成纤维细胞生长因子1非促分裂突变体对2型糖尿病大鼠血管功能的保护作用  

Alleviation of aortic vascular dysfunction in STZ/HFD-induced type 2 diabetic rats by nFGF1

作　　者：南燕[1] 李娜[2] 董育[2] 邱鹏程 胡智盛 蔡昌洲 孔灵国 何正乐 应磊 汪洋[2] 

机构地区：[1]温州医科大学附属第二医院育英儿童医院新生儿科,浙江温州325027 [2]温州医科大学病理生理学教研室,浙江温州325035

出　　处：《中国病理生理杂志》2017年第11期1945-1950,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81400273);浙江省自然科学基金资助项目(No.LQ13H020006);温州市科技局公益技术研究医学项目(No.Y20140660);温州市科技局公益技术研究医学项目(No.Y20160097)

摘　　要：目的:研究成纤维细胞生长因子1非促分裂突变体(n FGF1)对链脲佐菌素和高脂饮食诱导的2型糖尿病大鼠主动脉血管功能的保护作用并探讨其机制。方法:将5周龄左右(200±20)g雄性SD大鼠30只随机分为正常对照组、2型糖尿病模型组和2型糖尿病模型+n FGF1给药组,每组10只。给药组予以0.5 mg/kg n FGF1腹腔注射4周(隔天给药),对照组和糖尿病模型组则给予等量的生理盐水。监测各组大鼠的血糖变化情况,检测大鼠主动脉舒张功能变化,检测动脉组织超氧化物歧化酶(SOD)水平,检测环氧化酶2(COX-2)、磷酸化细胞外信号调节激酶(p-ERK)和内皮型一氧化氮合酶(e NOS)的蛋白表达水平,检测血清中葡萄糖、胆固醇和甘油三酯水平,研究n FGF1对2型糖尿病大鼠主动脉血管功能的调节作用。结果:n FGF1可明显降低2型糖尿病大鼠血清中葡萄糖、胆固醇和甘油三酯水平,显著增强主动脉SOD活性及e NOS蛋白表达水平,并明显下调COX-2和p-ERK的蛋白水平。结论:n FGF1可以有效保护2型糖尿病大鼠主动脉血管功能,其机制可能与降低血糖和血脂,减轻炎症和氧化应激反应,以及上调e NOS信号通路有关。AIM：To investigate the protective effect of non-mitogenic fibroblast growth factor 1（n FGF1） on the aortic vascular function in streptozotocin（STZ）/high-fat diet（HFD）-induced type 2 diabetic rats and its underlying mechanisms.METHODS：Five-week-old male SD rats（n = 30） were randomly divided into 3 groups（n = 10 in each group）,including normal control group,type 2 diabetic group and n FGF1 treatment group（type 2 diabetic rats were intraperitoneally injected with 0.5 mg/kg n FGF1 every other day for 4 weeks）.After the rats were sacrificed,blood glucose,cholesterol and triglyceride levels,aorta diastolic function and superoxide dismutase（SOD） level in the aorta of each group were measured.Besides,the protein levels of cyclooxygenase-2（COX-2）,phosphorylated extracellular signal-regulated kinase（p-ERK） and endothelial nitric oxide synthase（e NOS） in the aorta were determined by Western blot.RESULTS：n FGF1 markedly lowered blood glucose,cholesterol and triglyceride levels,enhanced aorta SOD activity and upregulated protein level of e NOS in the type 2 diabetic rats.Furthermore,the increased protein levels of COX-2 and p-ERK in the type2 diabetic rats were largely abrogated by n FGF1.CONCLUSION：n FGF1 effectively attenuates aortic vascular dysfunction in the type 2 diabetic rats,which may be associated with decreasing blood glucose,cholesterol and triglyceride levels,reducing inflammation and oxidative stress response,and activating e NOS signaling pathway.

关 键 词：2型糖尿病 成纤维细胞生长因子1 炎症 氧化应激 

分 类 号：R587.1[医药卫生—内分泌] R363[医药卫生—内科学]