膀胱灌注5-氨基酮戊酸诱导内生PpⅨ荧光的组织分布  

Biodistribution of 5-Aminolevulinic Acid Induced PpⅨ in Various Tissues of Bladder Wall after Intravesical Instillation of 5-Aminolevulinic Acid

作　　者：宋晓东[1] 叶章群[1] 周四维[1] 杨为民[1] 刘继红[1] 马扬之[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院泌尿外科,武汉市430030

出　　处：《中国激光医学杂志》2005年第4期228-232,共5页Chinese Journal of Laser Medicine & Surgery

摘　　要：目的通过膀胱灌注5-氨基酮戊酸(5-ALA)探讨其所诱导产生内源性PpⅨ在膀胱组织中分布及不同病变表达上的差异.方法 20例无痛性肉眼血尿患者行荧光膀胱镜检查.以50 ml 5-ALA缓冲液膀胱灌注,2～3 h后置入荧光膀胱镜,用光动力学诊断系统进行荧光膀胱镜检,采用407 nm激发光照射膀胱壁,对产生荧光的红色区域及非荧光的蓝色区域分别进行标记活检,取活检组织做快速冰冻切片,每块组织均做2份,1份用HE染色进行组织病理学检查,另1份用甘油封闭后在激光共聚焦显微镜下荧光成像,分析各标本荧光分布并定量检测不同组织PpⅨ荧光含量.结果共取活检组织32处,病理检查结果,膀胱移行细胞癌共18处、良性病变12处、正常膀胱上皮2处.激光共聚焦显微镜下所见,5-ALA诱导PpⅨ荧光主要分布在组织表层,深部组织PpⅨ荧光很弱.荧光量化分析显示,表层组织荧光强度高出深部组织5～10倍,对比各样本表层组织荧光,其强度与肿瘤分级相关(G3> G1-2),而肿瘤组织平均荧光强度明显高于良性病变的平均荧光强度.结论 (1)由于PpⅨ荧光主要分布在组织表层,荧光膀胱镜检只能发现表层的病变,因此对于位于正常膀胱黏膜下的病变进行荧光诊断可能无价值,在荧光膀胱镜指示下行经尿道切除术(TUR)时,对于切除深度无指导意义.(2)5-ALA诱导荧光膀胱镜检对膀胱癌诊断特异性尚不高,但量化荧光强度可区分良、恶性病变,从而提高荧光膀胱镜检对肿瘤诊断的特异性.(3)PpⅨ可作为肿瘤标志物来判断肿瘤生物学行为.(4)激光共聚焦显微镜及其图像分析系统对于膀胱肿瘤光动力学诊断(PDD)临床应用价值的分析是一个很有用的工具.ABSTRACT Objective To investigate histological distribution of PpⅨ after intravesical instillation of 5-ALA and difference of PpⅨ expression in different lesions. Methods Twenty patients with painless gross hematuria were examined by fluorescence cystoscopy. One and a half grams of 5-aminolevulinic acid were dissolved in 50 ml of 1.4% sodium bicarbonate solution, then instill 5-ALA solution into bladder. After 2-3 hours, put in fluorescence cystoscope, perform fluorescence cystoscopy using photodynamic diagnosis（PDD） systems, 407 nm excitated light is used to irradiate bladder wall. Perform biopsy at red fluorescence areas and non-fluorescence blue areas, respectively, make 2 freezesections of each biopsy specimen, one for HE staining, the other for determining fluorescence distribution and fluorescence intensity of PpⅨ in different tissues by laser confocal fluorescence microscopy after glycerine blocking. Results Pathology analysis showed, among 32 biopsy specimens, 18 were transitional cell carcinoma, 14 were benign lesions. Under laser confocal fluorescence microscopy, 5-ALA induced PpⅨ fluorescence distributed mainly in surface layer of tissues, on the contrary, fluorescence in deep layer was weak. Fluorescence analysis showed that fluorescence intensity in surface tissues was 5-10 times higher than that of deep tissues, mean fluorescence intensity of tumor tissues was higher than that of benign lesions and had statistically significance with tumor grades（ G3 〉 G1-2 ）. Conclusions （ 1 ） As fluorescence of PpⅨ mainly distributes in tissue surface layer, fluorescence cystoscopy could only find surface lesions, so it might have no meaning to diagnosis of lesions beneath normal mucosa, and could not guide in determining resection depth of bladder tumor during transurethral resection （TUR） under fluorescence cystoscope. （2） 5-ALA induced fluorescence cystoscopy＇s specificity to bladder cancer diagnosis is not enough high, but fluorescence intensity could discriminate between beni

关 键 词：膀胱癌 光动力学诊断 荧光膀胱镜 活组织检查 5-氨基酮戊酸 激光共聚焦显微镜 

分 类 号：R737.14[医药卫生—肿瘤] R318.51[医药卫生—临床医学]