Zhao Yi, Chang Zhi-Fang, Li Ru, Li Zhan-Guo, Li Xiao-Xia, Li Lin
Department of Rheumatology and Allergy, Xuanwu Hospital, Capital Medical University Beijing 100053, China.
Department of Rheumatology & Immunology, Peking University People's Hospital Beijing 100044, China.
Am J Transl Res. 2016 Nov 15;8(11):5044-5051. eCollection 2016.
To reevaluate the suppressive effect of paclitaxel (PTX) liposome on collagen-induced arthritis (CIA) in rats and explore its mechanisms.
Female Lewis rats were immunized with bovine type II collagen (CII) to induce arthritis. The rats with CIA were randomly divided into three groups: 5% GS control group, 2.5 mg/kg PTX treatment group and 1 mg/kg methotrexate (MTX) positive control group. The drugs were administered by intraperitoneal injection on the second day after arthritis onset. The body weights, arthritis scores and paw volumes were observed consecutively. The ankle joints of rats were collected for X-ray examination and histological evaluation. Serum samples were collected to test the levels of anti-CII antibodies and cytokines.
Body weights were not significantly affected after PTX or MTX treatments (>0.05). Compared with 5% GS control or MTX treatment groups, PTX group showed significant decrease of arthritis scores and paw volumes (p<0.05). Radiographic and histologic evaluation provided evidence that rats with PTX treatment had less synovial proliferation and bone erosion. In addition, the levels of anti-CII antibodies as well as serum tumor necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF) levels were remarkably lower in PTX group than those in 5% GS controls (<0.05).
PTX inhibits the progression of CIA in rats and prevents the destruction of joints. The mechanism might be related to its inhibition on the levels of serum anti-CII antibodies, TNF-α and VEGF.
重新评估紫杉醇(PTX)脂质体对大鼠胶原诱导性关节炎(CIA)的抑制作用并探讨其机制。
用牛II型胶原(CII)免疫雌性Lewis大鼠以诱导关节炎。将患CIA的大鼠随机分为三组:5%葡萄糖注射液对照组、2.5mg/kg PTX治疗组和1mg/kg甲氨蝶呤(MTX)阳性对照组。在关节炎发作后第二天通过腹腔注射给药。连续观察大鼠体重、关节炎评分和足爪体积。收集大鼠踝关节进行X线检查和组织学评估。采集血清样本检测抗CII抗体和细胞因子水平。
PTX或MTX治疗后体重无显著影响(>0.05)。与5%葡萄糖注射液对照组或MTX治疗组相比,PTX组关节炎评分和足爪体积显著降低(p<0.05)。影像学和组织学评估表明,PTX治疗的大鼠滑膜增生和骨侵蚀较少。此外,PTX组抗CII抗体水平以及血清肿瘤坏死因子(TNF)-α和血管内皮生长因子(VEGF)水平明显低于5%葡萄糖注射液对照组(<0.05)。
PTX可抑制大鼠CIA的进展并防止关节破坏。其机制可能与其抑制血清抗CII抗体、TNF-α和VEGF水平有关。