从TLR4 /cAMP信号传导通路研究尿感方清除受感染膀胱上皮细胞胞内UPEC的作用机制

反复发作和耐药菌株增多是尿路感染（UTI）防治面临的重点和难点，尿道致病性大肠杆菌（UPEC）侵袭膀胱上皮细胞（BECs）成为细胞内寄生菌是导致UTI反复发作的主要因素之一。最新研究显示，TLR4/cAMP信号传导通路是介导受感染BECs清除胞内UPEC的关键通路，本课题在前期研究证明治疗UTI的有效方剂尿感方能增强受感染BECs清除胞内UPEC作用的基础上，提出“对TLR4 /cAMP信号传导通路的调节是尿感方清除受感染BECs胞内UPEC的作用机制”的假说。. 本研究采用体内尿路感染动物模型和体外细胞感染模型，运用微生物学、细胞学和分子生物学技术，研究尿感方及其拆方清除受感染BECs胞内UPEC的作用特点和对受感染BECs TLR4 /cAMP信号传导通路主要环节的影响，综合比较分析尿感方及其拆方在不同环节的作用特点和协同作用点，剖析尿感方清除受感染BECs胞内UPEC的作用机制。

The main challenges in preventing and curing urinary tract infections (UTIs), primarily induced by Uropathogenic Escherichia coli(UPEC) invading bladder epithelial cells (BECs) and becoming intracellular parasitic bacteria, are recurrent and delayed healing. TLR4/cAMP has been elucidated, in the latest research, as the crucial signaling pathway mediating the expulsion of intracellular UPEC from infected BECs, and the expulsion can be promoted by Niaogan Fang which has been validated in our previous study to have the ability to effectively cure urinary tract infections. We here put forward the hypothesis that the mechanism of Niaogan Fang regulating the expulsion of intracellular UPEC from infected BECs was based on the regulation of TLR4/cAMP signaling pathway. . For the elucidation of the hypothesis, we would focus on and analysis the relationship of the characteristics of Niaogan Fang in expulsion of intracellular UPEC from infected BECs and the key marker of TLR4 /cAMP signaling pathway, based on the in vivo and in vitro infection models. We can finally clarify the mechanism of Niaogan Fang in expulsion of intracellular UPEC from infected BECs by application of versatile approaches from multidiscipline, such as microbiology, cytology, molecular biology, etc. In addition, this project would be of value in triggering more interest in its related area of many researchers.