Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092, P.R. China.
Department of Pathophysiology, Anqing Medical College, Anqing, Anhui 246052, P.R. China.
Mol Med Rep. 2018 Aug;18(2):2300-2306. doi: 10.3892/mmr.2018.9192. Epub 2018 Jun 19.
To explore the effects of captopril on calpain‑mediated apoptosis of myocardial cells and cardiac function in diabetic rats, 30 adult male Sprague‑Dawley rats were randomly divided into three groups: Negative control (NC group), untreated diabetic rats (DM group) and diabetic rats treated with captopril (Cap group). Diabetes was induced by streptozotocin injection. Captopril was intragastrically administered at a daily dose of 50 mg/kg for 12 weeks; the NC and DM groups received an equivalent volume of saline. After 12 weeks of treatment, left ventricular systolic pressure (LVSP), left ventricular end‑diastolic pressure (LVDEP), maximal rate of left ventricular pressure increase (+dp/dtmax), maximal rate of left ventricular pressure decrease (‑dp/dtmax) and left ventricular mass index (LVMI) were measured. The levels of calpain‑1, calpain‑2, B‑cell lymphoma (Bcl)‑2, Bcl‑2 associated protein X (Bax) and total caspase‑3 were detected in cardiac tissue by western blot analysis. The apoptotic index (AI) was assessed with a terminal deoxynucleotidyl transferase‑mediated dUTP nick‑end labeling assay. The ultrastructure of cardiac tissue was determined by transmission electron microscopy. Compared with the NC group, LVDEP and LVMI were increased, whereas LVSP, +dp/dtmax and ‑dp/dtmax were decreased in the DM group. In the Cap group, LVDEP and LVMI were decreased, whereas LVSP, +dp/dtmax and ‑dp/dtmax were increased compared with the DM group. Bcl‑2 protein expression was decreased, whereas the levels of calpain‑1, calpain‑2, Bax and total caspase‑3 protein were increased in the DM group, compared with the NC group. Cap treatment increased Bcl‑2 protein expression and decreased calpain‑1, calpain‑2, Bax and total caspase‑3 protein expression compared with the DM group. Additionally, the AI was increased in the DM group compared with the NC group, and decreased in the Cap group compared with the DM group. Furthermore, ultrastructural examination demonstrated that myocardial cell injury was reduced in the Cap group compared with the DM group. Therefore, captopril improved myocardial structure and ventricular function, by inhibiting calpain‑1 and calpain‑2 activation, increasing Bcl‑2 expression, reducing Bax expression and subsequently inhibiting caspase‑3‑dependent apoptosis.
为了探讨卡托普利对糖尿病大鼠心肌细胞钙蛋白酶介导的细胞凋亡及心功能的影响，将 30 只成年雄性 Sprague-Dawley 大鼠随机分为三组：阴性对照组（NC 组）、未治疗的糖尿病大鼠（DM 组）和接受卡托普利治疗的糖尿病大鼠（Cap 组）。采用链脲佐菌素注射诱导糖尿病。Cap 组每日灌胃给予卡托普利 50mg/kg，连续 12 周；NC 组和 DM 组给予等体积生理盐水。治疗 12 周后，测量左心室收缩压（LVSP）、左心室舒张末期压（LVDEP）、左心室压力最大上升速率（+dp/dtmax）、左心室压力最大下降速率（-dp/dtmax）和左心室质量指数（LVMI）。采用 Western blot 分析检测心肌组织中钙蛋白酶-1、钙蛋白酶-2、B 细胞淋巴瘤（Bcl）-2、Bcl-2 相关蛋白 X（Bax）和总半胱氨酸天冬氨酸蛋白酶-3 的水平。采用末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记法评估细胞凋亡指数（AI）。采用透射电子显微镜观察心肌组织的超微结构。与 NC 组相比，DM 组 LVDEP 和 LVMI 增加，而 LVSP、+dp/dtmax 和 -dp/dtmax 降低。与 DM 组相比，Cap 组 LVDEP 和 LVMI 降低，而 LVSP、+dp/dtmax 和 -dp/dtmax 升高。与 NC 组相比，DM 组 Bcl-2 蛋白表达降低，而钙蛋白酶-1、钙蛋白酶-2、Bax 和总半胱氨酸天冬氨酸蛋白酶-3 蛋白水平升高。与 DM 组相比，Cap 治疗组 Bcl-2 蛋白表达增加，钙蛋白酶-1、钙蛋白酶-2、Bax 和总半胱氨酸天冬氨酸蛋白酶-3 蛋白表达降低。此外，与 NC 组相比，DM 组 AI 增加，与 DM 组相比，Cap 组 AI 降低。此外，超微结构检查显示，与 DM 组相比，Cap 组心肌细胞损伤减少。因此，卡托普利通过抑制钙蛋白酶-1 和钙蛋白酶-2 的激活、增加 Bcl-2 表达、减少 Bax 表达，从而抑制 caspase-3 依赖性细胞凋亡，改善心肌结构和心室功能。
