摘要
目的初步探索沙培林膀胱灌注治疗的安全性、有效性和作用机制。方法 (1)临床研究:收集膀胱肿瘤术后行沙培林膀胱灌注治疗的患者40例,检测灌注前后尿液中细胞因子IL-2、TNF-α、INF-γ的含量,术后6个月复查膀胱镜。(2)动物实验:取雌性大鼠75只,分为空白对照组(15只)、生理盐水灌注组(15只)、沙培林灌注组(15只)、BCG灌注组(15只)和大肠杆菌灌注组(15只),每周灌注治疗一次,6周后停止灌注。从每组中随机选取10只大鼠,处死后取其膀胱三角区组织做病理切片,观察并比较免疫细胞浸润情况,同时行免疫组化分析,检测IL-2、TNF-α、INF-γ在组织中的表达情况。剩余25只大鼠不做任何处理,饲养2个月后全部处死,取其膀胱三角区组织做病理切片,观察停止灌注后膀胱组织是否出现慢性炎性改变。结果 (1)临床研究:膀胱肿瘤术后膀胱灌注沙培林,尿中细胞因子IL-2、TNF-α、INF-γ均显著升高。6个月后复查膀胱镜见炎性改变且均未见肿瘤复发,不良反应发生率低。(2)动物实验:膀胱灌注6周后大鼠膀胱免疫细胞浸润情况与细胞因子IL-2、TNF-α、INF-γ的表达相似:大肠杆菌组>沙培林组≈BCG组>生理盐水组>空白对照组;停止膀胱灌注2个月后,大肠杆菌组表现为膀胱炎性改变,其余各组几乎均表现为正常尿路上皮。结论沙培林与BCG等免疫调节剂作用机制相似,通过引起膀胱上皮炎性反应,增强病变部位的免疫功能,从而识别并清除变异细胞,且在一段时间后能自行恢复为正常尿路上皮,不引起慢性炎性改变,沙培林是一种安全、有效的免疫调节剂。
Objective To investigate the efficacy,safety and the mechanism of intravesical instillation of OK-432（sapylin）by the clinical observation and animal＇s experiment. Methods（1）Clinical research：40cases diagnosed with bladder tumor which used OK-432（sapylin）for intravesical instillation in the postoperative period were collected,and determing the content of cytokine TNF-α,INF-γand IL-2in the urine collected before and after infusion respectively,reviewing the cystoscopy 3months after operation,and counting the adverse effects.（2）Animal experiment：divided75female rats into five groups：blank control group（15）,saline perfusion group（15）,sapylin perfusion group（15）,BCG vaccine perfusion group（15）,E.coli perfusion group（15）,perfusion treatment once a week,continuous 6weeks,then selected 10 rats from each group randomly,killed the rats and took the trigone tissue for pathological salices and immunohistochemical analysis of cytokine TNF-α,INF-γand IL-2.The rest 25 rats just raised after 2 months without any treatment,after 2months killed the rest rats and took the trigone tissue for pathological salices. Results（1）Clinical research：the content of urine cytokine TNF-α,INF-γand IL-2,after perfusion of OK-432（sapylin）rose significantly,after 6months reviewed the cystoscopy and reported inflammatory changes,no tumor recurrence,and low incidence of adverse reactions.（2）Animal experiment：after 6weeks intravesical instillation with different solutions,infiltration of immune cell in the rat bladder tissue and expression of cytokines TNF-α,INF-γand IL-2were similar：E.coli group sapylin group ≈BCG group saline group blank control group;stopped perfusion 2 months was shown as：E.coli group characterized by bladder inflammatory change,almost all the rest of the group was turn to normal transitional epithelium.Conclusions Sapylin＇s action mechanism is similar with BCG,mainly through activating the bladder epithelial inflammatory reaction enhance the immune function of the lesion site,and than recognize and eliminate the mutant cells,and can recover to normal transitional epithelium after a period of time,therefore sapylin is a kind of safe and effective immune regulator.
出处
《现代泌尿生殖肿瘤杂志》
2016年第6期345-349,共5页
Journal of Contemporary Urologic and Reproductive Oncology
关键词
沙培林
膀胱灌注
膀胱肿瘤
细胞因子
Sapylin
Intravesical instillation
Bladder tumor
Cytokines
