This study examined if the Fisetin against streptozotocin-induced diabetic cardiomyopathy (DC) in rats involves regulating cardiac metabolism and suppressing protein kinase R (PKR). Male rats were divided (12/groups) as control (non-diabetic), control + Fisetin, T1DM, and T1DM + Fisetin. Fisetin was administered orally at a final dose of 2.5 mg/kg for 12 weeks. In T1DM1-induced rats, Fisetin prevented heart and final body weights loss, lowered circulatory levels troponin I and creatinine kinase-MB (CK-MB), increased fasting insulin levels, and improved ventricular systolic and diastolic functions. It also preserved the structure of the cardiomyocytes and reduced oxidative stress, fibrosis, protein levels of transforming growth factor-β1 (TGF-β1), collagenase 1A, caspase-3, and the activation of JNK, p53, and p38 MAPK. In the control and diabetic rats, Fisetin attenuated fasting hyperglycaemia, the increases in glucose levels after the oral and insulin tolerance tests, and HOMA-IR. It also increased cardiac glucose oxidation by increasing the activity of private dehydrogenase (PDH), phosphofructokinase (PFK), protein levels of PPAR-α and suppressed cardiac inflammation by inhibiting NF-κB. These effects were associated with a reduction in the activity of PKR and subsequent increase in the activity of eeukaryotic initiation factor 2 (eIF2) with a parallel increase in protein levels of p67, a cellular inhibitor of PKR. In cultured cardiomyocytes, Fisetin, prevented high glucose (HG)-induced activation of PKR and reduction in p67, in a dose-dependent manner. However, the effect of Fisetin on PKR was diminished in LG and HG-treated cardiomyocytes with p67-siRNA. In conclusion, Fisetin protects against DC in rats by improving cardiac glucose metabolism and suppressing PKR.

这项研究检查了菲塞汀对大鼠链脲佐菌素诱发的糖尿病性心肌病（DC）是否涉及调节心脏代谢和抑制蛋白激酶R（PKR）。将雄性大鼠分为一组（12只/组）作为对照（非糖尿病），对照+ Fisetin，T1DM和T1DM + Fisetin。Fisetin的最终剂量为2.5 mg / kg口服，持续12周。在T1DM1诱导的大鼠中，Fisetin预防了心脏和最终体重的减轻，降低了肌钙蛋白I和肌酐激酶-MB（CK-MB）的循环水平，提高了空腹胰岛素水平，并改善了心室收缩和舒张功能。它还保留了心肌细胞的结构，并降低了氧化应激，纤维化，转化生长因子-β1（TGF-β1），胶原酶1A，胱天蛋白酶-3的蛋白质水平以及JNK，p53和p38 MAPK的活化。在对照组和糖尿病大鼠中，Fisetin减轻了空腹高血糖症，口服和胰岛素耐受性测试后糖水平升高以及HOMA-IR。它还通过增加私人脱氢酶（PDH），磷酸果糖激酶（PFK）的活性，PPAR-α的蛋白质水平来增加心脏葡萄糖氧化，并通过抑制NF-κB来抑制心脏炎症。这些作用与PKR活性的降低和随后的真核生物起始因子2（eIF2）活性的增加相关，同时PKR的细胞抑制剂p67的蛋白质水平也平行升高。在培养的心肌细胞中，Fisetin以剂量依赖的方式阻止了高葡萄糖（HG）诱导的PKR激活和p67的降低。然而，在使用p67-siRNA的LG和HG处理的心肌细胞中，Fisetin对PKR的作用减弱了。