沙培林膀胱灌注的临床观察及实验研究
Study of intravesical instillation with sapylin on the clinical observation and animal experiment
王宁 1卫超 1MusaMale 1王珅 1彭鄂军 1叶章群 1陈志强1
作者信息
- 1. 430030 武汉,华中科技大学附属同济医院泌尿外科
- 折叠
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.
Abstract
Objective To investigate the efficacy,safety and the mechanism of intravesical in-stillation of OK-432 (sapylin)by the clinical observation and animal's experiment. Methods ①Clinical research:40 cases diagnosed with bladder tumor which used OK-432 (sapylin)for intravesi-cal instillation in the postoperative period were collected,and determing the content of cytokine TNF-α,INF-γand IL-2 in the urine collected before and after infusion respectively,reviewing the cystoscopy 3 months after operation,and counting the adverse effects.②Animal experiment:divided 75 female rats into five groups:blank control group (15),saline perfusion group (15),sapylin per-fusion group (15),BCG vaccine perfusion group (15),E.coli perfusion group (15),perfusion treat-ment once a week,continuous 6 weeks,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 2 months killed the rest rats and took the trigone tissue for pathological salices. Results ①Clinical research:the content of urine cytokine TNF-α,INF-γand IL-2,after perfusion of OK-432 (sapylin)rose significantly,after 6 months reviewed the cystoscopy and reported inflammatory changes,no tumor recurrence,and low incidence of adverse reactions.②Animal experiment:after 6 weeks intravesical instillation with different solutions,infiltration of immune cell in the rat bladder tissue and expression of cytokines TNF-α,INF-γand IL-2 were similar:E.coli group > sa-pylin 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 re-action 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.
关键词
沙培林/膀胱灌注/膀胱肿瘤/细胞因子Key words
Sapylin/Intravesical instillation/Bladder tumor/Cytokines引用本文复制引用
出版年
2016
NETL
NSTL
维普
万方数据