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The Effect Of Foli Acid On Left Ventricle Reconstruction In Rats With Hyperhomocysteinemia

Posted on:2019-02-19Degree:MasterType:Thesis
Country:ChinaCandidate:Q L FuFull Text:PDF
GTID:2394330545478437Subject:Department of Cardiology
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Background: ventricular remodeling plays an important role in the pathophysiology of various cardiovascular diseases.(such as hypertension,myocardial infarction,cardiomyopathy and peripheral vascular disease.)Ventricular remodeling involves remodeling of cardiac myocytes and remodeling of non cardiac myocytes.ECM is a major component of non cardiomyocytes.Its quality and quantity change cause changes in ECM composition and sequence to make ventricular remodeling.ECM is composed of a variety of active components,such as collagen,elastin and proteoglycan,among which type I and type III collagen fibers are the key components of ECM.MMP are a class of endogenous proteases containing zinc ions,which play a variety of roles in the degradation and remodeling of proteins in ECM.The study shows that HHcy affects the pathological process of ventricular remodeling [1,2],the increase of Hcy level leads to ECM degradation of myocardium,resulting in ventricular remodeling [3].Ventricular remodeling,characterized by interstitial and perivascular fibrosis,changes the ventricular compliance and is associated with the severity of chronic heart failure [4] inHHcy.Vitamin combined with folic acid can weaken the fibrosis of the myocardium and delay the process of ventricular remodeling [5].Combined treatment of folic acid and Vit B in elderly patients with chronic heart failure and HHcy can reduce serum Hcy level and improve ventricular remodeling and cardiac function [6].The impact of folic acid used alone on left ventricular remodeling is still low at home and abroad,and the mechanism needs to be further studied.Objective: Observation of HHcy rat model: 1.The effect of and HHcy on left ventricular remodeling in rats 2.The effect of folic acid on the histomorphological changes of myocardium in HHcy rats and the expression of type I collagen and type III in myocardial tissue.3.The effect of folic acid on the expression of MMP-2 and MMP-9 in myocardial tissueMethods: 30 rats were randomly divided into three groups,which were blank control group,folic acid intervention group and high methionine group,with 10 rats in each group.The blank control group was fed with ordinary feed for 16 weeks,8 weeks later,normal saline was given to the stomach once a day.The folic acid intervention group was given 2% methionine feed for 8 weeks,and then fed to the common feed for 8 weeks,8 weeks later,5mg/kg folic acid was given to the stomach,once a day.The high methionine group was fed with2% methionine feed for 8 weeks,and then fed to the common feed for 8 weeks,and was given intragastric administration of normal saline once a day.The sixteenth week of the experiment,the serum Hcy concentration of Elisa,HE staining was used to observe the changes of myocardial structure and morphology of myocardium.Masson staining was used to observe the changes of collagen fibers in rat myocardium.Immunohistochemistry was used toobserve the expression of collagen type I and type III and the expression of MMP-2 and MMP-9 in rat cardiomyocytes.Results: 1.The level of Hcy in the serum of rats in each group.At the end of 16 weeks,serum Hcy concentration in each group was measured.The concentration of Hcy in serum of control group,high methionine and folate intervention group was 11.59 + 2.61umol/L,21.63 + 3.72umol/L and16.94 + 1.31umol/L respectively.The difference between the blank control group and the high methionine group was statistically significant,and the difference between folic acid intervention group and high methionine group was statistically significant.2.1 The HE staining of rat's heart showed that the myocardial cells in the blank control group were normal,and there was no myocardial hypertrophy.In the high methionine group,the arrangement order of myocardial cells was obviously disordered,myocardial hypertrophy,interval of myocardium were widened,and the infiltration of many inflammatory cells.In the folic acid treatment group,the myocardial cells were hypertrophied,the myocardial distance was slightly wider,and the inflammatory cells were less.2.2.Masson staining of rat myocardium showed that there were few collagen fibers in the myocardium of the blank control group,and the collagen proliferation was not obvious.The collagen fibers in the myocardium of the high methionine group increased obviously,and the collagen proliferation was obvious.In the folic acid intervention group,the collagen fibers in the rat myocardium were less,the myocardial collagen proliferation was obvious.3.Expression of collagen type I and type III collagen in myocardium of ratsThe positive expression area of type I collagen in the blank control group,the high methionine group and the folic acid group was 2.49±0.29,4.45±0.53 and 3.52±0.19,respectively,P<0.05.There was significant difference between the blank control group and the high methionine group,and the difference between folic acid intervention group and high methionine group was statistically significant.The positive expression area of type III collagen in the blank control group,the high methionine group and the folic acid group was 4.23±0.21,4.14±0.42 and 4.26±0.34,respectively,P>0.05.The difference between the blank control group and the high methionine group was statistically significant,and the difference was statistically significant compared with the high methionine in the folic acid group.4.Expression of MMP-2 and MMP-9 in myocardial tissue of rats in each groupThe positive expression area of MMP-2 in the blank control group,the high methionine group and the folic acid group were 3.49±0.28,5.03±0.28 and4.03 ±0.15,respectively,P<0.05.The difference between the blank control group and the high methionine group was statistically significant,and the difference was statistically significant compared with the high methionine in the folic acid group.The positive expression area of MMP-9 in the white control group,the high methionine group and the folic acid group was 3.83±0.14,5.97±0.29 and 4.56 ± 0.40,respectively,P<0.05.The difference between the blank control group and the high methionine group was statistically significant,and the difference was statistically significant compared with the high methionine in the folic acid group.Conclusion: 1.HHcy can induce left ventricular remodeling in rats.2.folic acid can reverse the effect of left ventricular remodeling in HHcy rats andreduce the expression of type I collagen in myocardial tissue.3.the expression of MMP-2 and Matrix MMP-9 was involved in the involvement of folic acid in the left ventricular remodeling in HHcy rats.
Keywords/Search Tags:Rat, Hyperhomocysteinemia, MMP-2, MMP-9, Folic acid
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