紫杉醇对胶原诱导性关节炎小鼠血管新生抑制作用的研究
发布时间：2018-04-19 19:55
本文选题：类风湿关节炎 + 胶原诱导性关节炎 ； 参考：《南方医科大学》2017年硕士论文
【摘要】：背景血管新生是类风湿关节炎(rheumatoid arthritis,RA)的重要特征之一,在RA滑膜血管翳的形成和生长中起着核心作用,不可控的新生血管形成可以导致炎细胞浸润、滑膜组织增生,最终导致软骨和骨破坏,因此延缓或阻断RA患者的滑膜血管新生已成为RA治疗的重要靶点之一。胶原诱导性关节炎(collagen-inducedarthritis,CIA)模型的临床表现、发病机理、病理特征等方面与人RA相似,是研究RA的理想动物模型。本课题用中药红豆杉提取物紫杉醇(taxol,PTX)干预CIA小鼠,研究PTX对CIA小鼠滑膜血管新生的作用。目的研究PTX对CIA小鼠滑膜血管新生及VEGF、HIF-1α表达的影响。方法用50只C57BL/6(H-2b)小鼠诱导CIA模型,造模后关节炎评分大于4分的CIA 小鼠被随机分为 1.5mg/kg PTX 组、1.0mg/kg PTX 组、0.5mg/kg PTX 组及CIA模型组,每组6只,另外6只未造模的正常小鼠作为正常对照组。干预组分别予对应剂量的PTX隔日腹腔注射,对照组予等体积溶媒,共给药8次。运用视觉模拟评分法对小鼠关节炎进行评分;HE染色后对小鼠关节组织进行病理学评分(从滑膜炎、血管翳和骨破坏三个方面评估);免疫组化法检测关节滑膜组织微血管的密度(microvessel density,MVD)以及血管内皮生长因子(vascular endothelial growth factor,VEGF)、低氧诱导因子 1α(hypoxia-inducible factor-α,HIF-1α)的表达;ELISA检测小鼠外周血清VEGF和HIF-1α的表达。结果PTX干预组关节炎评分分别为1.33±0.52、2.00±0.63、3.33±1.03,与CIA模型组(5.67±1.03)比较显著降低,差异均有统计学意义(P0.001,P0.001,P=0.016)。PTX干预组关节病理总评分分别为2.50±0.66、3.89±0.86、6.22±0.98,呈剂量依赖性减少,与CIA模型组(7.67±0.79)比较显著降低,差异均有统计学意义(P0.001,P0.001,P=0.007)。并且PTX能明显减少(CIA小鼠关节病理滑膜炎、血管翳及骨破坏评分。与CIA模型组(110.32±5.06/mm2)相比,PTX干预组的MVD亦呈剂量依赖性降低(17.05±1.97/mm2,34.73±2.36/mm2,57.55±2.72/mm2,P均0.001)。此外,1.5mg/kgPTX 组(42.38±3.22)、1.Omg/kg PTX 组(74.30±4.14)、0.5mg/kgPTX 组(121.69±3.81)滑膜组织的 VEGF 表达低于CIA模型组(156.22±4.75;P均0.001);1.5mg/kg PTX组(19.93±2.92)和1.0mg/kg PTX组(31.99±5.60)的滑膜组织HIF-1α表达低于CIA模型组(51.10±2.86;P均0.001)。1.5mg/kg PTX 组(10.70±1.21pg/ml)和 1.0mg/kg PTX组(14.75±0.96pg/ml)的外周血清 VEGF 表达低于 CIA 模型组(16.40±1.43pg/ml,P 均0.001),且 1.5mg/kg PTX 组(2.17±0.43pg/ml)和 1.0mg/kg PTX 组(3.47±0.51pg/ml)外周血清 HIF-1α 表达亦低于 CIA 模型组(5.07±1.19pg/ml,P0.001,P=0.032)。MVD与关节病理滑膜炎、血管翳、骨破坏评分及滑膜组织VEGF、HIF-1α 的表达水平均呈正相关(r=0.921,r=0.944,r=0.889,r=0.969,r=0.933;P均0.001)。结论PTX能抑制CIA小鼠滑膜血管新生,并降低滑膜组织和外周血清VEGF、HIF-1α的表达水平,PTX可能通过降低VEGF、HIF-1α的表达抑制CIA小鼠滑膜血管生成。
[Abstract]:Background Angiogenesis is one of the important characteristics of rheumatoid arthritis (RA), which plays a central role in the formation and growth of synovial pannus. Uncontrolled angiogenesis can lead to inflammatory cell infiltration and synovial tissue proliferation. Finally, cartilage and bone damage are caused, so delaying or blocking synovial angiogenesis in RA patients has become one of the important targets of RA therapy. The collagen-induced arthritis (CIA) model is similar to that of human RA in clinical manifestations, pathogenesis and pathological features. It is an ideal animal model for the study of RA. To study the effect of PTX on synovial angiogenesis in CIA mice, Taxolus taxolatus extract from Taxus cuspidata was used to interfere with CIA mice. Objective to study the effect of PTX on synovial angiogenesis and expression of VEGF HIF-1 伪 in CIA mice. Methods CIA models were induced in 50 C57BL / 6H-2b mice. CIA mice with arthritis score greater than 4 were randomly divided into 1.5mg/kg PTX group (1.0 mg / kg PTX group) and CIA model group (0.5 mg / kg PTX group), with 6 mice in each group and 6 normal mice as normal control group. The intervention group received intraperitoneal injection of corresponding dose of PTX every other day, while the control group received the same volume solvent for 8 times. Using Visual Analog scoring method to score Arthritis in mice with HE staining and pathological grading of Mouse Joint tissue (from synovitis, synovitis, synovitis, synovitis, synovitis, synovitis, The expression of VEGF and HIF-1 伪 in peripheral blood of mice were detected by immunohistochemistry. The expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor (VEGF) and hypoxia-inducible factor- 伪 (HIF-1 伪) were detected by immunohistochemistry. Results the arthritis score of PTX intervention group was 1.33 卤0.52 卤0.63 卤3.33 卤1.03, which was significantly lower than that of CIA model group (5.67 卤1.03), and the difference was statistically significant (P 0.001 P 0.001P 0.001P 0.001P 0.016). The total score of joint pathology in PTX-treated group was 2.50 卤0.663.89 卤0.866.22 卤0.98, decreased in a dose-dependent manner, and was significantly lower than that in CIA model group (7.67 卤0.79). The difference was statistically significant (P 0.001 P 0.001 P 0.001 P 0. 007). And PTX significantly reduced the score of synovitis, pannus and bone destruction in mice. Compared with the CIA model group, MVD in the PTX-treated group decreased in a dose-dependent manner (17.05 卤1.97 / mm ~ 34.73 卤2.36 卤2.36 / mm ~ (-2) 卤57.55 卤2.72 / mm ~ (-2) P) in a dose-dependent manner. 姝ゅ,1.5mg/kgPTX 缁，
本文编号：1774495
本文链接：https://www.wllwen.com/yixuelunwen/nfm/1774495.html
最近更新
教材专著
