Han Jong Soo, Kim Su Jin, Nam Yoonjin, Lee Hak Yeong, Kim Geon Min, Kim Dong Min, Sohn Uy Dong
Signaling and Pharmacological Activity Research Lab, College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea.
Biomol Ther (Seoul). 2019 Jan 1;27(1):101-106. doi: 10.4062/biomolther.2018.136.
Most diabetic patients experience diabetic mellitus (DM) urinary bladder dysfunction. A number of studies evaluate bladder smooth muscle contraction in DM. In this study, we evaluated the change of bladder smooth muscle contraction between normal rats and DM rats. Furthermore, we used pharmacological inhibitors to determine the differences in the signaling pathways between normal and DM rats. Rats in the DM group received an intraperitoneal injection of 65 mg/kg streptozotocin and measured blood glucose level after 14 days to confirm DM. Bladder smooth muscle contraction was induced using acetylcholine (ACh, 10⁻⁴ M). The materials such as, atropine (a muscarinic receptor antagonist), U73122 (a phospholipase C inhibitor), DPCPX (an adenosine A₁ receptor antagonist), udenafil (a PDE5 inhibitor), prazosin (an α₁-receptor antagonist), papaverine (a smooth muscle relaxant), verapamil (a calcium channel blocker), and chelerythrine (a protein kinase C inhibitor) were pre-treated in bladder smooth muscle. We found that the DM rats had lower bladder smooth muscle contractility than normal rats. When prazosin, udenafil, verapamil, and U73122 were pre-treated, there were significant differences between normal and DM rats. Taken together, it was concluded that the change of intracellular Ca²⁺ release mediated by PLC/IP3 and PDE5 activity were responsible for decreased bladder smooth muscle contractility in DM rats.
大多数糖尿病患者会出现糖尿病性膀胱功能障碍。许多研究评估了糖尿病患者膀胱平滑肌的收缩情况。在本研究中，我们评估了正常大鼠和糖尿病大鼠膀胱平滑肌收缩的变化。此外，我们使用药理学抑制剂来确定正常大鼠和糖尿病大鼠信号通路的差异。糖尿病组大鼠腹腔注射65mg/kg链脲佐菌素，14天后测量血糖水平以确认糖尿病。使用乙酰胆碱（ACh，10⁻⁴M）诱导膀胱平滑肌收缩。将阿托品（一种毒蕈碱受体拮抗剂）、U73122（一种磷脂酶C抑制剂）、DPCPX（一种腺苷A₁受体拮抗剂）、伐地那非（一种磷酸二酯酶5抑制剂）、哌唑嗪（一种α₁受体拮抗剂）、罂粟碱（一种平滑肌松弛剂）、维拉帕米（一种钙通道阻滞剂）和白屈菜红碱（一种蛋白激酶C抑制剂）等物质预先处理膀胱平滑肌。我们发现糖尿病大鼠的膀胱平滑肌收缩力低于正常大鼠。当预先使用哌唑嗪、伐地那非、维拉帕米和U73122处理时，正常大鼠和糖尿病大鼠之间存在显著差异。综上所述，得出结论：PLC/IP3和磷酸二酯酶5活性介导的细胞内Ca²⁺释放变化是糖尿病大鼠膀胱平滑肌收缩力降低的原因。
