Guo Xinhong, Cao Wenjiang, Yao Jiaming, Yuan Yong, Hong Ye, Wang Xinchun, Xing Jianguo
Department of Pharmacy, First Affiliated Hospital of the Medical College, Shihezi University, Shihezi, Xinjiang 832000, P.R. China.
Xinjiang Institute of Materia Medica, Ürümqi, Xinjiang 830004, P.R. China.
Mol Med Rep. 2015 Mar;11(3):2227-33. doi: 10.3892/mmr.2014.2954. Epub 2014 Nov 14.
Tilianin, the main effective flavonoid monomer enriched from Dracocephalum moldavuca L., has been shown to have cardioprotective effects. However, the mechanism of tilianin cardioprotection remains largely unknown. The present study aimed to investigate the effects of tilianin preconditioning on myocardial ischemia/reperfusion injury and to analyze the possible mechanism of action. A total of 48 male Sprague Dawley rats were randomized into sham, model myocardial ischemia/reperfusion injury (MI/RI), propranolol hydrochloride positive control, and high‑, medium‑ and low‑dose tilianin groups (n=8 each). The rats in the tilianin groups were perfused with either 1.5, 2.5 or 5.0 mg/kg/d tilianin a week prior to surgery. The positive control group were perfused with 25 mg/kg/d propranolol. Saline was administered to the sham surgery and the MI/RI groups. The MI/RI model was established by ligating the left anterior descending coronary artery for 30 min, which was subsequently removed and the mice were observed for 120 min prior to sacrifice. Na+‑K+‑ATPase, Ca2+‑ATPase, nitric oxide (NO), nitric oxide synthase (NOS) and endothelial system‑related factors were analyzed using the respective detection kits. Immunohistochemistry was used to determine the expression levels of Bcl‑2 and Bax. Caspase‑3 activity was measured by quantitative polymerase chain reaction. The results showed that tilianin preconditioning significantly increased ATPase activity (P<0.01 and P<0.05) as compared with the model group. With regards to the regulation of endothelial function, significant decreases (P<0.01 and P<0.05) were detected in the serum NO levels and myocardial NOS activity when tilianin was administered to MI/RI rats, as compared with the model group, . In addition, the tilianin drug groups exhibited dose‑dependent reductions in the serum levels of endothelin 1 and thromboxane B2, and increases in the serum levels of calcitonin gene‑related peptide and 6‑keto prostaglandin F1a as compared with the model group (P<0.01 and P<0.05). Notably, the administration of tilianin significantly inhibited apoptosis, as evidenced by an increase in Bcl‑2 expression, and reductions in Bax and caspase‑3 mRNA expression levels (P<0.01 and P<0.05). These data indicate that pretreatment with tilianin exerts potent cardioprotective effects in rats with MI/RI. The anti‑MI/RI effects comprised relieving calcium overload, correction of energy metabolism, improvement of endothelial function and inhibiting cell apoptosis.
蒂莲黄酮是从 Moldavuca 龙蒿中富集得到的主要有效黄酮类单体，已被证明具有心脏保护作用。然而，蒂莲黄酮心脏保护的机制在很大程度上仍然未知。本研究旨在探讨蒂莲黄酮预处理对心肌缺血/再灌注损伤的影响，并分析其可能的作用机制。将48只雄性Sprague Dawley大鼠随机分为假手术组、模型心肌缺血/再灌注损伤组（MI/RI）、盐酸普萘洛尔阳性对照组以及高、中、低剂量蒂莲黄酮组（每组n = 8）。蒂莲黄酮组大鼠在手术前一周分别给予1.5、2.5或5.0 mg/kg/d的蒂莲黄酮灌注。阳性对照组给予25 mg/kg/d的普萘洛尔灌注。假手术组和MI/RI组给予生理盐水。通过结扎左冠状动脉前降支30分钟建立MI/RI模型，随后移除结扎线，在处死前观察小鼠120分钟。使用相应的检测试剂盒分析Na⁺-K⁺-ATP酶、Ca²⁺-ATP酶、一氧化氮（NO）、一氧化氮合酶（NOS）和内皮系统相关因子。采用免疫组织化学法测定Bcl-2和Bax的表达水平。通过定量聚合酶链反应测量Caspase-3活性。结果表明，与模型组相比，蒂莲黄酮预处理显著提高了ATP酶活性（P < 0.01和P < 0.05）。在调节内皮功能方面，与模型组相比，给MI/RI大鼠施用蒂莲黄酮后，血清NO水平和心肌NOS活性显著降低（P < 0.01和P < 0.05）。此外，与模型组相比，蒂莲黄酮药物组的内皮素1和血栓素B2血清水平呈剂量依赖性降低，而降钙素基因相关肽和6-酮前列腺素F1α血清水平升高（P < 0.01和P < 0.05）。值得注意的是，蒂莲黄酮的施用显著抑制了细胞凋亡，表现为Bcl-2表达增加，Bax和Caspase-3 mRNA表达水平降低（P < 0.01和P < 0.05）。这些数据表明，蒂莲黄酮预处理对MI/RI大鼠具有强大的心脏保护作用。抗MI/RI作用包括减轻钙超载、纠正能量代谢、改善内皮功能和抑制细胞凋亡。
