Effects of Ligusticum Chuanxiong Polysaccharide on Myocardial Ischemia-reperfusion Injury in Rats by Regulating p38 MAPK/NF-κB Signaling Pathway
Objective:To investigate the effect of ligusticum chuanxiong polysaccharide(LCPS)on myocardial ischemia-reperfusion injury(MIRI)in rats by regulating the p38 mitogen activated protein kinase(p38 MAPK)/nuclear factor-KB(NF-KB)signaling pathway.Methods:After numerical coding,144 rats were divided into sham operation group,model group,verapamil hydrochloride(VH)group(20 mg/kg),LCPS low-dose group(50 mg/kg),LCPS medium-dose group(100 mg/kg),and LCPS high-dose group(200 mg/kg)according to random number table method,with 24 rats in each group.After 14 days of pretreatment,the MIRI rat model was established by blocking the left anterior descending coronary artery for 30 min.After 2 h reperfusion,myocardial infarction size and cardiac function indexes[left ventricular end-diastolic pressure(LVEDP),left ventricular end-systolic pressure(LVESP),maximum rise rate of left ventricular pressure(+dp/dtmax),maximum fall rate of left ventricular pressure(-dp/dtmax)[were detected by 2,3,5-triphenyletetrazolium chloride(TTC)staining,cardiac ultrasonography and hematoxylin-eosin(HE)staining respectively and pathological changes of myocardial tissue in rats were observed.The levels of serum myocardial enzymes and inflammatory factors were detected by enzyme-linked immunosorbent assay(ELISA).The expression of p38 MAPK/NF-κB signal pathway related proteins in myocardial tissue were detected by Western Blot.Results:Compared with the sham operation group,myocardial infarction area,LVEDP,pathological score,levels of myocardial enzymes[lactate dehydrogenase(LDH),creatine kinase isoenzyme(CK-MB),cardiac troponin Ⅰ(cTnⅠ)],inflammatory factors[interleukin(IL)-1 β,IL-6,tumor necrosis factor(TNF)-α],p-p38 MAPK,the relative expression of MAPK and p-NF-κB p65 protein and the ratio of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 in the model group increased,while LVESP,+dp/dtmax and-dp/dtmax decreased,with statistical significance(P＜0.05).Compared with the model group,myocardial infarction area,LVEDP,pathological score,levels of myocardial enzymes,inflammatory factor,the relative expression of p-p38 MAPK,p-NF-κB p65 protein and the ratio of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 in the VH group,LCPS medium-dose group and LCPS high-dose group decreased,LVESP,+dp/dtmax,-dp/dtmax increased,and the differences were statistically significant(P＜0.05).The above effects of LCPS were dose-dependent.Except for+dp/dtmax,-dp/dtmax and IL-1β,LCPS high-dose group showed better effects on other indexes than VH group(P＜0.05).Conclusion:LCPS showed protective effects on MIRI and cardiac function in rats,its mechanism might be related to the inhibition of p38 MAPK/NF-κB signaling pathway and it mediated inflammatory response.
myocardial ischemia-reperfusion injuryligusticum chuanxiong polysaccharidecardiac functionp38 mitogen-activated protein kinase/nuclear factor-κB signaling pathwayinflammatory responseratexperimental study
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