Osthole ameliorates acute myocardial infarction in rats by decreasing the expression of inflammatory-related cytokines, diminishing MMP-2 expression and activating p-ERK
Osthole ameliorates acute myocardial infarction in rats by decreasing the expression of inflammatory-related cytokines, diminishing MMP-2 expression and activating p-ERK
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DOI：
10.3892/ijmm.2015.2402
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发表时间：
2016-01-01
影响因子：
5.4
通讯作者：
Tan, Sheng-Yu
中科院分区：
文献类型：
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作者：
Duan, Juan;Yang, Yu;Tan, Sheng-Yu
蛇床子是蛇床子提取物的有效成分，已被证明具有多种药理特性。在本研究中，我们旨在评估蛇床子素对急性心肌梗死（AMI）大鼠模型的心脏保护作用。AMI大鼠分别给予1、3、10 mg/kg蛇床子素或载药治疗4周。测定心肌梗死大鼠梗死面积，采用市售试剂盒检测心肌梗死大鼠酪蛋白激酶（CK）、肌酸激酶MB同工酶（CK-MB）、乳酸脱氢酶（LDH）和心肌肌钙蛋白T （cTnT）活性。采用市售试剂盒检测AMI大鼠全血核因子- κ B （nf - κ B）、肿瘤坏死因子-a （tnf - α）、白细胞介素-1 β和IL-6水平。RT-qPCR检测toll样受体2/4 （TLR2/4）和核苷酸结合寡聚结构域蛋白1/2 （NOD1/2）水平。western blot检测内皮型一氧化氮合酶（eNOS）和丝裂原活化蛋白激酶（MAPK）级联蛋白表达水平，包括细胞外信号调节激酶（ERK）、c-Jun n-末端激酶（JNK）和p38、环氧化酶-2 （COX-2）和基质金属蛋白酶-2 （MMP-2）。我们的研究结果表明，蛇床子素可以显著降低心肌梗死大鼠的梗死面积，降低心肌梗死大鼠心肌梗死后CK、CK- mb、LDH和cTnT的水平，这些心脏保护作用可能与抑制炎症反应、降低MMP-2活性和激活MAPK级联反应有关。
Osthole, the active constituent of Cnidium monnieri extracts, has been shown to have a diverse range of pharmacological properties. In the present study, we aimed to evaluate the cardioprotective effects of osthole in a rat model of acute myocardial infarction (AMI). The rats with AMI were treated with 1, 3 and 10 mg/kg of osthole or the vehicle for 4 weeks. The infarct size of the rats with AMI was measured, and casein kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin T (cTnT) activities in the rats with AMI were analyzed using commercially available kits. The nuclear factor-kappa B (NF-kappa B), tumor necrosis factor-a (TNF-alpha), interleukin (IL)-1 beta and IL-6 levels in whole blood from rats with AMI were also detected using commercially available kits. The levels of Toll-like receptors 2/4 (TLR2/4) and nucleotide-binding oligomerization domain-containing protein 1/2 (NOD1/2) were also detected by RT-qPCR. Moreover, the protein expression levels of endothelial nitric oxide synthase (eNOS) and mitogen-activated protein kinase (MAPK) cascades, including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38, cyclooxygenase-2 (COX-2), as well as matrix metalloproteinase-2 (MMP-2) were all assayed by western blot analysis. Our results revealed that osthole markedly reduced the infarct size, and the levels of CK, CK-MB, LDH and cTnT in the rats with AMI, and that these cardioprotective effects may be associated with the inhibition of inflammatory reactions, the reduction in MMP-2 activity and the activation of MAPK cascades.