| | | | | 贝那普利及依贝沙坦对大鼠心肌纤维化的作用 | | | 孔一慧;张蕾;张美;李为民;杨宝峰;刘玉冰;曹荣元;杨树森;薛竞宜;李宝馨 | | | 目的研究血管紧张素转换酶抑制剂(angiotensin converting enzyme inhibitor,ACEI)和血管紧张素Ⅱ受体拮抗剂(angiotensin II receptor blocker,ARB)对心肌梗死(myocardial infarction,MI)后大鼠结缔组织生长因子(connective tissue growth factor,CTGF)和纤溶酶原激活抑制物-1(plasminogen activator inhibitor-1,PAI-1)表达及胶原沉积的影响。方法通过冠状动脉结扎建立wistar大鼠MI模型,分为假手术组(n=9),安慰剂组(n=6),ACEI组[贝那普利10mg/(kg.d)n=8],ARB组[依贝沙坦50mg/(kg.d),n=8]和ACEI+ARB组[贝那普利10mg/(kg.d)+依贝沙坦50mg/kg.d,n=8),于术后8周处死大鼠,行心脏超声检查、检测胶原含量、分别采用逆转录多聚酶链反应和Western blot检测大鼠心肌转化生长因子β1(transforming growth factorβ1,TGFβ1)、CTGF、PAI-1mRNA和蛋白的表达。采用方差分析和Turkey's检验进行统计学分析。结果(1)与假手术组比较,安慰剂组射血分数和短轴缩短率明显降低,左室舒张末直径和E/A升高(均为P<0.01);与安慰剂组比较,ACEI组、ARB组和ACEI+ARB组射血分数(P<0.01)和短轴缩短率(P<0.05)升高,左室舒张末直径和E/A降低(P<0.05)。(2)与假手术组比较,安慰剂组的心室重量/体重和胶原总量显著升高(P<0.01);与安慰剂组比较,ACEI组、ARB组和ACEI+ARB组重量/体重下降(P<0.05),胶原总量明显降低(P<0.01);与ACEI组比较,ARB组和ACEI+ARB组胶原总量降低更为显著(P<0.01)。(3)与假手术组比较,安慰剂组TGFβ1、CTGF、PAI-1基因mRNA、蛋白表达明显升高(mRNA为0.69±0.07,0.60±0.07和0.61±0.06,P<0.01;蛋白为9.07±0.63,0.58±0.06,1.03±0.07,P<0.01),ACEI组,ARB组和ACEI+ARB组可降低这三种基因表达,联合用药较ACEI和ARB单药治疗更有效地降低mRNA基因表达;与ACEI组比较,ARB组和ACEI+ARB组降低蛋白表达更为显著。结论在心肌纤维化过程中,CTGF和PAI-1对细胞外基质过量沉积起主要作用,贝那普利和依贝沙坦通过抑制此作用阻止纤维化发生。与单用贝那普利相比,依贝沙坦单独用药和二者联合应用对阻止心肌纤维化更有效。
【作者单位】：哈尔滨医科大学附属第一医院心内科;哈尔滨医科大学附属第一医院心内科;哈尔滨医科大学附属第一医院心内科;哈尔滨医科大学附属第一医院心内科;哈尔滨医科大学附属第一医院药学院;哈尔滨医科大学附属第一医院心内科;哈尔滨医科大学附属第一医院心内科;哈尔滨医科大学附属第一医院心内科;哈尔滨医科大学附属第一医院心内科;哈尔滨医科大学附属第一医院药学院
【关键词】：纤溶酶原激活物抑制剂-1;结缔组织生长因子;心肌纤维化;贝那普利;依贝沙坦
【基金】：黑龙江省科技厅国际合作项目(WC03302);黑龙江省卫生厅基金(2006-10)
【分类号】：R96
【DOI】：CNKI:SUN:JJYZ.0.2007-08-015
【正文快照】：
交感神经活性增强和局部血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)激活可介导心肌肥大和纤维化,导致心室扩大及心律失常的发生[1]。血管紧张素转换酶抑制剂(angiotensin converting enzymeinhibitor,ACEI)和血管紧张素Ⅱ受体拮抗剂(angiotensinⅡreceptor blocker,ARB)可减轻心肌梗死后心室重塑,防止心衰及心肌纤维化的发生。已有研究证明,ACEI和ARB能抑制心脏重塑和心肌纤维化,保护心功能,提高患者的存活率。转化生长因子β1(transforming growth factorβ1,TGFβ1),结缔组织生长因子(connective tissue growth factor,CTGF)、纤溶酶原… | | |  推荐 CAJ下载  PDF下载 | | | CAJViewer7.0阅读器支持所有CNKI文件格式，AdobeReader仅支持PDF格式 | | | | Effects of benazepril and irbesartan on cardiac fibrosis in rats | | | KONG Yi-Hui;ZHANG Lei;ZHANG Mei;LI Wei-Min;YANG Bao-feng;LIU Yu-bing;CAO Rong-yuan;YANG Shu-sen;XUe Jing-yi;LI Bao-xin Department of Cardiology;The First Clinical college of Harbin Medicine University;Harbin 150001;China | | | Objective To determine the effects of both angiotensin converting enzyme inhibitor (ACEI) and angiotensin Ⅱ receptor blocker (ARB) on inhibiting connective tissue growth factor(CTGF) and plasminogen activator inhibitor-1(PAI-1) so as to control collagen accumulation in rat model with myocardial infarction(MI). Method MI was induced by ligation of the coronary artery in Wistar rats.All rats were divided into:sham operation group(n=9);control group(n=6);ACET group n=8,treated with benazepril 10 mg/(kg·d);ARB group (n=8)treated with irbesartan 50 mg/(kg·d); ACEI+ARB group (n=8) MI treated with benazepril 10 mg/(kg·d) and irbesartan 50 mg/(kg·d). After 8 weeks, parameters,namely content of collagen,mRNA and protein expression of TGF β1, CTGF and PAI-1 in myocardium were measured by reversing transcriptase- polymerase chain reactions and Western blot technique,and echocardiographic findings observed as well. All data were presented in (x±s). One-way ANOVA and Turkey's test were applied to comparing differences between groups. Results (1) Ejection fraction and shortening range of the short axis of heart were significantly decreased,and left ventricle end-diastolic transverse length and ratio of E-wave to A-wave velocity were significantly higher in control group compared with those in sham group (P<0.01). ACEI, ARB and ACEI+ARB treated groups ameliorated these of parameters measured. (2) Ventricle weigh/body weigh(VW/BW)ratio and collagen were higher in control group compared with those in sham operation group (P<0.01). ACEI, ARB and treated groups attenuated the ratio of VW/BW and collagen in comparison with those in control group (P<0.01). ARB and ACEU+ARB treated groups showed greater effect of reducing collagen deposition and the ratio of VW/BW than those in ACEI treated group(P<0.01). (3)TGFβ1 , CTGF and PAI-1 expression were markedly higher in control group compared with those in sham operation group(mRNA:0.69±0.07, 0.60±0.07,0.61±0.06 P<0.01;protein:9.07±0.63,0.58±0.06,1.03±0.07,P<0.01). ACEI,ARB and ACEI+ARB treated groups reduced the TGF-β,CTGF and PAI-1 expressions. Furthermore, ACEI+ARB treated group was proved to be more effective regarding the reduction of TGF-β1 , CTGF and PAI-1 mRNA expression than ACEI treated group or ARB treated group. ARB and ACEI+ARB treated groups in respect of decrease in the expression of protein was proved to be more effective than ACEI treated group.Conclusion These results suggest that benazepril or irbesartan is capable of ameliorating cardiac fibrosis after MI. CTGF and PAI-1 may play a crucial role in the accumulation and degradation of excessive extracellular matrix during cardiac fibrosis, and benazepril or irbesartan may be an effective agent to prevent cardiac fibrosis through preventing the expression of CTGF and PAI-1. The irbesartan and ACEI+ treatments are more effective than benazepril alone.
【Keyword】：PAI-1;CTGF;Myocardial fibrosis;Benazepril;Irbesartan |
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