同型半胱氨酸对孕鼠糖代谢的影响与机制分析

Effect and Mechanism of Homocysteine on Glucose Metabolism in Pregnant Rats

目的:探讨同型半胱氨酸(homocysteine,HCY)摄入后对孕鼠糖代谢的影响以及生物学机制分析。方法:孕鼠妊娠10 d后,将实验动物随机分为3组,每组12只,妊娠对照组(Ctrl)腹腔注射生理盐水,同型半胱氨酸高剂量组(HCYH)和同型半胱氨酸低剂量组(HCYL)腹腔注射HCY溶液,注射浓度分别为200 mg/kg·d和100 mg/kg·d,持续20 d(即为HCY20 d)后,利用血糖含量检测试剂盒和胰岛素试剂盒分别检测孕鼠空腹血糖水平、胰岛素水平;葡萄糖检测试剂盒对孕鼠葡萄糖耐量和胰岛素抵抗进行检测;蛋白免疫印迹法检测孕鼠目的蛋白过氧化物酶体增殖物激活受体γ(PPARγ)、葡萄糖转运蛋白4(GLUT4)、蛋白激酶B(AKT)、磷酸化AKT蛋白(P-AKT)的表达。结果:与Ctrl组比较,在孕鼠注射HCY后,空腹血糖水平升高、血清中胰岛素浓度下降、HOMA-β指数下降、HOMA-IR指数升高(P<0.05);摄入葡萄糖后,孕鼠血糖随时间的变化而下降,葡萄糖曲线下面积升高(P<0.05);摄入胰岛素后,孕鼠血糖随时间的变化而升高,胰岛素曲线下面积升高(P<0.05);PPARγ、P-AKT、GLUT4蛋白表达水平下降,HCYH组降低水平更为显著(P<0.05)。结论:孕鼠HCY摄入后,生物体糖代谢紊乱,AKT磷酸化表达水平抑制,HCY可能通过降低PPARγ的表达减少AKT磷酸化,导致胰岛素受体的活化,进而激活了PI3K/AKT通路,减少了脂肪组织中的GLUT4表达,增加了对于葡萄糖的摄取能力。

Objective: To investigate the effect of homocysteine(HCY) intake on glucose metabolism in pregnant rats and analysis of its biological mechanism. Methods: After 10 days of pregnancy, pregnant rats were randomly divided into 3 groups, 12 animals in each group. The pregnant control group(Ctrl) was intraperitoneally injected with saline;the homocysteine high-dose group(HCYH) and the homocysteine low-dose group(HCYL) were intraperitoneally injected with HCY solution at a concentration of 200 mg/kg·d and 100 mg/kg·d respectively for 20 d(HCY20 d), and then. fasting blood glucose levels and insulin levels in pregnant rats were tested with blood glucose content detection kit and insulin kit, respectively;the glucose tolerance and insulin resistance in pregnant rats were detected with glucose detection kit. target protein peroxisome proliferator-activated receptor gamma(PPARγ) in pregnant mice, Glucose transporter(GLUT4), protein kinase B(AKT), and phosphorylated AKT protein(P-AKT) expression were detected with Western blotting. Results:Compared with the Ctrl group, after injection of HCY in pregnant rats, the fasting blood glucose level increased, the serum insulin concentration decreased, the HOMA-β index decreased, the HOMA-IR index increased(P<0.05). After glucose intake, the blood glucose of pregnant rats decreases with time, and the area under the glucose curve increased(P <0.05). After insulin intake, blood glucose of pregnant mice increases with time The area under the insulin curve increased(P <0.05). PPARγ, P-AKT, GLUT4 protein expression levels were reduced, especially PPARγ expression levels, HCYH group significantly changed(P<0.05). Conclusion: After ingestion of HCY in pregnant rats, the body’s glucose metabolism is disordered and the expression level of AKT phosphorylation is inhibited. HCY may reduce AKT phosphorylation by reducing the expression of PPARγ, lead to the activation of insulin receptors, activate the PI3 K/AKT pathway, reduce the expression of GLUT4 in adipose tissue and increase the organism’s ability to take up glucose.