Astragalus prevents diabetic rats from developing cardiomyopathy by downregulating angiotensin II type2 receptors expression

Abstract

This study examined the potential roles of astragalus and angiotensin II: type 2 receptor (AT2) in rats with streptozotocin (STZ)-induced diabetic cardiomyopathy. Of 52 female 4-weekold Wistar rats treated with high glucose and lipid diet to induce insulin resistance, 7 treated with sodium citrate buffer (pH=4.5) served as controls (con1) and the other 45 were treated by intraperitoncal injection (ip) of STZ to induce type 2 diabetes. After 20 weeks, the maximal velocity decrease of pressure per second in left ventricle within the period of isovolumic relaxation (−dp/dt_max was detected by inserting cannula through right carotid artery. Of the 45 rats, 24 with −dp/dt_max 700 mmHg/s (1 mmHg=0.133 kPa) developing diabetic cardiomyopathy were grouped as follows: 7 treated with double distilled H₂O (ip) were included in control group 2 (con2); other 8 treated with AT2 agonist (CGP42112A, ip) were included in experimental groupl (exp); 9 treated with astragalus (po) constituted experimental group 2 (exp2). All injections lasted 4 weeks (qd) and the heart weight (HW) was recorded. Cardiomyocyte apoptosis index (CAI), mRNA of AT2 and Bel-2 as well as AT2 and Bcl-2 protein values in cardiomyocytes were also measured. Our results showed that −dp/dt_max in expl, exp2 and con2 were much lower than those in con1 (P<0.01). CAI and AT2 in both mRNA and protein in con1 were lower than those in the other three groups (P<0.01). The three parameters above were higher in expl but less in exp2 than those in con2, respectively (P<0.01). The three parameters and HW in expl were much higher than those in exp2 (P<0.01). Changes of Bcl-2 were opposite to those of AT2. Our results suggested that high expression of AT2 might accelerate the apoptosis of cardiomyocytes in diabetic rats and play an important role in precipitating diabetic cardiomyopathy and astragalus protects diabetic rats from developing cardiomyopathy by downregulating AT2.

Keywords

astragalus / diabetic cardiomyopathy / AT2 agonist / apoptosis

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