Department of Pathophysiology, Harbin Medical University, Harbin 150086, China.
Diabetes Res Clin Pract. 2012 Mar;95(3):378-85. doi: 10.1016/j.diabres.2011.11.007. Epub 2011 Dec 3.
To observe the dynamic expression of calcium-sensing receptor (CaSR) in myocardium of diabetic rats and explore its role in diabetic cardiomyopathy (DCM), 40 male Wistar rats were randomly divided into 4 groups including control, diabetic-4 weeks, diabetic-8 weeks and spermine treatment groups (240 μM of spermine in drinking water). The type 2 Diabetes mellitus (DM) models were established by intraperitoneal injection of streptozotocin (STZ, 30 mg/kg) after high-fat and high-sugar diet for one month. The echocardiographic parameters were measured, cardiac morphology was observed by electron microscope and HE staining. The intracellular calcium concentration (Ca(2+)) was detected by laser-scanning confocal microscope. Western blot analyzed the expression of CaSR, protein kinase C α(PKC-α) and calcium handling regulators, such as phospholamban (PLN), Ca(2+)-ATPase (SERCA), and ryanodine receptor (RyR). Compared with control group, Ca(2+) and the expression of CaSR, RyR and SERCA/PLN were decreased, while PKC-α and PLN were significantly increased in a time-dependent manner in diabetic groups. Meanwhile diabetic rats displayed abnormal cardiac structure and systolic and diastolic dysfunction, and spermine (CaSR agonist) could prevent or slow its progression. These results indicate that the CaSR expression of myocardium is reduced in the progress of DCM, and its potential mechanism is related to the impaired intracellular calcium homeostasis.
观察钙敏感受体（CaSR）在糖尿病大鼠心肌中的动态表达，探讨其在糖尿病心肌病（DCM）中的作用，将 40 只雄性 Wistar 大鼠随机分为 4 组，分别为对照组、糖尿病 4 周组、糖尿病 8 周组和亚精胺治疗组（饮用水中含 240 μM 亚精胺）。糖尿病 2 型（DM）模型通过高脂高糖饮食 1 个月后腹腔注射链脲佐菌素（STZ，30 mg/kg）建立。测量超声心动图参数，电镜观察心脏形态，HE 染色。激光共聚焦显微镜检测细胞内钙离子浓度(Ca(2+))。Western blot 分析 CaSR、蛋白激酶 C α（PKC-α）和钙处理调节剂的表达，如肌浆网磷蛋白（PLN）、Ca(2+)-ATP 酶（SERCA）和兰尼碱受体（RyR）。与对照组相比，糖尿病组 Ca(2+)和 CaSR、RyR 和 SERCA/PLN 的表达呈时间依赖性降低，而 PKC-α 和 PLN 显著增加。同时，糖尿病大鼠表现出心脏结构异常和收缩及舒张功能障碍，而亚精胺（CaSR 激动剂）可预防或延缓其进展。这些结果表明，在 DCM 进展过程中心肌 CaSR 的表达减少，其潜在机制与细胞内钙稳态受损有关。
