生长相关蛋白-43磷酸化及神经生长因子在膀胱过度活动症发病机制中的作用

Role of GAP-43’s phosphorylation and NGF in OAB

目的研究生长相关蛋白-43(GAP-43)在膀胱过度活动症患者膀胱的表达及其磷酸化和神经生长因子(NGF)在膀胱过度活动症发病机制中的作用。方法应用Western blot方法检测32例膀胱过度活动症患者膀胱组织及10例正常膀胱组织和10例其他原因所致尿频患者膀胱组织中GAP-43的表达及其蛋白质磷酸化,32例OAB患者中,13例为特发性逼尿肌不稳定(IDI),19例为特发性感觉急迫(SU)。应用酶联免疫吸附试验(ELISA)测量正常和特发性逼尿肌不稳定膀胱标本中NGF的含量。结果 Western blotting结果显示,在NC膜上43kD处均有阳性的反应条带,正常膀胱和其他原因尿频膀胱反应带微弱;而OAB组反应条带明显加深,OAB组与对照组间的差异有显著性(P<0.05)。同样,磷酸化的结果也表明OAB组表达高于对照组,差异有显著性(P<0.05)。不稳定膀胱组,平均NGF含量为(1.06±0.11)pg/μg蛋白,而正常膀胱组为(0.58±0.07)pg/μg蛋白,两者相比,差异有显著性(P<0.05)。结论 GAP-43在OAB膀胱中的表达量较正常膀胱显著增多,提示神经的发芽生长和再建重塑与膀胱过度活动症有关,而磷酸化的GAP-43对这些过程有重要调节作用。NGF在人膀胱生理学和病理学方面起重要作用,可能参与不稳定膀胱的发病机制。

【Objective】To study the expression of GAP-43 in bladder from OAB and the role of its protein phosphorylation in the pathogenesis of OAB.To study mechanisms which might regulate NGF.【Methods】The expression of GAP-43 and its protein phosphorylation were detected by western blotting in 32 cases of OAB and 10 cases of normal bladder tissue and 10 cases of patient with urge syndrome led by other cause.In OAB,there were 13 cases of IDI and 19 cases of SU.The NGF content in samples from 10 normal bladder and 10 IDI were measured using enzymelinked immunosorbent assay.【Results】Western blotting data indicated that the positive band was around 43 kD on NC membrane,the reaction was weaker in the controls and deeper significant in IDI and SU,there was significant difference between OAB and controls （P 0.05）.Protein phosphorylation data indicated the same results,there was significant difference between two groups （P 0.05）.The mean NGF content was significant higher in IDI,at （1.06±0.11） pg/μg protein ,than in the normal bladder,at （0.58±0.07） pg/μg protein,there was significant difference between two groups（P 0.05）.【Conclusions】There was significant increases in GAP-43 in bladders from patients with OAB compared to controls.It suggests that neural sprouting and/or remodeling be related to OAB.Phosphorylation of GAP-43 regulates these procedure.These data suggest that NGF functions in the physiology and pathophysiology of the human bladder,it might involve with pathogenesis of IDI.