医用热硫化硅橡胶免疫抑制效应的评价

Evaluation of medical heat vulcanizing silicone rubber's immunosuppressive effects

背景:目前,关于医疗器械或生物材料免疫毒性的评价体系及相应的评价方法、有效的动物模型研究较少。目的:建立免疫抑制毒性小鼠模型,并针对医用热硫化硅橡胶的免疫毒性进行初筛和评价。设计、时间及地点:随机对照实验,于2007-09/11在上海交通大学医学院附属第九人民医院,上海生物材料研究测试中心完成。材料:SPF级6～8周龄健康C57BL/6小鼠18只。环磷酰胺购于Sigma公司,医用热硫化硅橡胶由上海橡胶制品研究所提供。方法:18只小鼠按随机数字表法分为3组,医用热硫化硅橡胶组、阳性对照组、空白对照组,每组6只。空白对照组仅行皮下埋植手术创伤处理。医用热硫化硅橡胶组皮下埋植薄片状医用热硫化硅橡胶(直径12mm、厚度1mm)。阳性对照组行皮下埋植手术创伤处理,腹腔注射环磷酰胺25mg/kg,连续28d。主要观察指标:28d后取小鼠胸腺、脾脏,计算胸腺/体质量比值、脾脏/体质量比值,脾脏病理表现,脾脏细胞总数及外周血白细胞总数变化。结果:18只小鼠全部进入结果分析。阳性对照组胸腺/体质量比值、脾脏/体质量比值、脾脏细胞总数及白细胞总数明显低于空白对照组,差异有显著性意义(P<0.05),医用热硫化硅橡胶组以上指标的变化与空白对照组差异无显著性意义(P>0.05)。阳性对照组脾脏病理表现为脾小体的生发中心消失,医用热硫化硅橡胶组变化不明显。结论:成功建立了评价免疫毒性的免疫抑制研究模型,在此评价体系下医用热硫化硅橡胶无明显的免疫毒性。

BACKGROUND： So far, there isn＇t any set of evaluation system and animal models on medical devices or biomaterials＇ immunotoxicity. OBJECTIVE： To build an immunosuppressive mouse model, primarily screen and evaluate the immunotoxicity of medical heat vulcanizing silicone rubber. DESIGN, TIME AND SETTING： A randomized controlled study was conducted at Shanghai Ninth People＇s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Biomaterials Research ＆ Testing Center from September to November in 2007. MATERIALS： Eighteen healthy C57BL/6 mice of 6-8 weeks old, SPF grade, were used in this study. Cyclophosphamide was purchased from Sigma, and medical heat vulcanizing silicone rubber was provided by Shanghai Rubber Products Institute. METHODS： Eighteen C57BL/6 mice were randomly assigned into 3 groups, with 6 mice in each group. Blank control group received surgical insult only. Sample group received subcutaneous implantation with medical heat vulcanizing silicone rubber （1 mm diameter and 12 mm length）. Positive control group received surgical insult and cyclophosphamide （25 mg/kg） for 28 successive days. MAIN OUTCOME MEASURES： Mouse thymus and spleen were harvested 28 days later to measure the ratio of immune organ （thymus/spleen） to body weight, splenic pathology, total amount of spleen lymphocytes and total amount of leukocytes in peripheral blood. RESULTS： All 18 animals were involved in the final analysis. Compared with the blank control group, ratio of immune organ （thymus/spleen） to body weight, total amount of spleen lymphocytes, total amount of leukocytes in peripheral blood in the positive control group decreased significantly （P 〈 0.05）, while no such changes were observed in the sample group （P 〉 0.05）. In histological examination of spleen, germinal centers were not observed in the positive control group, but were observed in the sample group. CONCLUSION： An animal model of immunosuppressive effects of immunotoxicity was set up successfully. Under the evaluation system established, the medical heat vulcanizing silicone rubber showed no significant immunotoxic effect.