腎上腺素接受器對於下泌尿道重塑時間質上皮轉化機制之影響
郭萌享，陳志碩，林威宇，何東儒，黃雲慶，林健煇，黃國財，邱國雄
嘉義長庚醫院 外科部 泌尿外科
The Effect of Adrenergic Receptor on Mesenchymal-Epithelial Transition inLow Urinary Tract Remodeling Diseases
Meng-Hsiang Kuo, Chih-Shou Chen, Wei-Yu Lin, Dong-Ru Ho, Yun-Chin Huang,
Pey-Jium Chang, Jian-Hui Lin, Kuo-Tsai Huang, Kuo-Hsiung Chiu
Division of Urology, Department of Surgery Chang Gung Memorial Hospital, Chia-Yi, Taiwan
Purpose: Adrenergic receptors have previously played a critical role in treatment of benign prostate hyperplasia, and recently also become important in management of overactive bladder. Drugs targeting these receptors may relieve bladder outlet obstruction or relax bladder spasm. These treatments had been widely used for long period of time. Recent findings of their roles in epithelial-mesenchymal transition (EMT) have also come on the stage, which may affect long term low urinary tract remodeling process. We evaluated the role of adrenergic receptor on bladder remodeling through EMT in this study
Materials and Methods: We evaluate how beta-adrenergic receptor affects epithelial mesenchymal transition with animal model. We used the well-established interstitial cystitis overactive bladder (IC) rat model by treating the rats with intraperitoneal cyclophosphamide. Rats were divided into five groups, including control group, IC group, IC with beta adrenergic antagonist group (IC+P, propranolol), bAR agonist treated IC group (IC+B3Ag, beta-3 adrenergic agonist), bAR agonist/ antagonist treatment group (IC+P+B3Ag), and bAR agonist treatment only group (B3Ag). Urodynamic studies and von Frey tactile sensitivity test was checked to confirm IC establishment. Bladders was retrieved for evaluation of inflammatory and EMT markers in Western blotting and immunohistochemistry studies.
Results: Lower segment of bladder, which is near trigone, express the most amount of beta adrenergic receptor. Low abdominal tactile hypersensitivity best indicates IC model establishment. Specific beta adrenoceptor agonist promotes E-cadherin expression, while IC rats may promote EMT and result in remodeling of subendothelium interstitial cells. Once beta-adrenoceptor antagonist is added, the effect of B3Ag are diminished. These changes, along with EMT markers, may be demonstrated along with bladder remodeling
Conclusion: Once bladder remodeling occurred, it indicates an irreversible change. Beta-3 adrenergic receptor agonist seemed to be a potential solution for the initiation of EMT. Besides, it seemed to work better in disease active status. The local inflammatory reaction is more associated with innate immunity, while less related with systemic inflammatory factor TNFa. In our model, EMT biomarkers do not always take two sides. Interstitial inflammation is very prominent in IC rats. However, both E-cadherin and Vimentin expression decreased in these rats. Even so, we can still notice persistent E-cadherin expression when beta-3 adrenergic agonist is used. In the future treatment of inflammatory overactive bladder, we expected B3Ag to play a more important role.