Effects Of Different Doses Of 6-Gingerol On Inflammatory Response With Myocardial Ischemia Reperfusion Injury

Objective:To investigate whether the effect of 6-Gingerol on myocardial ischemia reperfusion injury（MIRI）inflammatory response in rats is related to its dose.Methods:The rat MIRI model was prepared by ligation of the left anterior descending coronary artery（LAD）of rats for 0.5 h and then reperfusion.Forty Sprague-Dawley（SD）rats were randomly divided into 5 groups:Sham operation group（Sham group）,MIRI group（I/R group）,6-Gingerol low,medium and high dose groups,8 rats in each group.The Sham group only had thoracotomy and no LAD ligation;each group of 6-Gingerol was given different doses of 6-gingerol（3,6,12 mg/kg）via tail vein,and a rat MIRI model was made0.5 h later.I/R group and 6-gingerol group were subjected to ischemia for 0.5 h and reperfusion for 2 h.After that,specimens were collected and heart function was detected.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/dt_max)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/dt_max,-dp/dt_max)was decreased（P<0.05）,while LVEDP increased（P<0.05）.Compared with the 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）mmHg vs.（124.75±4.17）mmHg],+dp/dt_max[（4323.25±398.17）mmHg/s vs.（3530.36±245.02）mmHg/s],and-dpdt_max[（3188.38±248.06）mmHg/s vs.（2395.25±315.60）mmHg/s]（P<0.05）,while LVEDP[（2.31±0.58）mmHg vs.（3.65±0.44）mmHg]decreased（P<0.05）.Myocardial tissue damage is alleviated,mainly manifested as oozing necrosis and inflammatory cell infiltration.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）.There was no significant reduction in myocardial tissue damage,and there was still a large amount of red blood cell exudation and inflammatory cell infiltration.Conclusions:Only medium doses of 6-Gingerol（6mg/kg）can reduce MIRI,and its mechanism may protect cardiomyocytes and improve cardiac function in rats by inhibiting inflammatory responses.