Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, China.
Diabetes Res Clin Pract. 2012 Sep;97(3):453-60. doi: 10.1016/j.diabres.2012.04.001. Epub 2012 May 5.
To determine whether exendin-4 might directly improve endothelial dysfunction in aorta isolated from high-fat diet-induced obese rats.
Wistar rats were randomly divided into control and obesity (OB) groups and fed. Vascular segments of obese rats were incubated in organ bath in the presence or absence of exendin-4. Nitric oxide (NO) production and nuclear transcription factor kappa B expression in vascular rings were measured. The aortic rings of the obese rats were then incubated in an organ bath with exendin-4 in the presence or absence of the following inhibitors: the AMPK, the adenylate cyclase and the NO synthase inhibitor.
The maximum endothelium-dependent vasodilatation (EDV) value was severely reduced in the OB group. Exendin-4 treatment significantly increased the NO level, improved endothelium-dependent vasodilatation and reduced expression of NF-κB in the obese group. The beneficial effect of exendin-4 on EDV in obese rats was partly attenuated in the presence of the specific inhibitors.
Exendin-4 directly improves impaired EDV of aortae from obese rats. The beneficial effect of exendin-4 appears to be mediated in part via stimulation of cAMP/AMPK-related signalling pathways and enhancement of endothelial nitric oxide synthase activity.
确定 exendin-4 是否可以直接改善高脂饮食诱导肥胖大鼠主动脉内皮功能障碍。
将 Wistar 大鼠随机分为对照组和肥胖组（OB 组）并进行喂养。在存在或不存在 exendin-4 的情况下，将肥胖大鼠的血管段孵育在器官浴中。测量血管环中一氧化氮（NO）的产生和核转录因子κB 的表达。然后，将肥胖大鼠的主动脉环在存在或不存在以下抑制剂的情况下在器官浴中孵育：AMPK、腺苷酸环化酶和一氧化氮合酶抑制剂。
OB 组最大内皮依赖性血管舒张（EDV）值严重降低。exendin-4 处理显著增加了 NO 水平，改善了肥胖组的内皮依赖性血管舒张，并降低了 NF-κB 的表达。在存在特异性抑制剂的情况下，exendin-4 对肥胖大鼠 EDV 的有益作用部分减弱。
exendin-4 可直接改善肥胖大鼠主动脉受损的 EDV。exendin-4 的有益作用似乎部分通过刺激 cAMP/AMPK 相关信号通路和增强内皮型一氧化氮合酶活性来介导。
