Caveolin-1在高盐饮食损伤糖尿病大鼠血管中的作用

目的:观察1型糖尿病(DM)大鼠给予高盐饮食后内皮细胞功能障碍的可能机制。方法:SD大鼠(150~180 g)60只,腹腔注射链唑霉素(70 mg/kg),3 d后空腹血糖≥16.7 mmol/L为1型DM大鼠。正常大鼠和DM大鼠分别给予正常饮食和高盐饮食(8%Na Cl)6周。检测肠系膜动脉舒张功能,Western blot技术检测血管中Akt、内皮型一氧化氮合酶(e NOS)、caveolin-1(Cav-1)等蛋白的水平。结果:高盐饮食DM大鼠收缩压显著高于DM组,其肠系膜动脉乙酰胆碱和胰岛素的舒张作用显著下降(P0.01)。Akt、p-e NOS和NO水平均显著低于DM组(P0.01),Cav-1显著增高(P0.01)。结论:1型糖尿病大鼠高盐饮食血管功能障碍可能与抑制内皮细胞Akt激活及增强Cav-1表达导致的e NOS活性下降有关。

Effect of caveolin-1 expression on high-salt diet-induced endothelial dysfunction in type 1 diabetic rats

AIM: To investigate the underlying mechanisms responsible for endothelial dysfunction of type 1 diabetes mellitus (DM) rats fed with high-salt diet. METHODS: Type 1 DM was induced by intraperitoneal injection of streptozotocin (70 mg/kg). Normal and diabetic rats were fed high-salt food (HS, 8% NaCl) and standard food for 6 weeks, respectively. Isometric tension of the mesenteric arteries were measured. The expression of Akt, endothelial nitric oxide synthase (eNOS) and caveolin-1 (Cav-1) was examined by Western blot. RESULTS: The rats in DM+HS group exhibited more pronounced impairment of vasorelaxation to acetylcholine and insulin compared with either DM group or HS group (P<0.01). Akt and eNOS phosphorylation levels, and nitric oxide (NO) concentration in DM+HS group were significantly lower than those in DM group (P<0.01). The level of Cav-1 in DM+HS group was significantly higher than that in DM group and HS group. CONCLUSION: Impaired endothelial Akt activation, increased Cav-1 expression and resultant decreased eNOS activation contribute to aggravate high-salt diet-induced endothelial dysfunction and hypertension in DM rats.