Regulation of serum lipidomics and amino acid profiles of rats with acute myocardial ischemia by Salvia miltiorrhiza and Panax notoginseng herb pair.,Phytomedicine

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Regulation of serum lipidomics and amino acid profiles of rats with acute myocardial ischemia by Salvia miltiorrhiza and Panax notoginseng herb pair.
Phytomedicine ( IF 6.7 ) Pub Date : 2019-12-26 , DOI: 10.1016/j.phymed.2019.153162
Huijuan Tao ₁ , Xinyu Yang ₂ , Wenxiao Wang ₃ , Shijun Yue ₃ , Zongjin Pu ₄ , Yuxi Huang ₃ , Xuqin Shi ₄ , Jiaqian Chen ₄ , Guisheng Zhou ₄ , Yanyan Chen ₃ , Ming Zhao ₄ , Yuping Tang ₁ , Jin-Ao Duan ₄

Affiliation

Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an 712046, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Beijing Key Laboratory of Bio-Characteristic Profiling for Evaluation of Rational Drug Use, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.
Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an 712046, China.
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.

BACKGROUND Salvia miltiorrhiza and Panax notoginseng herb pair (DQ) has been widely used in traditional Chinese medicine for a long history to prevent and treat the coronary heart disease. However, its protective mechanisms against myocardial ischemia during coronary heart disease remain not well-understood. PURPOSE In this study, we aimed to explore the protective mechanisms of DQ on myocardial ischemia from the perspective of serum lipidomics and amino acids (AAs). METHODS Rats were orally administrated with low-dose DQ (L-DQ, 0.24 g/kg) and high-dose DQ (H-DQ, 0.96 g/kg) for two weeks and subcutaneously injected with isoproterenol (ISO, 65 mg/kg) for two consecutive days (13th and 14th days) to induce acute myocardial ischemia (AMI). Heart histopathology and serum biochemical indices were examined. The specifically altered serum lipid metabolites were profiled via lipidomics approach, while serum AA profiles were analyzed using UHPLC-TQ-MS/MS. RESULTS Cardiac marker enzymes (CK, CK-MB, LDH and cTn-I) were significantly upregulated in AMI rats with some of which significantly dropped to normal level in L- and H-DQ groups. Serum TC, TG, HDL, LDL, VLDL and FFA were improved in AMI rats treatment with L- and H-DQ. Further, the PCA based on lipidomics showed serum lipid metabolites in L- and H-DQ groups were closer to control group than that in model group. Compared with model group, H-DQ pretreatment significantly reduced SM (d34:1) and CE (20:4), and increased FA (20:5), PC (26:1), TG (56:9), TG (54:7), MG (17:0), Cer (d32:0) and Cer (d34:0), whereas L-DQ significantly alleviated the perturbed levels of CE (20:4), FA (20:5), MG (17:0), and SM (d34:1). Moreover, there was a significant increment for leucine, isoleucine, valine, phenylalanine, lysine and glutamate but a significant reduction for tryptophan in the serum of rats in model group as compared to control group. Intriguingly, H-DQ could significantly decrease the levels of glutamate, lysine, isoleucine, and BCAAs (the sum of leucine, isoleucine and valine) after AMI, while L-DQ had no significant effects on the above altered AAs. The Western blotting results implied that H-DQ could promote the myocardial BCAA catabolism in AMI rats by activation of BCKDHA, whereas by inhibition of BCKDHK. CONCLUSION This study presents evidence for the therapeutic effects of DQ on AMI injury, in part, via co-regulating lipid and AA metabolisms.

中文翻译：

丹参和三七合剂对急性心肌缺血大鼠血清脂质组学和氨基酸谱的调节。

背景技术丹参和三七药草对（DQ）在预防和治疗冠心病方面已有很长的历史。然而，其在冠心病期间对心肌缺血的保护机制仍未被很好地理解。目的在本研究中，我们旨在从血清脂质组学和氨基酸（AAs）的角度探讨DQ对心肌缺血的保护机制。方法大鼠口服低剂量DQ（L-DQ，0.24 g / kg）和高剂量DQ（H-DQ，0.96 g / kg）持续两周，并皮下注射异丙肾上腺素（ISO，65 mg / kg ）连续两天（第13天和第14天）诱发急性心肌缺血（AMI）。检查心脏组织病理学和血清生化指标。通过脂质组学方法对特异改变的血清脂质代谢产物进行了分析，同时使用UHPLC-TQ-MS / MS分析了血清AA的分布。结果在AMI大鼠中，心脏标志物酶（CK，CK-MB，LDH和cTn-1）显着上调，其中一些在L-和H-DQ组中显着下降至正常水平。用L-和H-DQ治疗的AMI大鼠的血清TC，TG，HDL，LDL，VLDL和FFA得到改善。此外，基于脂质组学的PCA显示，L-和H-DQ组的血清脂质代谢产物比模型组更接近于对照组。与模型组相比，H-DQ预处理显着降低了SM（d34：1）和CE（20：4），并增加了FA（20：5），PC（26：1），TG（56：9），TG（ 54：7），MG（17：0），Cer（d32：0）和Cer（d34：0），而L-DQ显着减轻了CE（20：4），FA（20：5）， MG（17：0），和SM（d34：1）。此外，与对照组相比，模型组大鼠血清中的亮氨酸，异亮氨酸，缬氨酸，苯丙氨酸，赖氨酸和谷氨酸显着增加，而色氨酸显着减少。有趣的是，H-DQ可以显着降低AMI后的谷氨酸，赖氨酸，异亮氨酸和BCAAs（亮氨酸，异亮氨酸和缬氨酸之和）的水平，而L-DQ对上述改变后的AAs无明显影响。蛋白质印迹结果表明，H-DQ可以通过激活BCKDHA而抑制BCKDHK来促进AMI大鼠心肌BCAA分解代谢。结论本研究提供了DQ对AMI损伤的治疗作用的证据，部分地是通过共同调节脂质和AA代谢。与对照组相比，模型组大鼠血清中的苯丙氨酸，赖氨酸和谷氨酸含量显着降低，但色氨酸显着降低。有趣的是，H-DQ可以显着降低AMI后的谷氨酸，赖氨酸，异亮氨酸和BCAAs（亮氨酸，异亮氨酸和缬氨酸之和）的水平，而L-DQ对上述改变后的AAs无明显影响。蛋白质印迹结果表明，H-DQ可以通过激活BCKDHA而抑制BCKDHK来促进AMI大鼠心肌BCAA分解代谢。结论本研究提供了DQ对AMI损伤的治疗作用的证据，部分地是通过共同调节脂质和AA代谢。与对照组相比，模型组大鼠血清中的苯丙氨酸，赖氨酸和谷氨酸含量显着降低，但色氨酸显着降低。有趣的是，H-DQ可以显着降低AMI后的谷氨酸，赖氨酸，异亮氨酸和BCAAs（亮氨酸，异亮氨酸和缬氨酸之和）的水平，而L-DQ对上述改变后的AAs无明显影响。蛋白质印迹结果表明，H-DQ可以通过激活BCKDHA而抑制BCKDHK来促进AMI大鼠心肌BCAA分解代谢。结论本研究提供了DQ对AMI损伤的治疗作用的证据，部分地是通过共同调节脂质和AA代谢。H-DQ可以显着降低AMI后的谷氨酸，赖氨酸，异亮氨酸和BCAAs（亮氨酸，异亮氨酸和缬氨酸之和）的水平，而L-DQ对上述改变后的AA无明显影响。蛋白质印迹结果表明，H-DQ可以通过激活BCKDHA而抑制BCKDHK来促进AMI大鼠心肌BCAA分解代谢。结论本研究提供了DQ对AMI损伤的治疗作用的证据，部分地是通过共同调节脂质和AA代谢。H-DQ可以显着降低AMI后的谷氨酸，赖氨酸，异亮氨酸和BCAAs（亮氨酸，异亮氨酸和缬氨酸之和）的水平，而L-DQ对上述改变后的AA无明显影响。蛋白质印迹结果表明，H-DQ可以通过激活BCKDHA而抑制BCKDHK来促进AMI大鼠心肌BCAA分解代谢。结论本研究提供了DQ对AMI损伤的治疗作用的证据，部分地是通过共同调节脂质和AA代谢。

更新日期：2019-12-27

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