腺苷酸活化蛋白激酶(AMPK)在膀胱出口梗阻引起的失代偿性膀胱中的功能及作用机制

BPH is a highly prevalent nonmalignant enlargement of the prostate related to ageing,and evidence of BPH can be found in 50% of men in their 60s. It is the most common case of bladder outlet obstruction in adult male.If the blockage lasts a long time,the bladder begins to fail and may lead to bladder decompensation or irreversible bladder dysfunction.However,the mechanisms for the development of bladder outlet obstruction is still remains unknown.The AMP-activated protein kinase (AMPK) is a major regulator of cellular and whole-body energy homeostasis that coordinates metabolic pathways. Sevaral reports mentioned that AMPK are associated with several diseases.Recently,AMPK is also emerging as a new important regulator for the bladder.In this study,to investigate the funtion and regulation mechanism of AMPK in bladder outlet obstruction (BOO)-induced bladder alterations,we will establish disease-specific animal models,use urodynamic study to observing and grouping bladder alterations. Several molecular approaches will be used to evaluate the expression and releated signalling cascades in bladder outlet obstruction, including immunofluorescence histochemistry staining、 confocal laser scanning microscopy and western blot.In vivo and in vitro study will be done for evaluating the bladder funtion and for expounding the regulation mechanisms of AMPK in bladder outlet obstruction，Which related with PKC,Rho-Rho kinase pathway.Our findings may suggest that altered expression profile of AMPK contributes to the development of BOO, and may motivate testing of drugs with the potential curative effect in bladder outlet obstruction.

前列腺增生作为男性老化过程的一种改变。在60岁以上男性中约有50%的人会出现前列腺增生。这也是导致膀胱出口梗阻最常见的病因。由于长时间的出口梗阻，膀胱从最初的代偿期到后期的失代偿期，会出现多种病理生理学改变。然而，其相关机制尚不清楚。AMPK是调节细胞和全身能量内稳态及协调代谢通道的重要作用因子。课题组在综合分析了AMPK在多种疾病中的诸多分子机制以及相关信号转道通路的基础上，结合预实验数据，推测AMPK在膀胱出口梗阻导致的膀胱病变中发挥重要作用。本研究拟应用尿动力学检查技术，分析并阶段性分组膀胱出口梗阻的发展过程。应用蛋白印迹、免疫组化等方法检测AMPK与PKC,Rho kinase通路细胞因子在膀胱出口梗阻中的阶段性表达及阐明相关信号转导通路，以分子生物学结果为基础，通过体内和体外相关激活剂/抑制剂实验，综合分析AMPK在出口梗阻膀胱中的作用及作用机制。为膀胱出口梗阻的治疗提供新思路。