Ghrelin对慢性充血性心力衰竭兔三层心肌间Cx43表达的影响  

Effect of Ghrelin on the expression of Cx43 in three layers in rabbit with chronic congestive heart failure

作　　者：李思瑶 陆士娟[1] 吴美霞 吴淼[1] 马添翼[1] 李强 张伟 黄康[1] 钟江华[1] LI Siyao;LU Shijuan;WU Meixia;WU Miao;MA Tianyi;LI Qiang;ZHANG Wei;HUANG Kang;ZHONG Jianghua(Department of Cardiology,Haikou Hospital Afiliated to Xiangya School of Medicine,Central SouthUniversity,Haikou 570208,China)

机构地区：[1]中南大学湘雅医学院附属海口医院心内科,海南海口570208

出　　处：《沈阳药科大学学报》2021年第2期170-178,共9页Journal of Shenyang Pharmaceutical University

基　　金：国家自然科学基金资助项目(81660057)。

摘　　要：目的观察生长激素释放肽(ghrelin)对慢性充血性心力衰竭(chronic congestive heart failure,CHF)兔左心室三层心肌间跨室壁缝隙连接蛋白43(connexin43,Cx43)表达的影响,为CHF恶性室性心律失常(malignant ventricular arrhythmia,MVA)的防治寻找新的靶点。方法将40只新西兰大白兔随机分成假手术组(Sham组,n=20)和CHF组(n=20)。CHF组通过缩窄腹主动脉构建CHF模型,sham组开腹未结扎。术后同等条件喂养8周,在体检查超声心动图比较两组兔左心室舒张末期内径(left ventricular end-diastolic diameter,LVEDD)、左室后壁厚度(left ventricular posterior wall thickness,LVPW)和左室射血分数(left ventricular ejection fraction,LVEF);在体血流动力学检查比较两组心率(heart rate,HR)、外周动脉收缩压(peripheral arterial systolic pressure,SBP)、舒张压(diastolic blood pressure,DBP)、平均动脉压(mean arterial pressure,MAP)、左心室最大上升速度和最大下降速度(±dp/dtmax)等参数。饲养8周后将Sham组分成Sham台式液灌流亚组、Sham Ghrelin灌流亚组,CHF组分成CHF台式液灌流亚组、CHF ghrelin灌流亚组,处死兔制作左心室心肌Masson染色图片,分别给予正常台式液及ghrelin对CHF组及Sham组的心脏灌流,分别切取左心室心内膜下心肌(endometrium,endo)、中层心肌(middle,mid)、心外膜下心肌(epicordium,Epi),采用RT-PCR、Western blot检测各组左心室三层心肌间Cx43mRNA(Cx43-Cq)、Cx43蛋白(Cx43-pro)的表达,并计算三层心肌间最大Cx43-pro与最小Cx43-pro之差(ΔCx43-pro)以及最大Cx43-Cq与最小Cx43-Cq之差(ΔCx43-Cq)。结果与Sham组相比,CHF组P、SBP、DBP、MAP明显升高,LVEF明显下降(P<0.05)。与Sham台式液灌流亚组相比,CHF台式液灌流亚组三层心肌的Cx43蛋白及mRNA的表达明显降低(P<0.05)。CHF组内相比,CHF Ghrelin灌流亚组的Cx43蛋白及mRNA的表达明显高于CHF台式液灌流亚组,而△Cx43-pro及△Cx43-Cq显著低于CHF台式液灌流亚组(P<0.05)。结论Objective To observe the effect and significance of Ghrelin on the expression of connexin43(Cx43) in three layers of left ventricular myocardium in rabbit with chronic congestive heart failure(CHF).Methods Forty New Zealand white rabbits were randomly divided into sham operation group(Sham group,n=20) and CHF group(n=20).In the CHF group,the CHF model was constructed by narrowing the abdominal aorta,and the sham group was not ligated.After 8 weeks of feeding,the left ventricular end-diastolic diameter(LVEDD),left ventricular posterior wall thickness(LVPW) and left ventricular ejection fraction(LVEF) were compared by in vivo echocardiography between the two groups.The heart rate(HR),peripheral arterial systolic pressure(SBP),diastolic blood pressure(DBP),mean arterial pressure(MAP),left ventricular maximum ascending velocity,and maximum descending velocity(±dp/dtmax) were assessed by haemodynamic measurements between the two groups.After 8 weeks of feeding,the Sham components were divided into Sham tyrode perfusion subgroup,Sham Ghrelin perfusion subgroup,CHF fraction into CHF tyrode perfusion subgroup,CHF Ghrelin perfusion subgroup,and rabbits were sacrificed to make left ventricular myocardial Masson staining images,respectively.Left ventricular endocardial(Endo),middle myocardium(Mid),and subepicardial myocardium(Epi) were excised from the heart and spleen of CHF group and Sham group,Expressiom levels of Cx43 protein(Cx43-pro)and mRNA(Cx43-Cq) in all three layers and the difference between the maximum Cx43-pro and the minimum Cx43-pro between the three layers of myocardium(ΔCx43-pro) and the maximum Cx43-Cq and minimum The difference between Cx43-Cq(ΔCx43-Cq) were measured by Western blotting and RT-PCR.Results Compared with Sham group,P,SBP,DBP and MAP in CHF group were significantly increased,LVEF were significantly decreased(P<0.05).Compared with the Sham tyrode perfusion subgroup,the expression of Cx43-pro and Cx43-Cq in the three layers myocardium of CHF tyrode perfusion subgroup was significantly lower

关 键 词：慢性充血性心力衰竭 中层心肌细胞 连接蛋白43 生长激素释放肽 恶性室性心律失常 

分 类 号：R94[医药卫生—药剂学]