野百合碱致右心衰竭幼鼠Connexin43的变化及卡托普利和坎地沙坦的干预作用  

Changes of Connexin43 in Juvenile Rats with Right Heart Failure Induced by Monocrotaline and Intervention Effects of Captopril and Candesartan

作　　者：张军毅[1] 安金斗[1] 梁芳[2] 葛薇[1] 冯嵩[1] 

机构地区：[1]郑州大学第一附属医院儿内科,郑州450052 [2]江门市中心医院儿内科,广东江门529000

出　　处：《实用儿科临床杂志》2011年第1期28-31,共4页Journal of Applied Clinical Pediatrics

基　　金：河南省医学科技攻关和临床应用技术研究项目(200716602)

摘　　要：目的探讨Connexin43(Cx43)在野百合碱(MCT)致右心衰竭幼鼠中的变化及卡托普利和坎地沙坦的干预作用。方法 50只SD幼鼠腹腔注射MCT诱发肺动脉高压(PAH),随机分为心衰4周组(E1组)、心衰6周组(E2组)、卡托普利组(C1组)、坎地沙坦组(C2组)和二药联合组(C3组)。另20只幼鼠腹腔注射9g.L-1盐水作为对照,分为正常对照4周组(N1组)和正常对照6周组(N2组)。测定每组存活幼鼠的血流动力学和相关生理指标,采用ELISA法检测其血清Cx43水平,免疫组织化学法和RT-PCR法测定其右心室心肌组织Cx43和Cx43mRNA的表达。结果 E1组与N1组比较,右心室肥厚指数、中心静脉压(CVP)、右心室收缩压(RVSP)显著升高,右心室压最大上升速率(RVdp/dt)显著降低,右心室心肌细胞排列紊乱、肌浆溶解,并可见空泡变性,右心衰竭模型成功。E1组血清Cx43水平、右心室心肌组织Cx43和Cx43mRNA均较N1组降低。E2组与N2组比较,CVP、RVSP显著增高,RVdp/dt显著降低,血清Cx43水平、右心室心肌组织Cx43蛋白和Cx43mRNA均降低。E2组与E1组比较,右心室肥厚指数、CVP、RVSP持续增高,RVdp/dt持续降低,E2组血清Cx43、右心肌组织Cx43蛋白和Cx43mRNA进一步降低。C1组、C2组与E2组比较,血流动力学改善,右心室肥厚减轻,血清Cx43水平、右心肌组织Cx43蛋白和Cx43mRNA均增高。C1组、C2组分别与C3组比较,血流动力学、血清Cx43水平、右心室心肌组织Cx43蛋白和Cx43mRNA表达比较差异均无统计学意义。结论 PAH致右心衰竭时,Cx43参与心力衰竭的发生发展,随着心力衰竭的加重,其表达进一步降低;Cx43在幼鼠血清、右心室心肌组织中的水平具有一致性;卡托普利或坎地沙坦可能通过促进Cx43的表达缓解压力负荷性右心衰竭,二者比较无明显差异,联合用药并不能提高疗效。Objective To explore the changes of connexin43（Cx43） in serum and its expression in right ventricular myocardium of juvenile rats with right heart failure induced by monocrotaline（MCT） and the intervention effects of captopril and candesartan on them.Me-thods Fifty juvenile SD rats were injected in belly cavity with MCT to induce pulmonary artery hypertension（PAH）,and they were randomly divided into 5 groups：heart failure 4 weeks group（group E1）,heart failure 6 weeks group（group E2）,captopril group（group C1）,candesartan group（group C2） and combination group（group C3）.Other 20 rats which were taken as controls were injected with 9 g.L-1saline in the belly cavity and were divided into normal control 4 weeks group（group N1） and normal control 6 weeks group（group N2）.The blood dyna-mics,myocardial weight analysis of survival rats in each group were measured and the myocardial morphology was also observed.Cx43 in se-rum was measured by enzymelinked immunosorbent assay,Cx43 and Cx43 mRNA in right ventricular myocardium were measured by immunohistochemistry and reverse transcriptase polymerase chain reaction methods,respectively.Results At 4 weeks,right ventricular hypertrophy index[RV/（LV＋S）],central venous pressure（CVP）and right ventricular systolic pressure（RVSP） increased and right ventricular pressure maximum upstroke velocity（RVdp/dt） decreased significantly in group E1 compared with those in group N1.The indiscriminate arrangement of right ventricular myocardium,solution of myoplasm and vacuolar degeneration were observed and the model of right heart failure was successfully formed.Cx43 in serum,Cx43 protein and Cx43 mRNA in right ventricular myocardium decreased in group E1 compared with those in group N1.Compared with group N2,CVP,RVSP increased and RVdp/dt decreased significantly,Cx43 in serum,Cx43 protein and Cx43 mRNA in right ventricular myocardium decreased in group E2.Compared with group E1,RV/（LV＋S）,CVP,RVSP increased and RVdp/dt decreased

关 键 词：右心衰竭 CONNEXIN43 卡托普利 坎地沙坦 野百合碱 幼鼠 

分 类 号：R541.6[医药卫生—心血管疾病]