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Pharmacodynamics And Mechanism Of Action Of Qifu Decoction And Its Disassembled Prescriptions On The Cardiotoxicity Of Adriamycin

Posted on:2012-06-12Degree:DoctorType:Dissertation
Country:ChinaCandidate:C N YuFull Text:PDF
GTID:1484303362959319Subject:Traditional Medical Formulae
Abstract/Summary:PDF Full Text Request
Purpose:To observe the general conditions, the survival rate, body weight, heart weight and radio of heart/body weight, electrocardiogram changes, myocardial histomorphological changes in the rats with adriamycin-induceded cardiotoxicity, Qi-fu Decoction was given simultaneously, the effect of Qi-fu Decoction and its decomposed recipes on the adriamycin- induceded cardiotoxicity has been demonstrated. To measure the activity and content of superoxide dismutase (SOD) and glutathione peroxidase(GSH-Px), the content of malondialdehyde (MDA), cardiomyocyte apoptosis rate, the mRNA expression of Bax, Bcl-2, P53 and Caspaes-3, which might be related with antioxidant stress and the inhibiting apoptosis of Qi-fu Decoction and its decomposed recipes on the adriamycin- induceded cardiotoxicity.Material and method:The method of injecting adriamycin(ADR) intraperitoneally was adopted to duplicat the rat model of ADR-induced cardiotoxicity. Qi-fu Decoction and its decomposed recipes were given simultaneously.besides the the normal group and the model group, fuzi water solution was given intragastrically to the rats of fuzi 1 group without duplicating ADR-induced cardiotoxicity model. Shengmai Yin was given intragastrically to the rats of Chinese herb control group, Qi-fu Decoction and its decomposed recipes--- fuzi group, Huangqi group and Qifu decoction group were taken as drug treatment groups. There were 4 weeks in administrating ADR and giving medicine, in the same tiame, the general conditions of the rats were observed. After 4 weeks, the rats were sacrificed and their hearts were removed.the indexes about the heart were measured. heart weight, radio of heart/body weight, myocardial histomorphological changes observd by light and light and electron microscopy, the activity SOD, GSH-Px and the content of MDA measured by chemical colorimetric assay, and the content of SOD,GSH-Px and MDA by Enzyme-linked immunosorbent assay,the cardiomyocyte apoptosis rate by flow cytometry., the mRNA expression of Bax, Bcl-2, P53 and Caspaes-3 by real time polymerase chain reaction.Results:1. The general condition: compared with the general condition of the normal group, that of the model group were manifested by listlessness, activity decreased, curl up lie, grabbed resistance weakened, hair without luster, accompanied depilate, blood in the mouth and nose of some rats can be obviously observed, individual occurrence of ascites, diarrhea. Compared with that of the model group, the symptoms of Chinese herb control, huangqi group, Qifu decoction group were better, that of fuzi group were worse. The general conditions of fuzi 1 group were similar to that of the normal group.2.The body weight, the heart weight and the heart index of the rats: the body weight of the rats fell much than that of the model group, with statistical significance (P?0.01). Compared with the body weight of the rats in the model group, that of control Chinese medicin group, huangqi group, Qifu decoction group were increased, with statistical significance (P?0.05),that of huangqi group is the most. the heart weight of the rats fell much than that of the model group, with statistical significance (P?0.05). Compared with the heart weight of the rats in the model group, that of control Chinese medicin group,fuzi group, huangqi group, Qifu decoction group were increased in a degree(P?0.05).the heart index of the model group is decreased slightly compared with that of the normal group (P?0.05), compared with that of the model group, there were no obvious changes in the heart index of the other groups(P?0.05). The body weight, the heart weight and the heart index of the rats in fuzi 1 group were similar to that of the normal group.3. Electrocardiogram: compared with that of the normal group, the heart rate group was slower(P?0.01), QRS volvage sum decreaced(P?0.05), Q-T interphase extended(P?0.05)of the model group, individual appeard arrhythmia. Compared with that of the model group, the heart rate was more quicker of all administrated groups, QRS volvage sum increased of huangqi group, qifu decoction group and fuzi2 group, Q-T interphase shorten of , huangqi group, qifu decoction group and chinese herb control,all with statistical significance(P?0.05). The heart rate, QRS volvage sum and Q-T interphase of the rats in fuzi 1 group were similar to that of the normal group.4.Cardiac histomorphologic chang observed by light microscope and electron microscope: Observed by light microscope, there were flocular degeneration in cardiac myocytes, myocardial gap widened, part of myocardial fiber fractured, and a few lymphocytes penetration embellished in the rats'cardiomyocytes of the model group. Observed by electron microscope, there were myocardial filaments fractured and dissolved, Z line arrangement in disorder, part of Z line dissolved, mitochondrial swelling and its crista ruptured, vacuole foumed in the cardiac myocyte of the model group. The pathological changes of the rats'cardiomyocytes of fuzi group were worse than that of the model group, Cardiac histomorphologes were improved in different degree of Chinese herb controlgroup, huangqi group and qifu decoction group. There were slight pathological chang in the rats'cardiomyocytes of fuzi 1 group.5. The activity and content of SOD of the rat's cardiac myocyte: Compared with that of the normal group, the activity is weakened, and the content is deduced of SOD of the model group, with statistical significance (P?0.05). Compared with that of the model group, SOD activity is enhanced of Chinese herb controlgroup, huangqi group and qifu decoction group, with statistical significance (P?0.05), qifu decoction group is the most, that of fuzi group is weakened (P?0.05). SOD content is increased of chinese herb control and huangqi group, with statistical significance (P?0.05).6. The activity and content of GSH-Px of the rat's cardiac myocyte: Compared with that of the normal group, the activity is weakened, and the content is deduced of GSH-Px of the model group, with statistical significance (P?0.05). Compared with that of the model group, GSH-Px activity is enhanced of chinese herb control, huangqi group and qifu decoction group, GSH-Px content is increased of all administrated group, all with statistical significance (P?0.05).7. MDA content of the rat's cardiac myocyte: Compared with that of the normal group, MDA content of the model group is increased, with statistical significance (P?0.05). Compared with that of the model group, MDA content of chinese herb control, huangqi group and qifu decoction group is decreased, with statistical significance (P?0.05).8. Apoptosis rate of cardiac myocyte: Compared with that of the normal group, apoptosis rate of the model group is increased, with statistical significance (P?0.05). Compared with that of the model group, apoptosis rate is increased of chinese herb control, fizi group, huangqi group and qifu decoction group,all with statistical significance (P?0.05).9. Bax mRNA and Bcl-2mRNA expression and Bcl-2/Bax of the myocardium of the rats: Compared with that of the normal group, BaxmRNA expression is increased, Bcl-2 mRNA expression is decreased, Bcl-2/ Bax decreased, of the model group, all with statistical significance (P?0.05). Compared with that of the model group, Bax mRNA expression is decreased of fizi group, huangqi group and qifu decoction group, Bcl-2 mRNA expression and Bcl-2/ Bax are increased of chinese herb control, huagnqi group and qifu decoction group, all with statistical significance (P?0.05).10. P53 mRNA expression of the myocardium of the rats: Compared with that of the normal group, P53mRNA expression of the model group is increased, with statistical significance (P?0.05). Compared with that of the model group, P53mRNA expression is decreased, of all administrated group, all with statistical significance (P?0.05).11. caspase-3mRNA expression of the myocardium of the rats: compared with that of the normal group, caspase-3 mRNA expression of the model group is increased, with statistical significance (P?0.05). Compared with that of the model group, caspase-3 mRNA expression is decreased, of all administrated group, all with statistical significance (P?0.05) and the huangqi group is the most. Conclusion:1.Fuzi can increase adriamycin-induced cardiotoxicity?2.Qifu decoction and Huangqi can protect the rats from adriamycin-induced cardiotoxicity?3.The mechanisms is related to antioxidant stress and inhibiting apoptosis.
Keywords/Search Tags:Qifu decoction, the decomposed recipes, adriamycin, cardiotoxicity, pharmacology
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