目的 观察尿感方抗尿道致病性大肠杆菌（uropathogenic Escheriehia coli，UPEC）侵袭膀胱上皮细胞的作用，并探讨其作用机制。方法 通过UPEC感染人膀胱癌细胞5637（human bladder cancer cell 5637，HTB-9）侵袭模型，观察尿感方含药尿液保护膀胱上皮细胞抗UPEC侵袭的作用；同时采用分子生物学技术，观察其对Toll样受体4（TLR4）/环磷酸腺苷（cAMP）信号传导通路的主要环节：TLR4、腺苷酸环化酶3（AC3）、环磷酸腺苷（cAMP）、蛋白激酶A（PKA）和Rac-1的影响。结果 与大鼠空白尿液高剂量组（体积分数10%空白尿液）比较，尿感方大鼠含药尿液高剂量组（体积分数10%含药尿液）的细菌入侵率降低；与模型组比较，大鼠空白尿液组的细菌入侵率无显著性差异。与大鼠空白尿液高剂量组比较，尿感方大鼠含药尿液高剂量组增加了TLR4、AC3蛋白的表达及胞内cAMP的水平，促进了PKA活化，抑制了Rac-1的活性。结论 尿感方具有一定的抗UPEC侵袭膀胱上皮细胞的作用，其作用机制与影响TLR4/cAMP信号传导通路的环节有关。

Objective To observe the role of Niaogan Prescription against uropathogenic Escheriehia coli(UPEC) in invading bladder epithelial cells, and to discuss its mechanism of action.Methods After HTB-9 infected with UPEC, the cell invasion model was used to observe the protective effects of drug urine in human bladder cancer cell 5637(HTB-9) against UPEC invasion.Effects of Niaogan Prescription on the main steps of signaling pathway:Toll-like receptor 4(TLR4), adenylate cyclase 3(AC3), cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), and Rac-1 was investigated by molecular biology techniques.Results Compared with the blank urine high dose group (10% volume fraction of blank urine), treatment with the drug-containing urine high dose group of Niaogan Prescription (10% volume fraction of drug urine) resulted in a significant decrease in UPEC invasion, the bacterial invasion rate of the rat blank urine group had no significant difference compared with the model group.Compared with the blank urine high dose group, the drug-containing urine high dose group of Niaogan Prescription improved TLR4 and AC3 protein expression, increased intracellular cAMP content, promoted PKA activation, and inhibited Rac1 activity.Conclusion Niaogan Prescription have the certain capacity against UPEC invasion of bladder epithelial cells, which mechanism is related to TLR4/cAMP signaling pathway.

国家自然科学基金资助项目（81403168）