Bladder outlet obstruction (BOO) is one of the most common diseases in urology. As the disease progresses, collagen deposits in the bladder wall and bladder fibrosis appears, which destroys the delicate structure of the bladder and affects the function of bladder. However, there is still no satisfactory method to relieve the bladder fibrosis secondary to BOO. Metformin is a classic AMPK agonist, which was proved to alleviate the inflammatory response by inhibiting the TGF-β pathway and reducing oxidative stress as well as  inhibit the abnormal deposition of collagen effectively in the processes of liver fibrosis, kidney fibrosis and lung fibrosis. In this study, we evaluated the role of metformin in bladder fibrosis caused by BOO.

Female Sprague Dawley rats were anesthetized and the surgical area was disinfected. Then a sterile catheter with an outer diameter of 1 mm was lubricated and inserted through the urethra. The catheter was ligated around the urethra with silk thread and then the catheter was removed and the incison was closed. The untreated group and the sham operated group served as controls. Rats in BOO group were treated with metformin (400mg / kg) orally or an equivalent amount of drinking water every day after the operation. 8 weeks later, the  inflammation condition as well as the structure of the bladder were observed.

The level of activation of the TGF-β / Smad pathway was increased in BOO rats. The inflammation was more serious and more collagen deposited in the bladder wall, which promoted the hypertrophy of the bladder wall. Metformin taken orally inhibits the activation of TGF-β / Smad pathway in the bladders of BOO rats. The bladders from BOO rats who took metformin orally showed reduced level of inflammation and less deposition of collagen in the bladders.

We found that the occurrence of BOO was accompanied by increases in the level of  TGF-β / Smad pathway activation as well as in collagen deposition in the bladder wall. The oxidative stress in the bladders was also elevated. BOO rats taking metformin orally showed less TGF-β / Smad pathway activation and less collagen deposition. BOO rats treated with metformin suffered less from BOO.

We supposed that orally administration of metformin could inhibit BOO-induced activation of TGF-β / Smad pathway and inhibit collagen deposition in the bladder wall, alleviating bladder fibrosis. The results showed that oral administration of metformin could ameliorate bladder fibrosis in BOO rats, which provides a new idea for clinical treatment of bladder fibrosis secondary to BOO.