Cardiology Department, Xidian Group Hospital, Xi'an, People's Republic of China.
Department of Cardiovascular, Gansu Provincial Hospital, Lanzhou, People's Republic of China.
Drug Dev Res. 2019 May;80(3):294-309. doi: 10.1002/ddr.21495. Epub 2019 Mar 12.
This study was designed to delineate the effect of kaempferol (KF) on heart failure (HF) in diabetic rats. Streptozotocin-induced male diabetic rats received KF orally at 10 and 20 mg/kg for 42 consecutive days. In last 2 days of the experimental period, isoproterenol was subcutaneously injected at 85 mg/kg to induce HF. The hearts were processed for hemodynamic, biochemical, molecular, and histological investigations. Systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure were elevated in KF-treated HF-induced diabetic rats. Moreover, KF treatment resulted in decreased fasting blood glucose and glycosylated hemoglobin levels with increased serum insulin levels. Besides, serum cardiac injury markers like troponin-I, creatine kinase-muscle/brain, lactate dehydrogenase, and brain natriuretic peptide levels were significantly reduced in KF treatment. KF treatment has shown decrease in cardiac heme oxygenase-1, nuclear factor erythroid 2-related factor 2 (Nrf-2), and γ-glutamylcysteine synthetase with increased Keap1 mRNA levels. The cardioprotection of KF was improved by inhibition of apoptosis via blocking phosphorylation of Akt/glycogen synthase kinase (GSK)-3β and p38 mitogen-activated protein-kinase/extracellular signal-regulated kinases signaling pathways in HF-induced diabetic rats. Moreover, reduced cardiac apoptosis in KF treatment was confirmed by decreased terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) positive cells, histopathological changes in HF-induced diabetic rats. Therefore, the cardioprotective effect of KF is attributed to the regulation of Nrf2, nuclear factor kappa-light-chain-enhancer of activated B cells, and Akt/GSK-3β signaling pathways in HF-induced diabetic rats.
本研究旨在探讨山奈酚（KF）对糖尿病大鼠心力衰竭（HF）的影响。链脲佐菌素诱导的雄性糖尿病大鼠连续 42 天每天口服 KF 10 和 20mg/kg。在实验期的最后 2 天，皮下注射异丙肾上腺素 85mg/kg 诱导 HF。处理心脏进行血流动力学、生化、分子和组织学研究。KF 治疗 HF 诱导的糖尿病大鼠的收缩压、舒张压和平均动脉压升高。此外，KF 治疗导致空腹血糖和糖化血红蛋白水平降低，血清胰岛素水平升高。此外，血清心脏损伤标志物如肌钙蛋白-I、肌酸激酶-肌肉/脑、乳酸脱氢酶和脑钠肽水平在 KF 治疗中显著降低。KF 治疗显示心脏血红素加氧酶-1、核因子红细胞 2 相关因子 2（Nrf-2）和γ-谷氨酰半胱氨酸合成酶减少，而 Keap1mRNA 水平增加。通过阻断 Akt/糖原合酶激酶（GSK）-3β和 p38 丝裂原活化蛋白激酶/细胞外信号调节激酶信号通路的磷酸化，KF 改善了 HF 诱导的糖尿病大鼠的细胞凋亡，从而发挥其心脏保护作用。此外，KF 治疗中减少的心脏细胞凋亡通过减少末端脱氧核苷酸转移酶 dUTP 缺口末端标记（TUNEL）阳性细胞得到证实，HF 诱导的糖尿病大鼠的组织病理学变化。因此，KF 的心脏保护作用归因于 Nrf2、核因子κB 轻链增强子的激活 B 细胞和 Akt/GSK-3β 信号通路在 HF 诱导的糖尿病大鼠中的调节。
