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?-?,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-?,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-?[?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-?,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.