Chen Yen-Cheng, Ho Ching-Chun, Yi Chih-Hsun, Liu Xiu-Zhu, Cheng Tzu-Ting, Lam Chen-Fuh
Department of Surgery, Buddhist Tzu Chi General Hospital, Hualien, Taiwan.
Department of Internal Medicine, Buddhist Tzu Chi General Hospital, Hualien, Taiwan.
PLoS One. 2017 Nov 2;12(11):e0187434. doi: 10.1371/journal.pone.0187434. eCollection 2017.
Diabetes mellitus is an independent risk factor for impaired healing of peptic ulcers, and there are currently no supplementary therapeutics other than the standard antipeptic medicine to improve the ulcer healing in diabetes. This study examined the potential pleiotropic effect of a glucagon-like peptide (Glp)-1 analogue exendin (Ex)-4 on the regeneration of gastric ulcer in streptozotocin-induced diabetic rats.
Chronic ulcer was created in rat stomach by submucosal injection of acetic acid and peri-ulcer tissues were analyzed 7 days after operation. Ulcer wound healing was impaired in diabetic rats with suppressed tissue expression of eNOS and enhanced levels of pro-inflammatory reactions. Treatment with intraperitoneal injection of Ex4 (0.5 μg/kg/d) significantly reduced the area of gastric ulcer without changing blood glucose level. Ex-4 restored the expression of pro-angiogenic factors, and attenuated the generation of regional inflammation and superoxide anions. The improvement of ulcer healing was associated with increased expression of MMP-2 and formation of granulation tissue in the peri-ulcer area.
Administration of Ex4 may induce pro-angiogenic, anti-inflammatory and anti-oxidative reactions in the peri-ulcer tissue of diabetic rats that eventually enhances tissue granulation and closure of ulcerative wounds. Our results support the potential clinical application of Glp-1 analogues as supplementary hypoglycemic agents in the antipeptic ulcer medication in diabetes.
糖尿病是消化性溃疡愈合受损的独立危险因素，目前除标准抗溃疡药物外，尚无其他辅助治疗方法可改善糖尿病患者的溃疡愈合。本研究探讨了胰高血糖素样肽（Glp）-1类似物艾塞那肽（Ex）-4对链脲佐菌素诱导的糖尿病大鼠胃溃疡再生的潜在多效性作用。
通过黏膜下注射乙酸在大鼠胃中制造慢性溃疡，并在术后7天分析溃疡周围组织。糖尿病大鼠的溃疡伤口愈合受损，伴有内皮型一氧化氮合酶（eNOS）组织表达受抑制和促炎反应水平升高。腹腔注射Ex4（0.5μg/kg/d）治疗可显著减小胃溃疡面积，而不改变血糖水平。Ex-4恢复了促血管生成因子的表达，并减轻了局部炎症和超氧阴离子的产生。溃疡愈合的改善与溃疡周围区域基质金属蛋白酶-2（MMP-2）表达增加和肉芽组织形成有关。
给予Ex4可能在糖尿病大鼠溃疡周围组织中诱导促血管生成、抗炎和抗氧化反应，最终增强组织肉芽形成和溃疡伤口闭合。我们的结果支持Glp-1类似物作为辅助降糖药物在糖尿病抗溃疡治疗中的潜在临床应用。
