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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 nFGF1 on aortic vascular function in type 2 diabetic rats induced by streptozotocin and high-fat diet and to explore its mechanism. Methods: Thirty male SD rats (5 ± 20 g), 5 weeks old, were randomly divided into normal control group, type 2 diabetes mellitus group and type 2 diabetes mellitus + n FGF1 administration group, with 10 rats in each group. The treatment group was given intraperitoneal injection of 0.5 mg / kg n FGF1 for 4 weeks (administered on alternate days) while the control group and the diabetic model group received the same amount of saline. The changes of blood glucose in each group were observed, the changes of aortic diastolic function were detected, the level of superoxide dismutase (SOD) in arterial tissue was detected, the expression of cyclooxygenase 2 (COX-2), phosphorylated extracellular signal regulated (P-ERK) and endothelial nitric oxide synthase (eNOS) were detected by enzyme-linked immunosorbent assay (ELISA). The level of glucose, cholesterol and triglyceride in serum was detected to study the regulation of nFGF1 on aortic vascular function in type 2 diabetic rats effect. Results: n FGF1 significantly decreased serum glucose, cholesterol and triglyceride levels, significantly increased aortic SOD activity and eNOS protein expression, and significantly decreased the protein levels of COX-2 and p-ERK in type 2 diabetic rats. CONCLUSION: n FGF1 can effectively protect aortic vascular function in type 2 diabetic rats. The mechanism may be related to lowering blood glucose and blood lipid, reducing inflammation and oxidative stress, and up-regulating eNOS signaling pathway.