Dissertation
Dissertation > Medicine, health > Internal Medicine > Heart, blood vessels ( circulatory ) disease > Heart disease > Myocardial diseases > Myocardial infarction

Study of Myocardial Extracellular Matrix Remodeling and Drugs Interference in Rats after Myocardial Infarction

Author ZuoZhong
Tutor WuQingLing
School Chongqing Medical University
Course Internal Medicine
Keywords myocardial infarction extracellular matrix heart function transforming growth factor-β1 transforming growth factor β receptor angiotensin converting enzyme inhibitor angiotension II receptor antagonist
CLC R542.22
Type Master's thesis
Year 2002
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Background and Objective Myocardial infarction (MI) which leads to cardiac remodeling, thinning of the ventricle wall, ventricular dilatation, myocardium hypertrophy and heart failure, is a leading cause of death. Interactions between the cardiac myocytes and the extracellular matrix (ECM) help maintain myocyte alignment required for the structural and functional integrity of the heart. Expression of ECM is regulated by a variety of physiologic signals. Prevention of the process of ECM remodeling after MI may improve the final outcome of MI and eventually, myocardial function . But there were few reports which had focus on ECM expression at infarcted zone(IZ)and non-infarcted zone (NIZ).Therefore this study would make an approach as following:1) to investigate ECM remodeling and changes of heart function in rat model of MI at different time;2)to investigate the expression of TGF-β1 and receptors proteins in IZ and to understand the relationship of TGF-β1 and ECM remodeling ;3)to investigate the effect of Enalapril 、Losartan and Losartan/Hctz on ECM remodeling and heart function in rats with MI. <WP=10>Methods The rat model of myocardial infarction was produced by left anterior decending coronary artery ligation。In sham-operated rats (S groups), the suture was passed but not tied. 2) The haemodynatics was measured by catheter measuring at 3,7,14,28,56 days after operation. 3) The levels of plasma AngII and NIZ myocardium AngII and plasma ALD wered determined through radioimmunoassay method at 7,56days after operation. 4)Expression changes of ECM components( include Col I、Col III、FN、LN) and TGF-β1、TGFβRI、TGFβRII proteins were investigated by immuno-hischemistry and image analysis. The ratio of Col I /III was also studied. 5) H.E staining and Picrosirius Red (PSR) staining were performed to determine the changes of morphology of MI. And the ultrastructures of myocardium were observed by electron microscope. Another MI rats were randomly divided into following groups:MI rats without the treatment (MI groups), MI rats treated with Enalapril 5mg·kg-1·d-1 (E groups), MI rats treated with Losartan 20mg·kg~-1·d~-1 (L groups),MI rats treated with Losartan/hctz 20mg·kg~-1·d~-1 (L/H groups) .The above indexes were observed again at 7,56 days after treatments,except of expression changes of TGF-β1、TGFβRI、TGFβRII proteins in MI and L groups.Results:1) Contents of Col I and Col III in IZ and NIZ increased gradually with time and were higher at 3,7,14,28and 56d than those in sham group at corresponding time (P<0.05, 0.01). The increase of Col I in IZ was higher in whole phase. While in NIZ, the increase of Col III was dominant in earlier phase and Col III was higher in later phase. The ratio of Col I/III in IZ and NIZ were also increased. Cardiac expressions of Col I, Col III proteins and the ratio of Col I/III were remarkely decreased in E groups, L groups; L/H groups (P<0.05,P<0.01) compared with those in 7,56 d groups after MI. There was no difference among the 3 drugs during in the later phase after MI. 2) Expressions of LN and FN proteins <WP=11>in IZ rised significantly during the time from 3th day to 14th day after MI, and rised steadily after 28 days. They were higer than those in sham group and lowed significantly when Enalapril or Losartan or Losartan/Hctz was given to rats. 3) The levels of plasma AngII and ALD increased at 7d、56 d and were higher than those in sham group(p<0.05), so did myocardium AngII in NIZ at 56d. Compared with MI groups, both Losartan and Losartan/Hctz increased the levels of plasma and AngII and plasma ALD at 56d after MI (P<0.05,P<0.01), while Enalapril decreased (P<0.05,P<0.01). 4) TGF-β1、TGFβRI、TGFβRII are associated with ECM remodeling following MI. Expressions of TGF-β1、TGFβRI、TGFβRII in IZ and NIZ sharply increased and higher than those in sham group(P<0.05,P<0.01),and were remarkely decreased in L groups. Correlative analysis revealed that TGF-β1 was positively correlated with Col I、Col III in IZ (r1=0.845,

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