Department of Geriatrics, Huashan Hospital, Fudan University School of Medicine, Shanghai 200040, China.
J Diabetes Complications. 2010 May-Jun;24(3):199-208. doi: 10.1016/j.jdiacomp.2008.12.003. Epub 2009 Feb 20.
Diabetic cardiomyopathy is associated with high morbidity and mortality of heart failure. Overactivation of the local chymase-Ang II system plays a dominant role in diabetic cardiomyopathy. Astragalus polysaccharide (APS) is used in traditional Chinese medicine to boost immunity. To study the effect of APS on local system of chymase-Ang II in diabetic cardiomyopathy, we investigated APS/normal saline (NS)-administrated streptozotocin-induced diabetic hamsters. After APS/NS administration at a dose of 1 g/kg per day for 10 weeks, hemodynamic parameters, levels of insulin (INS), C-peptide (C-P), glycosylated serum protein (GSP), lipoproteins, myocardial enzymes, and Ang II (plasma and myocardial) were tested; myocardial collagen (type I and III), myocardial ultrastructure, and activities of matrix metalloproteinase (MMPs) were measured; activities and expression of cardiac chymase and ACE were detected by using quantitative real-time RT-PCR and RIA; protein expression of cardiac phosphoric extracellular signal-regulated kinase 1/2 (p-ERK1/2) was measured by Western blot. AP-administrated diabetic hamsters had lower levels of GSP, lipoproteins, myocardial enzymes, myocardial Ang II, expression of collagen I and I/ III, activities of pro-MMP-2 and MMP-2, activities and expression of chymase, and expression of p-ERK1/2 than NS-administrated diabetic hamsters and could better protect the myocardial ultrastructure. There was no difference in hemodynamic parameters between two groups. These results indicate that APS could inhibit diabetic cardiomyopathy in hamsters depending on the suppression of the local cardiac chymase-Ang II system.
糖尿病心肌病与心力衰竭的高发病率和死亡率有关。局部糜酶 - 血管紧张素 II 系统的过度激活在糖尿病心肌病中起主导作用。黄芪多糖（APS）在传统中药中被用于增强免疫力。为了研究 APS 对糖尿病心肌病中局部糜酶 - 血管紧张素 II 系统的影响，我们研究了 APS/生理盐水（NS）治疗的链脲佐菌素诱导的糖尿病仓鼠。APS/NS 以 1 g/kg/天的剂量给药 10 周后，测试了血流动力学参数、胰岛素（INS）、C 肽（C-P）、糖化血清蛋白（GSP）、脂蛋白、心肌酶和血管紧张素 II（血浆和心肌）水平；测量了心肌胶原（I 型和 III 型）、心肌超微结构和基质金属蛋白酶（MMPs）的活性；通过定量实时 RT-PCR 和 RIA 检测心脏糜酶和 ACE 的活性和表达；通过 Western blot 测量心脏磷酸细胞外信号调节激酶 1/2（p-ERK1/2）的蛋白表达。APS 治疗的糖尿病仓鼠的 GSP、脂蛋白、心肌酶、心肌血管紧张素 II、胶原 I 和 I/III 的表达、前 MMP-2 和 MMP-2 的活性、糜酶的活性和表达以及 p-ERK1/2 的表达均低于 NS 治疗的糖尿病仓鼠，并且可以更好地保护心肌超微结构。两组之间的血流动力学参数没有差异。这些结果表明，APS 可通过抑制局部心脏糜酶 - 血管紧张素 II 系统抑制糖尿病心肌病。
