目的 探讨厄贝沙坦对高血压合并2型糖尿病（T2DM）大鼠胰岛素抵抗的影响及其作用。 方法 自发性高血压大鼠（SHR）采用高糖高脂饮食联合链脲佐菌素（STZ）建立T2DM模型，随机分为模型组、厄贝沙坦低、高剂量组。以正常大鼠作为对照组。厄贝沙坦低、高剂量组每日分别按30、60 mg/kg剂量灌服厄贝沙坦，对照组和模型组灌服等量生理盐水。测量大鼠收缩压（SBP）、空腹血糖（FBG）、胰岛素抵抗模型评估指数（HOMA-IR）、胰岛素受体底物-1（IRS-1）、磷脂酰肌醇（-3）激酶p85亚基（PI3Kp85）、蛋白激酶B（AKT）、磷酸化蛋白（p-AKT）及葡萄糖转运蛋白4（GLUT4）的表达。 结果 与对照组相比，模型组SBP、FBG、FINS和HOMA-IR升高（P<0.05），IRS-1、PI3Kp85、p-AKT和GLUT4降低（P<0.05）；与模型组相比，厄贝沙坦低、高剂量上述指标均发生逆转（P<0.05）。 结论 厄贝沙坦可通过IRS-1/PI3K/GLUT4信号通路改善高血压合并T2DM大鼠胰岛素抵抗。
Abstract
Objective To investigate the effect of irbesartan on insulin resistance in hypertensive rats with type 2 diabetes mellitus (T2DM). Methods Spontaneously hypertensive rats (SHR) were randomly divided into a model group, an irbesartan low dose group and an irbesartan high dose group. Normal rats were used as control group. Irbesartan was administered daily at 30 and 60 mg/kg in the low and high dose groups, while the same amount of normal saline was performed in the control group and model group. Systolic blood pressure (SBP), fasting blood glucose (FBG), insulin resistance model evaluation index (HOMA-IR), insulin receptor substrate -1 (IRS-1), phosphatidylinositol (-3) kinase P85 subunit (PI3Kp85), protein kinase B (AKT), phosphorylated protein (p-AKT), and glucose transporter 4 (GLUT4) were measured in rats. Results Compared with the control group, SBP, FBG, FINS and HOMA-IR in the model group significantly increased (P<0.05), while IRS-1, PI3Kp85, P-Akt and GLUT4 significantly decreased (P<0.05). Compared with the model group, the above indicators were reversed in both the low and high dose irbesartan groups(P<0.05). Conclusions Irbesartan can improve insulin resistance in T2DM rats with hypertension through IRS-1/PI3K/GLUT4 signaling pathway.
关键词
厄贝沙坦 /
高血压 /
2型糖尿病 /
胰岛素抵抗 /
IRS-1/PI3K/GLUT4信号通路
Key words
Irbesartan /
High blood pressure; /
/
Type 2 diabetes; /
/
Insulin resistance; /
/
IRS-1/PI3K/GLUT4 signaling pathway
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