青藤碱对胶原诱导性关节炎大鼠滑膜血管新生的影响

The Influene of Sinomenine on Synovial Angiogenesis in Rats with Collagen-induced Arthritis

目的研究青藤碱对胶原诱导性关节炎(Collagen induced arthritis,CIA)大鼠滑膜血管新生的影响。方法Wister大鼠48只,随机分为正常组、模型组、甲氨蝶呤组和青藤碱组,每组12只。采用Ⅱ型胶原溶液制备类风湿性关节炎大鼠模型,建模周期14 d,建模成功后,各组大鼠开始灌胃给药。青藤碱组0.04 g/kg,每日1次,连续42 d;甲氨蝶呤组0.002 g/kg,每7天1次,连续42 d;正常组和模型组给予等体积生理盐水,每日1次,连续42 d。分别在初次免疫35、56 d时,检测大鼠足跖肿胀度,血清肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)、白细胞介素-17(Interleukin-17,IL-17)的含量,踝关节滑膜微血管密度(Microvessel density,MVD)、血管内皮生长因子(Vascular endothelial growth factor,VEGF)、内皮抑素(Endostatin,ES)的表达。结果与正常组比较,模型组大鼠初次免疫后7、14、35、56 d的足跖肿胀度升高,模型组大鼠35、56 d的血清TNF-α、IL-17含量升高、滑膜MVD、VEGF表达升高,ES表达降低,差异均有统计学意义(P<0.05);与模型组比较,甲氨蝶呤组和青藤碱组大鼠35、56 d的足跖肿胀度降低,血清TNF-α的含量均下降,滑膜MVD、VEGF表达降低,ES表达升高,差异均有统计学意义(P<0.05)。与模型组比较,甲氨蝶呤组大鼠35、56 d的血清IL-17含量降低,差异有统计学意义(P<0.05)。结论青藤碱对CIA大鼠滑膜血管新生有较好的抑制作用,可能与其抑制TNF-α产生,降低滑膜VEGF的表达,提高ES的表达有关。

Objective To study the effect and mechanism of Sinomenine on synovial angiogenesis in collagen-induced arthritis(CIA)rats.Methods 48 Wister rats were randomly divided into normal group,model group,Methotrexate group and Sinomenine group.Rheumatoid arthritis rat model was prepared withⅡtype collagen solution.The modeling period was 14 days.After the model was successfully established,the treatment groups were given intragastric administration with corresponding drugs for 42 days.On the 35th day and the 56th day after initial immunization,the voix pedis swelling,TNF-αand IL-17 levels in rat serum,the expression of MVD,VEGF and ES in the ankle joint synovium were tested.Results Compared with the normal group,the voix pedis swelling in the model group was more obvious,TNF-αand IL-17 levels in rat serum were increased,MVD and VEGF expression of synovium was increased,ES expression was decreased,and the differences were statistically significant(P<0.05).Compared with the model group,the voix pedis swelling in Sinomenine group was obviously decreased,TNF-αlevels in rat serum and expression of MVD and VEGF of synovium were decreased,the expression of ES was increased,and the differences were statistically significant(P<0.05).Conclusion Sinomenine has a better inhibitory effect on synovial angiogenesis in CIA rats,which may be related to the decreasing of TNF-αcontent in serum and VEGF expression in synovium,increasing of ES expression.