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Effects Of Neuregulin-1β On Angiogenesis In The Myocardial Tissue Of Myocardial Infarction Rats

Posted on:2017-12-11Degree:MasterType:Thesis
Country:ChinaCandidate:F L HeFull Text:PDF
GTID:2504306602999539Subject:Department of Cardiology
Abstract/Summary:PDF Full Text Request
Objective To explore the changes of myocardial blood flow and angiogenesis in acute myocardial infarction rats by injecting recombinant human neuregulin-1β,respectively in the infarction zone(IZ)and the border zone(BZ),and lay the foundation for exploring new prevention and treatment methods.Methods Male Sprague Dawley(SD)rats weight 200-250 g were connected the ventilator by endotracheal intubation,then ligated the left anterior descending coronary artery and if you see perfusion areas became white what were regarded as successful acute myocardial infarction rats and were divided into three group:Sham group,acute myocardial infarction(MI group),acute myocardial infarction NRG-1 treatment group(NRG-1 group).Male Sprague Dawley(SD)rats weight 200-250 g were induced by a single intraperitoneal injection of streptozotocin(STZ)at a dose of 55mg/kg.A week later,the rats with random blood glucose above 16.7mmol/L were regarded as successful diabetes rats.After,the detection of random blood glucose was once a week.A month later,some rats were randomly selected to establish the model of acute myocardial infarction,after they were randomly divided into Diabetes sham group(DS group),diabetic rats with acute myocardial infarction(DI group)and NRG-1 treatment group(DR group).After 2-4 hours,the NRG-1 group and DR group were treated with injection of rh Neuregulin-1β at a dose of 10μg/kg.d for consecutive 10 days and sham group and MI group and DS group and DI group with simultaneously administrating with 0.1mmol/L citrate buffer(PH:3.0).The cardiac function was measured by MPA cardiac function analysis system.The capillary vessels density was quantified as the number of capillaries per cardiomyocytes using CD31 immunostaining.Results:1.Compared with the sham group,the maximum left ventricular pressure(Pmax),the minimum ventricular pressure(Pmin),left ventricular mean pressure(Pmean)and the left ventricular pressure rise maximum rate(+dp/dtmax)were significantly decreased in MI group [(106.18±3.11)mm Hg vs(77.92±6.46)mm Hg,(6.94±3.44)mm Hg vs(-4.21±6.23)mm Hg,(54.26±5.12)mm Hg vs(30.43±1.80)mm Hg,(1087.65±35.06)mm Hg/s vs(887.29±184.39)mm Hg/s,P all<0.05].However,there was no markedly difference in the left ventricular pressure decreases maximum rate(-dp/dtmax)between the two groups was observed(P>0.05).The myocardial blood flow with the infarction zone(IZ)and the border zone(BZ)were significantly decreased in MI group[(8.87±3.20)ml/g.min vs(2.48±0.94)ml/g.min,(8.87±3.20)ml/g.min vs(2.22±0.97)ml/g.min,P both<0.05].However,there were no markedly difference in the ratio of capillary/myocyte(C/M)with the infarction zone(IZ)and the border zone(BZ)between the two groups were observed [(0.50±0.12)vs(0.48±0.11),(0.50±0.12)vs(0.46±0.17),P both>0.05].Compared with MI group,the maximum left ventricular pressure(Pmax),the minimum ventricular pressure(Pmin),left ventricular mean pressure(Pmean)and the left ventricular pressure rise maximum rate(+dp/dtmax)were significantly increased in NRG-1 group[(77.92±6.46)mm Hg vs(93.65±1.64)mm Hg,(-4.21±6.23)mm Hg vs(8.04±2.40)mm Hg,(30.43±1.80)mm Hg vs(45.62±4.61)mm Hg,(887.29±184.39)mm Hg/s vs(1005.60±135.06)mm Hg/s,P all<0.05].However,there was no markedly difference in the left ventricular pressure decreases maximum rate(-dp/dtmax)between the two groups was observed [(-772.81 ± 99.15)mm Hg/s vs(-835.77±37.32)mm Hg/s,P>0.05].The myocardial blood flow and the ratio of capillary/myocyte(C/M)with the infarction zone(IZ)and the border zone(BZ)respectively were increased in NRG-1 group [(2.48±0.94)ml/g.min vs(7.95±3.70)ml/g.min,(2.22±0.97)ml/g.min vs(6.89± 2.97)ml/g.min,(0.48±0.11)vs(0.57 ± 0.16),(0.46 ± 0.17)vs(0.56 ± 0.18),P all<0.05].2.Compared with DS group,the maximum left ventricular pressure(Pmax),the left ventricular pressure rise maximum rate(+dp/dtmax)and left ventricular pressure decreases maximum rate(-dp/dtmax)were significantly reduced in DI group[(65.71±2.82)mm Hg vs(50.03±2.39)mm Hg,(821.87±102.82)mm Hg/s vs(472.27±105.81)mm Hg/s,(-576.11±66.59)mm Hg/s vs(-379.25±14.31)mm Hg/s,P all<0.01].However,there were no markedly difference in the minimum ventricular pressure(Pmin),left ventricular mean pressure(Pmean)and the myocardial blood flow with the border zone(BZ)between the two groups were observed [(-0.84±1.44)mm Hg vs(1.08±2.01)mm Hg,(26.85±2.08)mm Hg vs(22.87±2.74)mm Hg,(3.60±1.45)ml/g.min vs(2.86±2.85)ml/g.min,P all> 0.05].The myocardial blood flow with the infarction zone(IZ)were significantly reduced in DI group [(3.60±1.45)ml/g.min vs(1.04±0.80)ml/g.min,P<0.01].The ratio of capillary/myocyte(C/M)with the infarction zone(IZ)and the border zone(BZ)were significantly reduced [(0.43±0.11)vs(0.26±0.15),(0.43±0.11)vs(0.26±0.11),P both <0.01].3.Compared with the sham group,the maximum left ventricular pressure(Pmax),the minimum ventricular pressure(Pmin),left ventricular mean pressure(Pmean),the left ventricular pressure rise maximum rate(+dp/dtmax)and left ventricular pressure decreases maximum rate(-dp/dtmax)were significantly decreased in DS group[(106.18±3.11)mm Hg vs(65.71±2.82)mm Hg,(6.94±3.44)mm Hg vs(-0.84±1.4)mm Hg,(54.26±5.12)mm Hg vs(26.85±2.08)mm Hg,(1087.65±35.06)mm Hg/s vs(821.87±102.82)mm Hg/s,(-875.84±62.71)mm Hg/s vs(-576.11±66.59)mm Hg/s,P all<0.01].The myocardial blood flow and the ratio of capillary/myocyte(C/M)were significantly decreased in DS group[(8.87±3.20)ml/g.min vs(3.60±1.45)ml/g.min,(0.50±0.12)vs(0.43±0.11),P both<0.01].Compared with MI group,the maximum left ventricular pressure(Pmax),left ventricular mean pressure(Pmean),the left ventricular pressure rise maximum rate(+dp/dtmax)and left ventricular pressure decreases maximum rate(-dp/dtmax)were significantly lower in DI group [(77.92±6.46)mm Hg vs(50.03±2.39)mm Hg,(30.43 ± 1.80)mm Hg vs(22.87±2.74)mm Hg,(887.29±184.39)mm Hg/s vs(472.27±105.81)mm Hg/s,(-772.81±99.15)mm Hg/s vs(-379.25±14.31)mm Hg/s,P all<0.01].The minimum ventricular pressure(Pmin)increased in DI group [(-4.21±6.23)mm Hg vs(1.08±2.01)mm Hg,P<0.05].However,there was no markedly difference in the myocardial blood flow with the infarction zone(IZ)and the border zone(BZ)respectively between the two groups were observed [(2.48±0.94)ml/g.min vs(1.04±0.80)ml/g.min,(2.22±0.97)ml/g.min vs(2.86±2.85)ml/g.min,P both>0.05].The ratio of capillary/myocyte(C/M)with the infarction zone(IZ)and the border zone(BZ)were significantly lower in DI group [(0.48±0.11)vs(0.26±0.15),(0.46±0.17)vs(0.26±0.11),P both<0.01].Conclusions 1.The myocardial blood flow with the infarction zone(IZ)and the border zone(BZ)are both reduced in acute myocardial infarction rats.The left ventricular function is weakened in acute myocardial infarction rats.2.Exogenous intervention by rh NRG-1β can impove the cardiac function in rats with acute myocardial infarction,increase myocardial blood flow with the infarction zone(IZ)and the border zone(BZ),and promote angiogenesis in both the infarction zone(IZ)and the border zone(BZ).3.The myocardial blood flow and capillary density reduced significantly in diabetic rats.The left ventricular function in diabetic rats is declined.The left ventricular function is significantly deteriorated in diabetic rats with acute myocardial infarction.The capillary density was significantly reduced in both the infarction zone(IZ)and the border zone(BZ).
Keywords/Search Tags:Neuregulin-1β, acute myocardial infarction, acute myocardial infarction with diabetes, angiogenesis, myocardial blood flow, left ventricular function
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