Lin Xuefeng, Wu Min, Liu Bo, Wang Junkui, Guan Gongchang, Ma Aiqun, Zhang Yong
Department of Cardiovascular Medicine, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Department of Endocrinology, Shaanxi Provincial People's Hospital, Third Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710068, P.R. China.
Mol Med Rep. 2015 Dec;12(6):8193-200. doi: 10.3892/mmr.2015.4432. Epub 2015 Oct 13.
Candesartan, an angiotensin II type 1 receptor antagonist, has a variety of biological activities, including antioxidant, anti‑inflammatory and anticancer activities, with specific pharmacological effects. The present study investigated the mechanisms and protective effect of candesartan on acute myocardial infarction in rats. Male Wistar rats (8‑week‑old) were induced as a model of acute myocardial infarction and treated with candesartan (0.25 mg/kg) for 2 weeks. The present study first measured the activities of casein kinase (CK), the MB isoenzyme of creatine kinase (CK‑MB) and lactate dehydrogenase (LDH), the level of cardiac troponin T (cTnT) and infarct size. Subsequently, western blot analysis was performed to analyze the protein expression levels of inducible nitric oxide synthase (iNOS) and heat shock protein 72 (HSP72) in the rats. An enzyme linked immunosorbent assay was used to detect iNOS and nuclear factor‑κB (NF‑κB) activity. In addition, gene expression levels of monocyte chemotactic protein‑1 (MCP‑1) and activating protein‑1 (AP‑1) were determined using reverse transcription‑quantitative polymerase chain reaction analysis. Finally, the activities of caspase‑3 and caspase‑9 were examined using colorimetric assay kits. In the serum of the rat model of acute myocardial infarction, candesartan significantly increased the activities of CK, CK‑MB and LDH, and the level of cTnT. The infarction size was perfected by candesartan treatment. Candesartan significantly reduced the protein expression and activity of iNOS, the activity of NF‑κB p65, and the gene expression levels of MCP‑1 and AP‑1 in the rat model of acute myocardial infarction. Candesartan increased the protein expression of HSP‑72 in the acute myocardial infarction rat model. However, candesartan did not effect the levels of caspase‑3 or caspase‑9 in the rat model of acute myocardial infarction. These results suggested that candesartan ameliorates acute myocardial infarction in rats through iNOS, NF‑κB, MCP‑1 and AP‑1, and the restoration of HSP72.
坎地沙坦是一种血管紧张素II 1型受体拮抗剂，具有多种生物活性，包括抗氧化、抗炎和抗癌活性，具有特定的药理作用。本研究探讨了坎地沙坦对大鼠急性心肌梗死的作用机制及保护作用。将8周龄雄性Wistar大鼠诱导为急性心肌梗死模型，并用坎地沙坦（0.25mg/kg）治疗2周。本研究首先测定了酪蛋白激酶（CK）、肌酸激酶MB同工酶（CK-MB）和乳酸脱氢酶（LDH）的活性、心肌肌钙蛋白T（cTnT）水平和梗死面积。随后，进行蛋白质印迹分析以分析大鼠中诱导型一氧化氮合酶（iNOS）和热休克蛋白72（HSP72）的蛋白表达水平。采用酶联免疫吸附测定法检测iNOS和核因子-κB（NF-κB）活性。此外，使用逆转录-定量聚合酶链反应分析测定单核细胞趋化蛋白-1（MCP-1）和活化蛋白-1（AP-1）的基因表达水平。最后，使用比色测定试剂盒检测caspase-3和caspase-9的活性。在急性心肌梗死大鼠模型的血清中，坎地沙坦显著增加了CK、CK-MB和LDH的活性以及cTnT水平。坎地沙坦治疗改善了梗死面积。坎地沙坦显著降低了急性心肌梗死大鼠模型中iNOS的蛋白表达和活性、NF-κB p65的活性以及MCP-1和AP-1的基因表达水平。坎地沙坦增加了急性心肌梗死大鼠模型中HSP-72的蛋白表达。然而，坎地沙坦对急性心肌梗死大鼠模型中caspase-3或caspase-9的水平没有影响。这些结果表明，坎地沙坦通过iNOS、NF-κB、MCP-1和AP-1以及HSP72的恢复改善大鼠急性心肌梗死。
