伊班膦酸盐对小鼠抗原诱导性关节炎炎症的影响。

Effects of ibandronate on inflammation in mouse antigen-induced arthritis.

作者信息

Zysk S P, Dürr H R, Gebhard H H, Schmitt-Sody M, Refior H J, Messmer K, Veihelmann A

机构信息

Department of Orthopaedics, Ludwig-Maximilians-University of Munich, Klinikum Grosshadern, Marchioninistr. 15, 81377 Munich, Germany.

出版信息

Inflamm Res. 2003 May;52(5):221-6. doi: 10.1007/s000110300075.

DOI:10.1007/s000110300075

PMID:12813627

Abstract

OBJECTIVE

To investigate the effects of ibandronate, a novel aminobisphosphonate, on inflammation as well as leukocyte-endothelial cell interaction in mouse antigen-induced arthritis (AiA).

MATERIAL AND TREATMENT

36 Balb/c mice were subcutaneously injected with 160 microg/kg of ibandronate once per day beginning at day 7 until day 13 after induction of AiA.

METHODS

The severity of arthritis was assessed by changes of the transverse knee joint diameter. For the intravital fluorescence microscopy measurements on day 14 after AiA induction, the patella tendon was partly resected to visualize the intraarticular synovial tissue of the knee joint. The number of rolling and adherent leukocytes as well as red blood cell (RBC) velocity and functional capillary density (FCD) were quantified in synovial microvessels. Furthermore, leukocyte infiltration in the synovium was determined in histological sections with an established score.

RESULTS

Both fractions of rolling leukocytes (p = 0.016) as well as number of extravasated leukocytes (p = 0.004) were enhanced in control animals treated with ibandronate in comparison to animals which received saline. Arthritic animals with and without ibandronate treatment revealed an increased FCD (p = 0.006, p = 0.008), enhanced number of rolling ( p = 0.002, p = 0.001) and adherent leukocytes (p = 0.009, p = 0.007) and greater swelling of the left knee joint (p = 0.002, p = 0.001) when compared to control animals. No significant differences between arthritic animals and arthritic animals treated with ibandronate were found in any of the parameters assessed including leukocyte adherence, FCD, histology, and knee joint swelling.

CONCLUSION

Ibandronate treatment of healthy mice was associated with an enhanced fraction of rolling leukocytes and increased numbers of extravasated leukocytes indicating a proinflammatory effect on the synovial microcirculation. In animals with a preexisting antigen-induced arthritis, however, ibandronate did not induce an exacerbation of joint inflammation and leukocyte adherence.

摘要

目的

研究新型氨基双膦酸盐伊班膦酸钠对小鼠抗原诱导性关节炎（AiA）炎症以及白细胞与内皮细胞相互作用的影响。

材料与处理

36只Balb/c小鼠，在诱导AiA后第7天开始，每天皮下注射160μg/kg伊班膦酸钠，直至第13天。

方法

通过膝关节横径变化评估关节炎严重程度。在诱导AiA后第14天进行活体荧光显微镜测量时，部分切除髌腱以观察膝关节内滑膜组织。对滑膜微血管内滚动和黏附白细胞数量、红细胞（RBC）流速及功能性毛细血管密度（FCD）进行定量分析。此外，通过既定评分在组织学切片中测定滑膜内白细胞浸润情况。

结果

与接受生理盐水的动物相比，接受伊班膦酸钠治疗的对照动物滚动白细胞比例（p = 0.016）及渗出白细胞数量（p = 0.004）均增加。与对照动物相比，接受和未接受伊班膦酸钠治疗的关节炎动物均显示FCD增加（p = 0.006，p = 0.008）、滚动白细胞数量增加（p = 0.002，p = 0.001）和黏附白细胞数量增加（p = 0.009，p = 0.007），且左膝关节肿胀更明显（p = 0.002，p = 0.001）。在包括白细胞黏附、FCD、组织学和膝关节肿胀等评估的任何参数中，关节炎动物与接受伊班膦酸钠治疗的关节炎动物之间均未发现显著差异。