Department of Pharmacology, College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea.
Arch Pharm Res. 2020 Jun;43(6):666-675. doi: 10.1007/s12272-020-01244-z. Epub 2020 Jun 30.
Dysfunction of gastrointestinal (GI) motility is a common complication in patients with diabetes mellitus (DM). Studies related to changes in fundus contraction induced by inhibitors in DM are not well known. Therefore, this study aimed to investigate the signaling pathways involved in the changes in the contraction of fundus smooth muscle obtained from control and DM rats. DM was induced by injecting streptozotocin (65 mg/kg) into Sprague-Dawley rats. The rats were sacrificed after 14 days. Fundus smooth muscle contraction was stimulated using electrical field stimulation (amplitude, 50 V; duration, 1 min; frequency, 2-20 Hz) and acetylcholine (0.1 mM). The inhibitor-mediated cell membrane was pre-treated with atropine, verapamil, methysergide, ketanserin, ondansetron, and GR 113808. Inhibitors related to intracellular signaling, such as U73122, chelerythrine, L-NNA, were also used. ML-9 and Y-27632 were identified as inhibitors of factors of myosin light chain (MLC). The contractility was observed to be lower in the DM group than in the control group. Further, the activities of phospholipase C (PLC), protein kinase C (PKC), and myosin light chain kinase (MLCK) were decreased in the DM group. DM reduced the activity of PLC, PKC, and MLCK, which resulted in a decrease in the contractility of the fundus smooth muscle. Therefore, our results present the mechanism of this DM-mediated GI disorder.
胃肠道（GI）运动功能障碍是糖尿病（DM）患者的常见并发症。关于 DM 中抑制剂诱导的胃底收缩变化的相关研究尚不清楚。因此，本研究旨在探讨参与对照组和 DM 大鼠胃底平滑肌收缩变化的信号通路。通过向 Sprague-Dawley 大鼠注射链脲佐菌素（65mg/kg）诱导 DM。大鼠在第 14 天被处死。使用电刺激（幅度，50V；持续时间，1 分钟；频率，2-20Hz）和乙酰胆碱（0.1mM）刺激胃底平滑肌收缩。用阿托品、维拉帕米、麦角乙脲、酮色林、昂丹司琼和 GR 113808预处理抑制剂介导的细胞膜。还使用了与细胞内信号相关的抑制剂，如 U73122、Chelerythrine、L-NNA。ML-9 和 Y-27632 被鉴定为肌球蛋白轻链（MLC）因子的抑制剂。与对照组相比，DM 组的收缩力较低。此外，DM 组的磷脂酶 C（PLC）、蛋白激酶 C（PKC）和肌球蛋白轻链激酶（MLCK）活性降低。DM 降低了 PLC、PKC 和 MLCK 的活性，导致胃底平滑肌收缩力降低。因此，我们的结果提出了这种 DM 介导的胃肠道紊乱的机制。
