| Objective Heart failure(HF)is the final stage of the development of various heart diseases.HF has many causes.Cardiomyocyte apoptosis is an essential element in the development of HF.This study was to investigate the effect of JNK phosphorylation on the proapoptotic protein Bax and the anti-apoptotic protein Bcl-2 in cardiomyocytes of HF rats,which may affect the apoptosis of cardiomyocytes;to explore the hexarelin Whether it is possible to reduce the number of cardiomyocyte apoptosis and improve HF by inhibiting this regulation of JNK.Methods Clean grade,80 SD rats,weight(220±20g).Divided into four groups: normal group,sham operation group,HF group,and HF+hexarelin group.We used the left anterior descending coronary artery ligation to produce a model of HF after myocardial infarction.During the operation,ECG monitoring was performed.Serum or hexarelin(25 ?g/kg once a day)was given 4 weeks after surgery for 4 weeks.After 8 weeks of operation,echocardiography was used to detect cardiac function in each group.HE staining was used to observe the morphology of cardiomyocytes.Immunohistochemistry was used to measure pJNK,Bcl-2,Bax,and Caspase-3 in rat myocardial tissue.The positive expression level of protein was detected by Western Blot.The expression levels of JNK,p-JNK,Bcl-2,Bax,Caspase-3 and Cleaved Caspase-3 protein in myocardial tissue of each group were determined.Results1.ECG resultsBefore the operation,the waveforms of the electrocardiogram of the rats were normal.At the end of the operation,transient arrhythmias occurred in some rats in the sham operation group.In the model group,the T wave was high and the ST segment was upright.2.Echocardiographic resultsAt the end of the 8th week,echocardiography was performed and the left ventricle was dilated.Compared with the normal group,the left ventricular systolic diameter and left ventricular diastolic diameter of the HF group were significantly increased(p<0.05).Blood scores were significantly reduced(p < 0.05).Compared with the HF group,the left ventricular systolic diameter and the left ventricular systolic diameter in the HF+hexarelin group were significantly smaller than those in the model group(p<0.05),and the left ventricular ejection fraction was significantly increased(p<0.05).3.HE staining resultsThe cardiomyocytes of the normal group and the sham operation group were arranged neatly,the trend was consistent,and the transverse lines of the myocardial fibers were clearly visible.And the dyeing is uniform,and the shape of the core of the cardiomyocytes is regular.In the HF group,the damaged cardiomyocytes showed a large amount of necrosis,the myocardial cells were disordered,and the myocardial transverse stripes disappeared.The myocardial cells in the HF+hexarelin group were arranged regularly,and some of the myocardial fibers were still visible in the transverse stripes.4.Immunohistochemistry resultsThe positive expression level of p-JNK protein was significantly higher in the model group than in the sham operation group(p<0.05),and was significantly lower in the treatment group than in the model group(p<0.05).The positive expression level of Bax protein was significantly higher in the model group than in the sham operation group(p<0.05),and the treatment group was significantly lower than the model group(p<0.05).The positive expression level of Bcl-2 protein was significantly lower in the model group than in the sham operation group(p<0.05),and the treatment group was significantly higher than the model group(p<0.05).The positive expression level of Caspase-3 protein was significantly higher in the model group than in the sham operation group(p<0.05),and was significantly lower in the treatment group than in the model group(p<0.05).5.Western Blot test resultsThe ratio of p-JNK/JNK was significantly higher in the model group than in the sham group(p<0.05),and was significantly lower in the treatment group than in the model group(p<0.05).The expression of Bax protein was significantly higher in the model group than in the sham operation group(p<0.05),and was significantly lower in the treatment group than in the model group(p<0.05).The expression of Bcl-2 protein was significantly lower in the model group than in the sham operation group(p<0.05),and was significantly higher in the treatment group than in the model group(p<0.05).The ratio of Cleaved Caspase-3/Caspase-3 was significantly higher in the model group than in the sham group(p<0.05),and was significantly lower in the treatment group than in the model group(p<0.05).conclusionThe results showed that hexarelin can significantly inhibit the apoptosis of cardiomyocytes in the HF model after myocardial infarction.The mechanism may be through inhibition of JNK activation,thereby inhibiting the expression of proapoptotic protein Bax and increasing antiapoptotic protein Bcl-2.Expression ultimately inhibits the activation of the effector Caspase-3.Thereby protecting the cardiomyocytes and improving HF. |
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