Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
J Diabetes Res. 2018 Feb 28;2018:1067853. doi: 10.1155/2018/1067853. eCollection 2018.
Although statins have been suggested to attenuate the progression of diabetic cardiomyopathy, its effect without glycemic control remains unclear. Therefore, we evaluated the effect of pravastatin on diabetic rat hearts according to glycemic control. Rats were randomly divided into five groups: control (C), diabetes (D), diabetes with insulin (I), diabetes with pravastatin (P), and diabetes with insulin and pravastatin (IP). Eight weeks after allocated treatments, the heart was extracted and analyzed following echocardiography. Cardiac fibrosis was measured using Masson's trichrome stain. Cardiac expression of collagen I/III, matrix metalloproteinase (MMP)-2, MMP-9, and angiotensin-converting enzyme (ACE)/ACE2 was evaluated by immunohistochemistry and/or Western blot. Enzyme-linked immunosorbent assay was used for measuring reactive oxygen species (ROS). Diabetic groups without glycemic control (D and P) showed significantly impaired diastolic function and increased levels of cardiac fibrosis, collagen I/III, MMP-2, MMP-9, and ROS production. However, there were little significant differences in the outcomes among the control and two glucose-controlled diabetic groups (I and IP). Groups C and IP showed more preserved ACE2 and lower ACE expressions than the other groups did (D, I, and P). Our study suggested glycemic control would be more important to attenuate the progression of diabetic cardiomyopathy than pravastatin medication.
虽然他汀类药物被认为可以减轻糖尿病心肌病的进展，但在没有血糖控制的情况下其效果尚不清楚。因此，我们根据血糖控制情况评估了普伐他汀对糖尿病大鼠心脏的作用。大鼠被随机分为五组：对照组（C）、糖尿病组（D）、糖尿病胰岛素组（I）、糖尿病普伐他汀组（P）和糖尿病胰岛素普伐他汀组（IP）。分配治疗 8 周后，提取心脏并进行超声心动图分析。用 Masson 三色染色法测量心脏纤维化。通过免疫组织化学和/或 Western blot 评估心脏胶原 I/III、基质金属蛋白酶（MMP）-2、MMP-9 和血管紧张素转换酶（ACE）/ACE2 的表达。酶联免疫吸附试验用于测量活性氧（ROS）。未进行血糖控制的糖尿病组（D 和 P）舒张功能明显受损，心脏纤维化、胶原 I/III、MMP-2、MMP-9 和 ROS 生成水平升高。然而，在控制组和两个血糖控制的糖尿病组（I 和 IP）之间，结果几乎没有显著差异。与其他组（D、I 和 P）相比，C 组和 IP 组 ACE2 的表达更稳定，ACE 的表达更低。我们的研究表明，血糖控制对于减轻糖尿病心肌病的进展比普伐他汀药物更重要。
