| Part one:To explore the in vivo application method of JNK signal pathway inhibitor1.ObjectiveTo explore the method for the long-term in vivo application of JNK signaling pathway inhibitor (SP600125).2.MethodsThe40New Zealand rabbits were randomly divided into8groups:control group, model control group, high dose JNK group, low dose JNK group, JNK group, DMSO model group, DMSO blank group, positive control group. All the experimental groups received the corresponding treatment for4weeks. After4weeks, the myocardial tissue of experimental rabbits were separated under anesthesia, and Western Blot test JNK total protein and p-JNK protein. RT-PCR test expression of JNK mRNA.3.ResultsAfter intervention of ADR, each experimental rabbit myocardial P-JNK expression rise in different degree; the model control group and the DMSO model group increased most significantly (P<0.05). Compared with model control group,JNK low,high dose and positive control group myocardial P-JNK expression level increase slowly (P<0.05), the JNK high dose group myocardial P-JNK levels increase more slowly (P<0.05). The total protein of JNK, JNK mRNA expression of all the experimental groups was no significant difference (P>0.05).4.Conclusion Low-dose subcutaneous injection of JNK signaling pathway inhibitor for four weeks can significantly lower the expression of p-JNK.Part two:Base on the application method of JNK signal pathway inhibitor to explore the effect of WenYangZhen Shuai granules on JNK expression in the myocardial tissue and myocardial apoptosis in the rabbit model of chronic heart failure1.ObjectiveTo explore the effect of WenYangZhen Shuai granules on JNK expression in the myocardial tissue and myocardial apoptosis in the rabbit model of chronic heart failure.2.MethodsThe56New Zealand rabbits were randomly divided into8groups:control group, model control group, high dose JNK group, JNK blank group, high dose DMSO group, DMSO blank group, WenYangZhen Shuai group,positive control group. All the experimental groups received the corresponding treatment for8weeks. The8th weeks to investgate the dffects of wenyangzhenshuai granules on serunm NT-proBNP,JNK expression,myocardial apoptosis and myocadial ultrastructure.3.Result(1)comparison of serum NT-proBNP in each group:After intervention with Adriamycin,the concentration of serum NT-proBNP were increased,and compared with the normal control group,the difference was statistically significant (p<0.05);the pure inhibitor and the pure DMSO group compared with the normal control group had on difference (p>0.05);the high concentration of DMSOgroup compared with the model control group had on difference (p>0.05);and the high concentration of inhibitor, WenYangZhen Shuai and the positive control group compared with model control group was statistically significant (p<0.05); and serum NT-proBNP of Inhibitor high concentration group was lowest(p<0.05), and the WenYangZhen Shuai and positive control group has no significant difference (p>0.05).(2) comparison of JNK expression in each group:After intervention with Adriamycin,the myocardial p-JNK levels was increased in different degree and higher than normal control group (P<0.05); p-JNK levels of the high concentration of inhibitor, WenYangZhen Shuai and the positive control group is lower than the model control group (P<0.05),and the the high concentration of inhibitor is the lowest (P<0.05),and the WenYangZhen Shuai and positive control group has no significant difference (p>0.05);the pure inhibitor and the pure DMSO group compared with the normal control group had on difference (p>0.05);the high concentration of DMSOgroup compared with the model control group had on difference (p>0.05); The total protein of JNK, JNK mRNA expression of all the experimental groups was no significant difference (P>0.05).(3)comparison of apoptosis index in each group:After intervention with Adriamycin,the apoptosis index were increased,and compared with the normal control group,the difference was statistically significant (p<0.05);the pure inhibitor and the pure DMSO group compared with the normal control group had on difference (p>0.05);the high concentration of DMSOgroup compared with the model control group had on difference (p>0.05);the high concentration of inhibitor, WenYangZhen Shuai and the positive control group compared with model control group was statistically significant (p<0.05), and the apoptosis index of Inhibitor high concentration group was lowest(p<0.05), and the WenYangZhen Shuai and positive control group has no significant difference (p>0.05).(4)result of optical microscopy:the myocardial structure of expermental control group and drug intervention group,which had muscle fiber fracture and myocardial cell edema or inflammatory cells infiltration.The myocardial pathological changes in the high concentration of inhibitor, WenYangZhen Shuai and the positive control group was better than the model controll and The high concentration of DMSO group.(5)result of electron microscopy:In the model control and high concentration of DMSO group,the muscle fiber were necrosis or atrophy,mitochondria edema and vacuolization,filament structure is also not clear and with inflammatory cells infiltration.The myocardial pathological changes in the WenYangZhen Shuai, the concentration of the inhibitor group, positive control group were better than other groups.4.Conclusion(1)wenyangzhenshuai granule can effectively improve the heart function and reduce the concentration of serum NT-proBNP.(2)wenyangzhenshuai granule can effectively against myocardial apoptosis and improve myocardial remodeling.(3)wenyanzhenshuai granule can delay the cardiac structure changes and improve the ultrastructure of myocardial tissue,it can also partly inhibit ventricular remodeling.(4) wenyangzhenshuai granule can inhibit myocardial p-JNK expression,but no significant impact on myocardial JNK and JNKmRNA levels. |
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