Paeonol Inhibit Ventricular Remodeling After Myocardial Infarction In Rats And The Impact On The RAS

Objective:To establish rat model of myocardial infarction through ligate the left anterior descending coronary artery of rats. Using HE staining method and masson staining to observe the effection of paeonol on changes of cardiac lesions and the degree of myocardial fibrosis of the rats that occurred in ventricular remodeling after MI; Using the method of Real-Time PCR and Western blot to observe the influence of paeonol on RAS of rats from the gene and protein level, to discuss the molecular mechanisms of paeonol effect on heart function after MI in rats.Methods:1.Rats’ left anterior descending coronary artery was ligated to establish the model of myocardial infarction.2.Hematoxylin-eosin staining was used to observe the pathological changes of cardiac tissue.3.Masson staining was used to observe the degree of myocardial fibrosis.4.Real-Time PCR was used to detect the expression of AGT, AGTR1 and ET-1 mRNA of rats in each group5.Western blot was used to detect the expression of Ang-Ⅱ、ACE、AGTR1 of rats in each groupResults:1.After ligated the rats’ left anterior descending coronary artery, myocard under the ligature colored white; ST-segment elevated obviously.2.HE staining showed that the shame-operated group’s cardiac tissue has clear stripes, regular and complete arrange, nucleus were visible clearly and cytoplasm was uniform and rich; compared with shame-operated group, myocardial cells in model group arranged in disorder and occurred cell hypertrophy and nucleus deletion and myocardial fiber breakage; compared with model group, paeonol low, medium, high dose group and captopril control group improved myocardial pathological state in different degrees, the affection is between shame-operated group and model group. The high-dose group of paeonol is the best, comparable to captopril control group.3.Masson staining showed that, there is on significant breakage of myocardial tissue in shame-operated group and the myocardial cells were tightly packed. Compared with shame-operated group, collagen fibers of rats is significantly increased and replace the normal myocardial tissue in model group, damaged the normal structure of myocardial tissue; compared with model group, the situation of fibrosis in paeonol low, medium, high dose group and captopril control group has reduced and the affection is between shame-operated group and model group. The high-dose group of paeonol is the best, comparable to captopril control group.4.Real-Time PCR showed that the transcription of AGT, AGTR1, ET-1 mRNA in model group is significantly increased compared with shame-operated group(P<0.01). Compared with model group, the expression of those also obviously decreased in paeonol high dose group and captopril control group(P<0.01); the expression of AGT is significantly decreased in middle-dose group of paeonol(P<0.01), the expression of AGTR1 also decreased(P<0.05),the difference has statistical significance, the expression of ET-1 has no obviously change, the difference has no statistical significance(P>0.05); except the expression of AGT is significantly decreased in low-dose group of paeonol(P<0.01), the expression of AGTR1 and ET-1 has no obviously change, the difference has no statistical significance(P>0.05).5.Western blot analysis show that the transcription of AGTR1, Ang-Ⅱand ACE protein in model group were obviously higher than shame-operated group(P<0.01).Compare with model group, the transcription of AGTR1 in low-dose group of paeonol has no obvious change, the difference has no statistical significance(P>0.05),but the transcription of Ang-Ⅱand ACE is changed, the difference has statistical significance(P<0.05); the transcription of AGTR1, Ang-Ⅱand ACE were significantly decreased, the difference has statistical significance(P<0.01).Conclusion:1.Myocardial fibrosis occurred after MI, and then occurred ventricular remodeling.Paeonol can improve the ventricular remodeling through inhibit the myocardial fibrosis.2.Paeonol probably through inhibit the expression of AGT mRNA,the expression of ACE reduce the expression of Ang-Ⅱ and ET-1, and then inhibit the excessive activation of RAS and reverse ventricular remodeling after myocardial infarction of rats.3.Paeonol probably through inhibit the expression of AGTR1; decrease the combination of Ang-Ⅱwith AGTR1, against the excessive activation of RAS, and then inhibit the ventricular remodeling after myocardial infarction of rats.