高强度聚焦超声对B7-CD28共刺激通路的影响

摘要

Objective:To investigate whether HIFU therapy could active T cells and enhance IL-2 level in serum by affecting B7-CD28 costimulatory pathway,and ultimately result in the induction of the anti-tumor immunological reaction.Methods:Rat osteosarcoma models constructed by orthotopic technique were treated with HIFU,and then were detected the percentage of CD4+ CD28 +,CD4 + CD28-,CD80 + and CD86 + cell subset in splenocyte by FCM and IL-2 level by ELISA in the different time points (immediate moment,2th day,5th day,15th day after HIFU treatment).The lung metastasis of rat models were detected by histopathological technique before and after HIFU treatment.Results:In comparison with osteosarcoma group,the cell subset of CD4 + CD28 +,CD4 + CD28-,CD80 + in HIFU groups obviously increased(P ＜ 0,05 or P ＜ 0.01);CD86 + cell subset was increased at the immediate moment and second day after HIFU,but had no significance.However,CD86 + cell subset decreased on fifth day and fifteenth day after HIFU therapy;IL-2 level of HIFU groups obviously enhanced (P ＜ 0.05 or P ＜ 0.01).The cell subset above of HIFU groups were significantly higher than normal group (P ＜ 0.05 or P ＜ 0.01);IL-2 level of HIFU groups was obviously increased (P ＜ 0.05 or P ＜ 0.01).Compared with the HIFU control group,the cell subset above in HIFU groups (second day and fifth day after HIFU therapy) significantly increased (P ＜ 0.05 or P ＜ 0.01).The metastasis in lung of osteosarcoma rats after HIFU therapy obviously decreased or even vanished,compared to untreated group.Conclusion:It might be one of mechanism that HIFU therapy can enhance the immunologic function of rat by activating B7-CD28 pathway.%目的:探讨高强度聚焦超声(high intensity focused ultrasound,HIFU)是否通过影响B7-CD28共刺激通路使T细胞活化,血清IL-2水平升高,引起抗肿瘤免疫反应.方法:采用原位移植法构建大鼠骨肉瘤模型后,用HIFU治疗机进行辐照,分别在治疗后即刻、2天、5天、15天行流式细胞术,检测脾细胞中CD4+ CD28+、CD4+ CD28-、CD80+、CD86+细胞亚群所占的比例,ELISA检测血清IL-2水平,行病理组织学观察HIFU治疗后的大鼠的肺部转移灶情况.同时设立阴性对照、正常对照、空白对照组.结果:HIFU各组CD4+ CD28+、CD4+ CD28-、CD80+细胞亚群比治疗前明显增高(P＜0.05或P＜0.01);CD86+细胞亚群在HIFU治疗后即刻、2天有增高,均无统计学意义,而治疗后5天、15天有降低;HIFU各组IL-2水平比治疗前明显增高(P＜0.05或P＜0.01).与正常组相比,HIFU各组上述细胞亚群明显增高(P＜0.05或P＜0.01);HIFU各组IL-2水平均有明显增高(P＜0.05或P＜0.01).与HIFU对照组(25天)相比,HIFU组(2、5天)各细胞亚群均增高(P＜0.05或P＜0.01);HIFU后5天IL-2水平有显著差异(P＜0.05).HIFU治疗后骨肉瘤大鼠肺部转移灶比治疗前明显减少或消失.结论:HIFU治疗骨肉瘤后激活B7-CD28通路可能是免疫功能提高的机制之一.