Objective To investigate the effects of emodin on the energy metabolism of cardiomyocytes in rats with heart failure after myocardial infarction and its regulation mechanism on extra-cellular signal regulated kinase (ERK) signaling pathway. Methods The left anterior descending branch was ligated to construct a rat model of myocardial infarction. Successfully modeled animals were randomly divided into a model group, a low-dose group, a middle-dose group, a high-dose group and a control group according to the random number table method, each with 10 animals; at the same time, another 10 rats were taken as a sham operation group. Animals in the sham operation group were only threaded, but not ligated; rats in the low-dose group, middle-dose group, and high-dose group were treated with 20 mg/kg, 40 mg/kg, 60 mg/kg emodin by gavage every day. The rats in the control group were treated with captopril at 10 mg/kg. After 14 days of continuous administration, the left ventricular ejection fraction (LVEF), left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), and ventricular septal thickness(IVS) of each group of rats were statistically analyzed. TUNEL staining was used to detect the apoptosis rate of rat cardiomyocytes. JC-1 staining was used to detect the mitochondrial membrane potential of rat cardiomyocytes. Western blot was used to detect the expressions of mitochondrial respiratory chain complex Ⅰ(complex Ⅰ) protein and p-ERK in myocardial tissue. Results Compared with the sham operation group, the LVEDD, LVESD, myocardial cell apoptosis rate, and the expression of complex I and p-ERK in myocardial tissue were significantly increased in the model group, low, medium, high dose group and the control group. LVEF, IVS and the mitochondrial membrane potential of cardiomyocytes were significantly reduced, and the differences were statistically significant (all P<0.05). Compared with the modern group, the LVEDD, LVESD, myocardial cell apoptosis rate, and the expression of complex I and p-ERK in myocardial tissue were significantly reduced in the low, medium, high dose group and the control group. LVEF, IVS and the mitochondrial membrane potential of cardiomyocytes were increased significantly, and the differences were statistically significant (all P<0.05). Conclusions Emodin can significantly improve the mitochondrial damage and energy metabolism in heart failure rats after myocardial infarction, reduce the apoptosis rate of myocardial tissue, and improve the cardiac function of experimental animals.
Key words
Emodin /
Myocardial infarction /
Heart failure /
Energy metabolism /
Extra-cellular signal regulated kinase signaling pathway
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References
[1] Jenča D, Melenovský V, Stehlik J, et al. Heart failure after myocardial infarction: incidence and predictors[J]. ESC Heart Fail, 2021, 8(1): 222-237. DOI: 10.1002/ehf2.13144.
[2] Molitor M, Rudi WS, Garlapati V, et al. Nox2+ myeloid cells drive vascular inflammation and endothelial dysfunction in heart failure after myocardial infarction via angiotensin II receptor type 1[J]. Cardiovasc Res, 2021, 117(1): 162-177. DOI: 10.1093/cvr/cvaa042.
[3] Sivasangari S, Asaikumar L, Vennila L. Arbutin prevents alterations in mitochondrial and lysosomal enzymes in isoproterenol-induced myocardial infarction: an in vivo study[J]. Hum Exp Toxicol, 2021, 40(1): 100-112. DOI: 10.1177/0960327120945790.
[4] 曹军, 刘志强, 杨东伟. 大黄素对缺氧复氧心肌细胞凋亡、氧化应激及AMPK信号通路蛋白表达的影响[J]. 郑州大学学报(医学版), 2020, 55(1): 74-77. DOI: 10.13705/j.issn.1671-6825.2019.07.132.
[5] 崔勤涛, 王俊华, 刘晓晨, 等. 大黄素激活Nrf2/ARE/HO-1信号通路对心肌缺血再灌注损伤大鼠心功能保护作用[J]. 安徽医科大学学报, 2020, 55(6): 80-86. DOI: 10.19405/j.cnki.issn1000-1492.2020.06.014
[6] Yang Y, Ding Z, Zhong R, et al. Cardioprotective effects of a Fructus Aurantii polysaccharide in isoproterenol-induced myocardial ischemic rats[J]. Int J Biol Macromol, 2020, 55(1): 995-1002. DOI: 10.1016/j.ijbiomac.2019.11.063.
[7] 李昌, 王爱玲, 肖跃红, 等. 汉防己乙素抑制P38 MAPK和ERK1/2的磷酸化缓解心肌缺血再灌注大鼠心肌细胞凋亡和线粒体氧化损伤[J]. 中国药理学与毒理学杂志, 2020, 34(5): 336-342. DOI: 10.3867/j.issn.1000-3002.2020.05.002
[8] Liu Z, Tao B, Fan S, et al. Over-expression of microRNA-145 drives alterations in β-adrenergic signaling and attenuates cardiac remodeling in heart failure post myocardial infarction[J]. Aging (Albany NY), 2020, 12(12): 11603-11622. DOI: 10.18632/aging.103320.
[9] Song Y, Wang B, Zhu X, et al. Human umbilical cord blood-derived MSCs exosome attenuate myocardial injury by inhibiting ferroptosis in acute myocardial infarction mice[J]. Cell Biol Toxicol, 2021, 37(1): 51-64. DOI: 10.1007/s10565-020-09530-8.
[10]Shan B, Li JY, Liu YJ, et al. LncRNA H19 inhibits the progression of sepsis-induced myocardial injury via regulation of the miR-93-5p/SORBS2 axis[J]. Inflammation, 2021, 44(1): 344-357. DOI: 10.1007/s10753-020-01340-8.
[11]K, Miller CA. Substrate for the myocardial inflammation-heart failure hypothesis identified using novel USPIO methodology[J]. JACC Cardiovasc Imaging, 2021,14(2): 365-376. DOI: 10.1016/j.jcmg. 2020. 02.001.
[12]Ye B, Chen X, Dai S, et al. Emodin alleviates myocardial ischemia/reperfusion injury by inhibiting gasdermin D-mediated pyroptosis in cardiomyocytes[J]. Drug Des Devel Ther, 2019, 13(3): 975-990. DOI: 10.2147/DDDT.S195412.
[13]Zhang Y, Song Z, Huang S, et al. Aloe emodin relieves Ang II-induced endothelial junction dysfunction via promoting ubiquitination mediated NLRP3 inflammasome inactivation[J]. J Leukoc Biol, 2020, 108(6): 1735-1746. DOI: 10.1002/JLB.3MA0520-582R.
[14]Su ZL, Hang PZ, Hu J, et al. Aloe-emodin exerts cholesterol-lowering effects by inhibiting proprotein convertase subtilisin/kexin type 9 in hyperlipidemic rats[J]. Acta Pharmacol Sin, 2020, 41(8): 1085-1092. DOI: 10.1038/s41401-020-0392-8.
[15]Ren GD, Y Cui Y, Li WL, et al. Research on cardioprotective effect of irbesartan in rats with myocardial ischemia-reperfusion injury through MAPK-ERK signaling pathway[J]. Eur Rev Med Pharmacol Sci, 2019, 23(12): 5487-5494. DOI: 10.26355/eurrev_201906_18218.
[16]Zhang J, Wang L, Xie W, et al. Melatonin attenuates ER stress and mitochondrial damage in septic cardiomyopathy: a new mechanism involving BAP31 upregulation and MAPK-ERK pathway[J]. J Cell Physiol, 2020, 235(3): 2847-2856. DOI: 10.1002/jcp.29190.
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