Effect of Coptisine Pretreatment on JNK/p38MAPK Signaling Pathway in Rats with Myocardial Ischemia-reperfusion Injury
Objective:To investigate the effect of coptisine pretreatment on c-Jun amino-terminal kinase(JNK)/mitogen-activated protein kinase(p38MAPK)signaling pathway in myocardial ischemia-reperfusion(MI/RI)rats.Methods:Sixty rats were randomly divided into MI/RI group,sham operation group,low dose of coptisine(coptisine-L,50 mg/kg coptisine)group,medium dose of coptisine(coptisine-M,100 mg/kg coptisine)group,and high dose of coptisine(coptisine-H,200 mg/kg coptisine)group and coptisine-H+activator(50 mg/kg coptisine+25 mg/L JNK/p38MAPK pathway activator-anisomycin)group,10 rats in each group.MI/RI rat model was constructed by coronary artery ligation in all groups except the sham operation group.After modeling,the hemodynamic parameters of left chamber pressure maximum rise(LVdp/dtmax),decline rate(LVdp/dtmin),systolic blood pressure,and end diastolic blood pressure were observed.The contents of creatine kinase isoenzyme(CK-MB)and lactate dehydrogenase(LDH)were evaluated by collecting aorta blood from rats.Myocardial tissue was isolated,and myocardial histopathological changes,apoptosis,TNF-α,interleukin-6(IL-6)levels,and JNK/p38MAPK pathway-related protein expression were detected.Results:Compared with the sham operation group,MI/RI group showed a large number of inflammatory cells infiltration,tissue structure disorder,serious pathological damage,LVdp/dtmax,LVdp/dtmin,systolic blood pressure decreased,however,apoptosis rate,end-diastolic blood pressure,LDH,CK-MB,TNF-α,IL-6 content,P-JNK/JNK,P-P38MAPK/p38MAPK expression increased(P<0.05).Compared with MI/RI group,the pathological damage of coptisine-L group,coptisine-M group and coptisine-H group were improved,and LVdp/dtmax,LVdp/dtmin and systolic blood pressure increased,and apoptosis rate,end diastolic blood pressure,LDH,CK-MB,TNF-α,IL-6 content,P-JNK/JNK,P-P38MAPK/p38MAPK expression decreased(P<0.05).Compared with the coptisine-H group,the pathological damage of coptisine-H+activator group was further aggravated,and LVdp/dtmax,LVdp/dtmin and systolic blood pressure decreased,however,apoptosis rate,end diastolic blood pressure,LDH,CK-MB,TNF-α,IL-6 content,P-JNK/JNK,P-P38MAPK/p38MAPK expression increased(P<0.05).Conclusion:Pretreatment with coptisine could reduce myocardial injury in MI/RI rats by inhibiting JNK/p38MAPK pathway.
myocardial ischemia reperfusionmyocardial injurycoptisinec-Jun amino-terminal kinase/mitogen-activated protein kinase signaling pathwayexperimental study
NETL
NSTL
万方数据
