Cardioprotective effect of paeonol and danshensu combination on isoproterenol-induced myocardial injury in rats.
Cardioprotective effect of paeonol and danshensu combination on isoproterenol-induced myocardial injury in rats.
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DOI：
10.1371/journal.pone.0048872
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Qiu PC
中科院分区：
文献类型：
--
作者：
Li H;Xie YH;Yang Q;Wang SW;Zhang BL;Wang JB;Cao W;Bi LL;Sun JY;Miao S;Hu J;Zhou XX;Qiu PC
传统中草药厚朴和丹参在临床实践中被认为具有心脏保护作用。然而，联合使用的理由仍不清楚。本研究旨在探讨丹皮酚和丹参素（分别为丹皮和丹参的代表性活性成分）对异丙肾上腺素诱导的大鼠心肌梗死的保护作用及其机制。Sprague道利大鼠单独或联合经口给药21天，给予阿丹酚（80 mg kg−1）和丹参素（160 mg kg−1）。在该阶段结束时，皮下给予大鼠异丙肾上腺素（85 mg kg-1）以诱导心肌损伤。诱导后，用戊巴比妥钠（35 mg kg-1）麻醉大鼠，记录心电图，然后处死，并进行心脏组织的生化分析。用异丙肾上腺素诱导的大鼠ST段、梗死面积、血清标志酶（CK-MB、LDH、AST和ALT）、cTnI、TBARS水平、Bax和Caspase-3蛋白表达显著升高（P<0.001），内源性抗氧化剂（SOD、CAT、GPx、GR和GST）活性和Bcl-2蛋白表达显著降低。丹皮酚和丹参素联合治疗组ST段抬高、心肌梗死面积、cTnI、TBARS、Bax和Caspase-3蛋白表达较单药治疗组显著降低（P<0.001），内源性抗氧化剂活性和Bcl-2、Nrf 2蛋白表达显著升高（P<0.001）。本研究旨在探讨丹皮酚与丹参素合用对异丙肾上腺素诱导的大鼠心肌梗死的保护作用。其机制可能与激活Nrf 2信号通路增强抗氧化防御系统，调节Bax、Bcl-2和Caspase-3的表达而抗凋亡有关。为临床中药组合用药的合理性提供实验依据。
Traditional Chinese medicinal herbs Cortex Moutan and Radix Salviae Milthiorrhizaeare are prescribed together for their putative cardioprotective effects in clinical practice. However, the rationale of the combined use remains unclear. The present study was designed to investigate the cardioprotective effects of paeonol and danshensu (representative active ingredient of Cortex Moutan and Radix Salviae Milthiorrhizae, respectively) on isoproterenol-induced myocardial infarction in rats and its underlying mechanisms. Paeonol (80 mg kg−1) and danshensu (160 mg kg−1) were administered orally to Sprague Dawley rats in individual or in combination for 21 days. At the end of this period, rats were administered isoproterenol (85 mg kg−1) subcutaneously to induce myocardial injury. After induction, rats were anaesthetized with pentobarbital sodium (35 mg kg−1) to record electrocardiogram, then sacrificed and biochemical assays of the heart tissues were performed. Induction of rats with isoproterenol resulted in a marked (P<0.001) elevation in ST-segment, infarct size, level of serum marker enzymes (CK-MB, LDH, AST and ALT), cTnI, TBARS, protein expression of Bax and Caspase-3 and a significant decrease in the activities of endogenous antioxidants (SOD, CAT, GPx, GR, and GST) and protein expression of Bcl-2. Pretreatment with paeonol and danshensu combination showed a significant (P<0.001) decrease in ST-segment elevation, infarct size, cTnI, TBARS, protein expression of Bax and Caspase-3 and a significant increase in the activities of endogenous antioxidants and protein expression of Bcl-2 and Nrf2 when compared with individual treated groups. This study demonstrates the cardioprotective effect of paeonol and danshensu combination on isoproterenol-induced myocardial infarction in rats. The mechanism might be associated with the enhancement of antioxidant defense system through activating of Nrf2 signaling and anti-apoptosis through regulating Bax, Bcl-2 and Caspase-3. It could provide experimental evidence to support the rationality of combinatorial use of traditional Chinese medicine in clinical practice.