螺内酯对心力衰竭大鼠心功能及血浆TGF-β-1、BNP、TNF-α的影响

The Effects of Aldactone on the Myocardial Function and the Level of Plasma TGF-β1, BNP, TNF-α in Rats

作者: 专业:内科学 导师:张金盈 年度:2010  院校: 郑州大学

Keywords

adriacin, Aldactone, heartfailure, BNP, TGF-β1, TNF-α, myocardial fibrosis
        背景慢性充血性心力衰竭是各种心脏病发展的终末阶段,也是其主要的死亡原因。大量的临床研究已经证实,血管紧张素转换酶抑制剂(ACEI)和p受体阻滞剂能够逆转心室重构,改善心功能,减少猝死,改善患者预后。螺内酯作为醛固酮受体拮抗剂,已经有研究显示其能够通过阻断醛固酮来发挥其抑制心肌纤维化,改善心功能的作用。临床上已经开始将小剂量螺内酯用于心衰的治疗中。目的研究螺内酯对阿霉素所致慢性心力衰竭大鼠心功能及血浆TGF-β1、TNF-α、BNP的影响。材料方法wistar雄性大鼠50只,随机分为3组:(1)心衰模型组(CHF,n=20):给予阿霉素(ADR)4mg/kg,腹腔注射,每周1次,持续6周,(2)心衰模型+螺内酯治疗组(HFA, n=20):给予阿霉素(ADR)4mg/kg,腹腔注射,每周1次,持续6周,同时螺内酯20mg/kg/d溶于2ml生理盐水灌胃6周,(3)正常对照组(CON, n=10):给予等体积的生理盐水。于实验第6周,检测超声心动图及血流动力学评价其心功能,测定血浆脑钠肽(BNP),转化生长因子β1(TGF-β1),肿瘤坏死因子α(TNF-α), HE染色观察心肌的组织学变化。结果(1)6周时,螺内酯组(HFA)大鼠死亡率为25%,心衰模型组(CHF)大鼠死亡率50%。(2)与正常对照组(CON)相比,心衰组(CHF)大鼠血浆BNP, TGF-β1,TNF-α明显升高,(P<0.01),螺内酯组(HFA)较心衰模型组(CHF)降低(P<0.01)。(3)超声心动图结果:螺内酯组(HFA)LVEF较心衰模型组(CHF)明显增加(p<0.01), LVESD、LVEDD较心衰组明显降低(P<0.01)。(4)血流动力学结果:螺内酯组(HFA) MAP、+dp/dtmax较心衰模型组(CHF)明显升高(P<0.01), LVEDP明显降低(P<0.01)。(5)病理学结果证实心衰模型组(CHF)符合心肌病样改变,而螺内酯治疗组(HFA)心肌病变明显减轻。结论:(1)螺内酯治疗可明显降低心衰大鼠血浆BNP、TGF-β1、TNF-α水平。(2)螺内酯可使心衰大鼠心功能明显改善。(3)螺内酯可明显改善心衰血流动力学。(4)螺内酯能减轻心力衰竭大鼠心肌纤维化。
    Background Chronic heartfailure,developed from various heartdiseases,is the main reason for death. A large number of clinical studies have confirmed that, ACEI and P-blockers can reverse left ventricular remodeling and improve cardiac function, reduce sudden death,thus improve the prognosis of patients.aldactone,a Aldosterone receptor antagonist,has shown its ability by blocking the aldosterone to inhibit myocardial fibrosis and improve cardiac function in some studies. Low-dose aldactone has been added to the treatment of heartfailure during the clinical practice.Objective To study the effect of aldactone on the cardiac function of congestive heart failure rats,and the effect on the level of plasma BNP.TGF-β1.TNF-α.Methods 50 healthy male wistar rats were randomly divided into three groups: Chronic heart failure group(CHF.n=20),Aldactone group(n=20) and control group (n=10).The CHF group rats were given ADR 4mg/kg per week intraperitoneally in 6 weeks.Aldactone group rats were given the same doze ADR, at the same time aldactone 20mg/kg/d were given for 6 weeks.Control group rats were given an equal volume saline.6 weeks later,echocardiography and hemodynamics were taken to evaluate the cardiac function.Taking blood to test the concentration of plasma BNP.TGF-β1.TNF-α. Staining the myocardial tissue to view the differences of different group. Results(1)at the end of 6th week,25% of the aldactone group rats died of congestive heart failure in contrast with 50% of the CHF group.(2)Compared with the control group,the level of plasma BNP.TGF-β1.TNF-αin CHF group increased significantly(p<0.01).the aldactone group showed a lower level of plasma BNP,TGF-β1 and TNF-αcompared with the CHF group(p<0.01).(3)The MAPand+dp/dtmax of the aldactone group rats were much higher than the CHF group(p<0.01).and aldactone group showed a lower LVEDP compared with the CHF group(p<0.01).(4)Compared with the CHF group,the LVESD,LVEDD of the aldactone group decreased significantly (p<0.01).(5)The pathology results showed a cardiomyopathy changes in the CHF group,much more severe than the aldactone group.Conclusion(1) Aldactone can reduce the level of plasma BNP,TGF-β1,TNF-αsignificantly.(2)Aldactone can improve the myocardial function.(3)Aldactone can improve the results of hemodynamics in heartfailure rats.(4)Aldactone can alleviate the myocardial fibrosis.
        

螺内酯对心力衰竭大鼠心功能及血浆TGF-β-1、BNP、TNF-α的影响

摘要4-6
Abstract6-7
引言9-11
1 材料和方法11-14
    1.1 实验材料11
    1.2 动物分组及模型的制作11
    1.3 超声心动图检查11-12
    1.4 血流动力学测定12
    1.5 血浆BNP,TGF-β1,TNF-α测定12-13
    1.6 苏木精和伊红染色(HE染色)13-14
2 统计学分析14-15
3 结果15-19
4 讨论19-23
参考文献23-26
综述26-50
    参考文献43-50
缩略词50-51
致谢51-52
个人简历52
        下载全文需18


本文地址:

上一篇:河南汉族人群纤维蛋白原β-148C/T基因多态性及血浆Fg、白细胞介素-6水平与冠心病相关性
下一篇:血清OPG、sRANKL水平与冠心病的相关性研究

分享到: 分享螺内酯对心力衰竭大鼠心功能及血浆TGF-β-1、BNP、TNF-α的影响到腾讯微博           收藏
评论排行
频道总排行
频道本月排行