|
|
|
|
|
| Protective effects of different doses of 6-Gingerol on myocardial ischemia-reperfusion injury in rats |
| Zhao Wei-kun, Xu Tong-tong, Lu Xiang-wei, Wu Qi, Qin Qiu-yu |
| The Department of Integrated TCM and Western Medicine Health Care Ward, Affiliated Hospital of Guilin Medical University, Guilin 541001, China |
|
|
|
|
Abstract Objective To investigate the protective effects of different doses of 6-Gingerol on myocardial ischemia-reperfusion injury (MIRI) in rats. Methods The rat MIRI model was prepared by ligation of left anterior descending coronary artery (LAD) in rats for 0.5 h. Forty Sprague-Dawley (SD) rats were randomly divided into 5 groups: sham operation group (Sham group), MIRI control group (I/R group), 6-G low, medium and high dose groups, and each group consists of 8 mice. In the Sham group, only the thorax was opened and LAD ligation was not performed. The MIRI model was prepared in I/R group and administered via the tail vein (3, 6, 12 mg/kg) 0.5 h before surgery in 6-G+MIRI group. Then we detected the levels of serum interleukin (IL)-6, serum tumor necrosis factor (TNF)-α, serum creatine phosphate kinase (CK), serum creatine phosphate kinase isoenzyme (CK-MB) and serum troponin T (cTnT) by enzyme-linked immunosorbent assay (ELISA) in each group. The indexes of the left ventricular ejection fraction (LVEF), the left ventricular fractional shortening (LVFS), the left ventricular systolic pressure (LVSP), the left ventricular end-diastolic pressure (LVEDP), the maximum up/down rate of the left ventricular pressure (±dp/dtmax) were collected by using a biological function system (BL-420S). Hematoxylin-eosin (HE) staining was used to observe the pathological changes of the myocardium under light microscope. Results Compared with the Sham group, the levels of IL-6, TNF-α, myocardial enzymes (CK, CK-MB) and cTnT were increased in other groups (P<0.05). The cardiac function (LVEF, LVFS, LVSP,+dp/dtmax, -dp/dtmax) was decreased (P<0.05), while LVEDP increased (P<0.05). Compared with I/R group, the middle-dose group significantly decreased the levels of IL-6［(34.80±5.10) pg/mL vs. (46.95±5.10) pg/mL］and TNF-α (30.39±3.93) pg/mL vs. (40.46±3.39) pg/mL］(P<0.05), decreased serum the levels of CK［(1.35±0.02) mU/mL vs. (1.48±0.03) mU/mL］, CK-MB［(1.98±0.41) ng/mL vs. (2.59±0.60) ng/mL］, cTnT［(117.00±13.67) pg/mL vs. (148.55±14.76) pg/mL］(P<0.05), increased cardiac function LVEF (41.38±3.74)% vs. (30.00±4.69)%］, LVFS［(34.63±4.44)% vs. (21.25±4.43)%, LVSP［(137.13±5.41) mm Hg vs. (124.75±4.17) mm Hg］,+dp/dtmax［(4323.25±398.17) mm Hg/s vs. (3530.36±245.02) mm Hg/s］, and -dp/dtmax［(3188.38±248.06) mm Hg/s vs.［(2395.25±315.60) mm Hg/s］(P<0.05), while LVEDP［(2.31±0.58) mm Hg vs. (3.65±0.44) mm Hg］decreased (P<0.05). Myocardial tissue damage was reduced. There was no significant difference in the levels of IL-6, TNF-α, myocardial enzymes, cTnT, cardiac function in the low and high dose groups (P>0.05) and myocardial tissue damage was not significantly alleviated. Conclusion The middle-dose group can reduce MIRI. The mechanism may be through inhibiting inflammatory reaction, protecting cardiomyocytes and improving cardiac function in rats.
|
|
|
|
Corresponding Authors:
Xu Tong-tong, E-mail: 2655820200@qq.com
|
|
|
|
| ［1］Yu P, Zhang J, Yu S, et al. Protective Effect of Sevoflurane Postconditioning against Cardiac Ischemia/Reperfusion Injury via Ameliorating Mitochondrial Impairment, Oxidative Stress and Rescuing Autophagic Clearance［J］. PLoS One, 2015, 10(8):e01 34 666.
［2］Li J, Xiang X, Gong X, et al. Cilostazol protects mice against myocardium ischemic/reperfusion injury by activating a PPARγ/JAK2/STAT3 pathway［J］. Biomed Pharmacother, 2017, 94:995-1001.
［3］Binder A, Ali A, Chawla R, et al. Myocardial protection from ischemia-reperfusion injury post coronary revascularization［J］. Expert Rev Cardiovasc Ther, 2015, 13(9):1045-1057.
［4］Wang Z, Wang Y, Ye J, et al. bFGF attenuates endoplasmic reticulum stress and mitochondrial injury on myocardial ischaemia/reperfusion via activation of PI3K/Akt/ERK1/2 pathway［J］. J Cell Mol Med, 2015, 19(3):595-607.
［5］Liebert A, Krause A, Goonetilleke N, et al. A Role for Photobiomodulation in the Prevention of Myocardial Ischemic Reperfusion Injury: A Systematic Review and Potential Molecular Mechanisms［J］. Sci Rep, 2017, 7:42 386.
［6］Montecucco F, Liberale L, Bonaventura A, et al. The Role of Inflammation in Cardiovascular Outcome［J］. Curr Atheroscler Rep, 2017, 19(3):11.
［7］Wang S, Zhang C, Yang G, et al. Biological properties of 6-gingerol: a brief review［J］. Nat Prod Commun, 2014, 9(7):1027-1030.
［8］吕祥威,徐彤彤.6-姜酚抑制氧化应激减轻大鼠心肌缺血/再灌注损伤［J］.临床心血管病杂志，2017，33（6）：575-579.
［9］Xu Z, Mcelhanon KE, Beck EX, et al. A Murine Model of Myocardial Ischemia-Reperfusion Injury［J］. Method Mol Biol, 2018, 1717:145-153.
［10］Gragnano F, Sperlongano S, Golia E, et al. The Role of von Willebrand Factor in Vascular Inflammation: From Pathogenesis to Targeted Therapy［J］. Mediators Inflamm, 2017, 2017:5 620 314.
［11］Ma Y, Iyer RP, Jung M, et al. Cardiac Fibroblast Activation Post-Myocardial Infarction: Current Knowledge Gaps［J］. Trends Pharmacol Sci, 2017, 38(5):448-458.
［12］Li J, Zhang H, Zhang C. Role of inflammation in the regulation of coronary blood flow in ischemia and reperfusion: Mechanisms and therapeutic implications［J］. J Mol Cell Cardiol, 2012, 52(4): 865-872.
［13］Jing L, Wang JG, Zhang JZ, et al. Upregulation of ICAM-1 in diabetic rats after transient forebrain ischemia and reperfusion injury［J］. J Inflamm (Lond), 2014, 11(1):35.
［14］Heusch G, Gersh BJ. The pathophysiology of acute myocardial infarction and strategies of protection beyond reperfusion: a continual challenge［J］. Eur Heart J, 2017, 38(11):774-784.
［15］Yuan X, Xiang Y, Zhu N, et al. Salvianolic acid A protects against myocardial ischemia/reperfusion injury by reducing platelet activation and inflammation［J］. Exp Ther Med, 2017, 14(2):961-966.
［16］Gao C, Liu Y, Yu Q, et al. TNF-α antagonism ameliorates myocardial ischemia-reperfusion injury in mice by upregulating adiponectin［J］. Am J Physiol Heart Circ Physiol, 2015, 308(12):H1583-1591.
［17］Jong WM, Ten Cate H, Linnenbank AC, et al. Reduced acute myocardial ischemia-reperfusion injury in IL-6-deficient mice employing a closed-chest model［J］. Inflamm Res, 2016, 65(6):489-499.
［18］Li Y, Xu B, Xu M, et al. 6-Gingerol protects intestinal barrier from ischemia/reperfusion-induced damage via inhibition of p38 MAPK to NF-κB signalling［J］. Pharmacol Res, 2017, 119:137-148.
［19］Huang M, Yang D, Xiang M, et al. Role of interleukin-6 in regulation of immune responses to remodeling after myocardial infarction［J］. Heart Fail Rev, 2015, 20(1):25-38.
［20］Semwal RB, Semwal DK, Combrinck S, et al. Gingerols and shogaols: Important nutraceutical principles from ginger［J］. Phytochemistry, 2015, 117:554-568.
［21］Mohd Yusof YA. Gingerol and Its Role in Chronic Diseases［J］. Adv Exp Med Biol, 2016, 929:177-207.
［22］Li XH, Mcgrath KC, Tran VH, et al. Attenuation of Proinflammatory Responses by S-［6］-Gingerol via Inhibition of ROS/NF-Kappa B/COX2 Activation in HuH7 Cells［J］. Evid Based Complement Alternat Med, 2013, 2013:146 142.
［23］Justo OR, Simioni PU, Gabriel DL, et al. Evaluation of in vitro anti-inflammatory effects of crude ginger and rosemary extracts obtained through supercritical CO2 extraction on macrophage and tumor cell line: the influence of vehicle type［J］. BMC Complement Altern Med, 2015, 15:390.
［24］Wang W, Li CY, Wen XD, et al. Plasma pharmacokinetics, tissue distribution and excretion study of 6-gingerol in rat by liquid chromatograph-electrospray ionization time-of-flight mass Spectrometry［J］. J Pharm Biomed Anal, 2009, 49(4):1070-1074.
［25］Qiu JX, Zhou ZW, He ZX, et al. Estimation of the binding modes with important human cytochrome P450 enzymes, drug interaction potential, pharmacokinetics, and hepatotoxicity of ginger components using molecular docking, computational, and pharmacokinetic modeling studies［J］. Drug Des Devel Ther, 2015, 9:841-866.
［26］Ohizumi Y, Sasaki S, Shibusawa K, et al. Clastogenic effect of ginger rhizome in mice Stimulation of sarcoplasmic reticulum Ca(2+)-ATPase by gingerol analogues［J］. Biol Pharm Bull, 1996, 19(10):1377-1379.
［27］Lv X, Xu T, Wu Q, et al. 6-Gingerol Activates PI3K/Akt and Inhibits Apoptosis to Attenuate MyocardialIschemia/Reperfusion Injury［J］. Evid Based Complement Alternat Med, 2018, 2018:9024034. |
|
|
|
Address: 1 North 2nd Street,
Zhongguancun, 
