Study Of Shexiang Tongxin Dropping Pill In Improving Coronary Microcirculation Disturbance And Cardiac Function After Ischemia-reperfusion In Pigs

BACKGROUND:The development of percutaneous coronary intervention technology(PCI)enables patients with coronary heart disease to recover blood-supply in a short period of time,reduce cardiac ischemic injury,improve patient survival and quality of life,but the incidence of coronary slow circulation / no reflow caused by coronary microcirculation disturbance after reperfusion injury is as high as 10%-30%,this part of the patient's cardiac function does not improve,immediate and long-term significantly increased the incidence of cardiovascular events and mortality.Its pathogenesis involves a variety of factors and is not fully understood.Therefore,effective prevention and treatment of coronary microcirculation disorder after ischemia-reperfusion surgery is still a difficult problem facing the world.Shexiang Tongxin Dropping Pill(STDP)has a significant effect on coronary heart disease,heart failure,slow blood flow after PCI,and other diseases,and has the effects of inhibiting oxidation,inflammatory response,stabilizing plaques and protecting endothelial function etc.It has a good application prospect for the prevention and treatment of cardiovascular diseases.Previous studies have found that STDP can improve the degree of microcirculatory disturbance after myocardial infarction,but its mechanism of action remains to be determined.OBJECTIVETo investigate the mechanism of Shexiang Tongxin Drop Pills(STDP)on the coronary circulation microcirculation disturbance(CMD)induced by ischemia-reperfusion in pigs.METHODSMale Wuzhishan mini-pigs were randomly divided into a sham operation group,a model group and a STDP treatment group,with 6 in each group.A balloon-blocked proximal left anterior descending branch and reperfused was performed to establish a CMD model in all groups except the sham operation group.At 0th and 8th week,blood sampel was taken to test blood biochemical index,coronary angiography and echocardiography were performed,statistics of vessel lumen diameter and TIMI frame count(CTFC)were computed.The myocardium of the proximal coronary artery distribution was collected for hematoxylin-eosn(HE)staining after the animals were sacrificed at 8th week.WB was used to detect the expression of silencing information regulator(Sirt1),peroxidase proliferator-activated receptor-? coactivator-1?(PGC-1?),peroxisome proliferator-activated receptor ?(PPAR?),extracellular signal-regulated kinase1/2(ERKI/2),Toll-like receptor 4(TLR4),uncoupling protein 2(UCP2)in myocardial tissue.RESULTSBefore and after taking the drugs,the body mass,blood lipids(total cholesterol,triglycerides,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol),liver and kidney function indicators,creatine kinase isoenzyme,troponin-I,the diameter of the anterior descending vessel in the three groups of experimental animals was not significantly different(P> 0.05).At 8th week of the experiment,compared with the sham operation group,lactate dehydrogenase(LDH)and creatine kinase(CK)in other groups were significantly increased;compared with the model group,the STDP-treated group LDH and CK were significantly reduced(P < 0.05).At 0th week of the the experiment,the number of CTFC frames in each groupwas not significantly different(P>0.05);compared with the model group,the number of CTFC frames in the STDP-treated group was lower(P<0.05).At week 0th of the experiment,there were no statistically significant differences in the indexes of cardiac color Doppler ultrasound in the three groups of experimental animals(P> 0.05).At 8th week of the experiment,compared with the sham operation group,the interventricular septal thickness at end-diastole,left ventricular end-diastole dimension,end-diastole volume,interventricular septal thickness at end-systole and left ventricular mass increased(P <0.05);compared with the model group,the above indicators of the STDP-treated group decreased(P <0.05).The HE staining results showed that compared with the sham operation group,myocardial microvascular congestion,thrombosis and peripheral inflammation infiltration,myocardial fiber atrophy,and myocardial interstitial inflammatory cell infiltration were observed in the model group.Compared with the model group,the STDP-treated group had no obvious hyperemia,the inflammation and infiltration around blood vessels were reduced,and the myocardial muscle fiber atrophy was exacerbated,but myocardial interstitial inflammation infiltration was less severe.Compared with the sham operation group,the expressions of Sirt1,PGC-1?,and PPAR? were down-regulated and the expressions of ERK1/ 2,TLR4,and UCP2 were up-regulated in the myocardial tissues of the remaining groups.Compared with the model group,the expression levels of Sirt1,PGC-1?,and PPAR? were higher,and t ERK1 / 2,TLR4,and UCP2 were lower in the drug-treated group.CONCLUSIONSTDP may exert anti-inflammatory and regulate energy metabolism effects through Sirt1,PGC-1?,PPAR?,ERK1/ 2,TLR4,UCP2 to improve coronary microcirculation disturbance and cardiac dysfunction after ischemia-reperfusion.