抑制糖尿病大鼠PI3K/Akt信号通路对其氧化应激水平及血管内皮生长因子的影响

Effect of inhibiting PI3K/Akt signaling pathway on oxidative stress level and vascular endothelial growth factor in diabetic rats

目的探讨抑制糖尿病大鼠磷脂酰肌醇-3-激酶/蛋白激酶B(PI3K/Akt)信号通路对其氧化应激水平及血管内皮生长因子(VEGF)的影响。方法36只雄性SPF级SD大鼠按照随机数字表法平分为3组:正常组、模型组与LY294002组。模型组与LY294002组均建立糖尿病大鼠模型,然后分别给予5%二甲基亚砜与溶于5%二甲基亚砜中的LY2940023 mg/kg治疗,正常组不进行建模,在相同时间内给予5%二甲基亚砜溶液治疗。3组连续给药7 d。记录大鼠摄食量、饮水量、尿量、体重、血糖以及超氧化物歧化酶、丙二醛含量、VEGF表达变化情况。结果所有大鼠都未出现死亡情况。模型组与LY294002组大鼠的摄食量、饮水量、尿量均高于正常组,体重低于正常组,差异均有统计学意义(P<0.05),LY294002组大鼠的摄食量、饮水量、尿量均低于模型组,体重高于模型组,差异均有统计学意义(P<0.05)。模型组大鼠的血糖高于正常组,LY294002组大鼠血糖低于模型组,差异均有统计学意义(P<0.05)。模型组与LY294002组大鼠的血清超氧化物歧化酶含量低于正常组,丙二醛含量和肝脏VEGF、PI3K蛋白相对表达水平高于正常组,差异均有统计学意义(P<0.05);LY294002组大鼠的血清超氧化物歧化酶含量高于模型组,丙二醛含量和肝脏VEGF、PI3K蛋白相对表达水平低于模型组,差异均有统计学意义(P<0.05)。结论抑制PI3K/Akt信号通路的激活可改善糖尿病大鼠氧化应激反应水平,并抑制VEGF的表达,从而可改善大鼠的糖尿病症状与降低血糖水平。

Objective To investigate the effect of inhibiting phosphatidylinositol-3-kinase/protein kinase B(PI3K/Akt)signaling pathway in diabetic rats on the level of oxidative stress and vascular endothelial growth factor(VEGF).Methods A total of 36 cases of male SPF SD rats were divided into three groups-normal group,model group and LY294002 group according to the random number table method.Both the model group and the LY294002 group established diabetic rat models,and then were treated with 5%dimethyl sulfoxide and LY2940023 mg/kg dissolved in 5%dimethyl sulfoxide.The normal group were not modeled and were given 5%dimethyl sulfoxide solution at the same time.The three groups were given continuous treatment for 7 days,and the rats'hypoxia and VEGF expression changes were recorded.Results None of the rats died.The food intake,water intake,and urine output of the model group and LY294002 group were higher than those of the normal group,and their body weight was lower than that of the normal group,the differences were statistically significant(P<0.05).The food intake,water intake,and urine output of the rats in the LY294002 group were lower than those of the model group,and the body weight was higher than that of the model group,the differences were statistically significant(P<0.05).The blood glucose of rats in the model group was higher than that of the normal group,the blood glucose in the LY294002 group was lower than that of the model group,and the differences were statistically significant(P<0.05).The serum superoxide dismutase content of rats in the model group and LY294002 group was lower than that of the normal group,and the levels of malondialdehyde and the relative expression levels of liver VEGF and PI3K proteins were higher than those of the normal group,the differences were statistically significant(P<0.05);The serum superoxide dismutase content of rats in the LY294002 group was higher than that of the model group,and the malondialdehyde content and the relative expression levels of liver VEGF and PI3K proteins were lower than that of the model group,the differences were statistically significant(P<0.05).Conclusion Inhibiting the activation of PI3K/Akt signaling pathway can improve the level of oxidative stress in diabetic rats and inhibit the expression of VEGF,thereby improving the symptoms of rats and lowering blood sugar levels.