉0.05);关节炎评价显示MCL组低于Con组(P〈0.01),高于MTX组(P〈0.01);病理结果显示Nor组小鼠组织正常.Con组受累关节m现炎症细胞浸润、滑膜增生、炎性肉芽组织形成、坏死组织等症状,MCL组与MTX组受累关节仅出现轻于Con组的炎症细胞侵润、滑膜增生等症状;小鼠血清细胞因子检测结果共显示m6种细胞因子:C5/C5a、TIMP-1、M—CSF、sICAM-1、IFN-吖和BLC;Con组的类风湿关节炎小鼠中C5/C5a、TIMP-1和M—CSF表达量降低,经含笑内酯治疗的MCL组中这些因子均有不同程度的恢复(P〈0.01),仅仅在MCL组中检测到BLC表达。结论含笑内酯对小鼠DBA/1类风湿关节炎具有治疗作用,C5/C5a、TIMP-1、M—CSF和BLC等因子在这-过程发挥不同的作用。
Objective To investigate the therapeutic efficacy of micheliolide (MCL) in the DBA/1 mice CIA model. Methods 40 cases of 6 weeks of DBA/1 male mice were randomly divided into 4 groups. The normal control group (group Nor) did not receive any treatment, the other three groups were induced to arthritis model by using immunization grade bovine type Ⅱ collegen: 24 hours after the secondalT immunization began to intraperitoneal injection by two days once, the positive control group (group MTX) was treated with methotrexate (MTX), the experiment group (group MCL) was treated with MCL, while the negative control group (group Con) was treated with DMSO. On the first intraperitoneal injection day, the four groups" mice on their weight and the evaluation of arthritis were began to test for once two days. Administration after having 28 times intraperitoneal injection was stopped for 4 times of test. The blood for mouse cy- tokine array test was taken, the mice were executed, the paws were taken and the pathology analysis was did. Results It was suceessed for building the CIA mice model; the result of weight test showed that there had no difference between eaeh group (P 〉 0.05); the evaluation of arthritis displayed that the MCL group was lower than that in the group Con (P〈 0.01) and higher than the group MTX (P 〈 0.01); the pathological result showed that the normal joint tissue present from the group Nor, the synovitis cell infiltration, the hyperplasia of synovial cell, formation of granulation tissue and the necrotic tissue are present in the group Con, while the group MCL and the group MTX only pre-sented synovitis cell infiltration, the hyperplasia of synovial cell and so on, and both of them were milder than the group Con; there were six eytokines tested in this experiment, and they were marked as 1 to 6. Cytokine 1 to 6 were all shown in the four groups, they were C5/C5a, TIMP-1, M-CSF, sICAM-1, IFN-γ, BLC. The result of M-CSF and TIMP-1 are the same to C5/C5a, which