慢性栓塞性肺动脉高压大鼠肺动脉平滑肌电压依赖性钾通道蛋白mRNA表达的变化  

Change of voltage-dependent potassium channel protein mRNA expression of pulmonary artery smooth muscle in rats with chronic thromboembolic pulmonary hypertension

作　　者：云昕[1] 陈豫钦[1] 林纯意[1] 王健[1] 

机构地区：[1]广州医科大学附属第一医院呼吸内科 广州呼吸疾病研究所呼吸疾病国家重点实验室,510120

出　　处：《中华生物医学工程杂志》2015年第6期490-494,共5页Chinese Journal of Biomedical Engineering

基　　金：国家自然科学基金（81220108001、81470246）;广州市卫生局医药卫生科技项目（20151A011073）

摘　　要：目的 建立慢性栓塞性肺动脉高压大鼠模型,研究肺动脉结扎对大鼠肺动脉平滑肌电压依赖性钾通道蛋白Kv1.5和Kv2.1 mRNA表达的影响,探讨疾病发生发展的机制.方法 将雄性SD大鼠运用左肺动脉结扎法建立慢性栓塞性肺动脉高压大鼠模型,随机分为正常对照2周组、左肺动脉结扎2周组、假手术2周组和正常对照5周组、左肺动脉结扎5周组、假手术5周组,每组5只.直接右心测压法测6组大鼠右心室收缩压及平均压;取心脏称质量测定右心室肥厚指数;HE染色观察肺组织和肺血管结构的变化,测肺动脉相对中膜厚度（PAMT）、管壁面积/管总面积（WA/rA）;实时荧光定量PCR检测肺动脉平滑肌组织Kv1.5和Kv2.1 mRNA的表达.结果 左肺动脉结扎组2周及5周后大鼠右心室收缩压、平均压、右心室肥厚指数均较正常对照组和假手术组明显升高（均P＜0.05）.2周和5周后结扎组PAMT和WA/TA值均较正常对照组和假手术组显著增高（均P＜0.05）,即远端肺小动脉平滑肌层较其他两组明显增厚,管腔狭窄,肺血管重塑.肺动脉结扎可降低远端肺动脉平滑肌Kv1.5和Kv2.1 mRNA的相对表达量,结扎后2周及5周大鼠肺动脉平滑肌Kv1.5 mRNA相对表达量为（67.56±12.23）％和（55.98±6.84）％,Kv2.1 mRNA相对表达量为（59.71±6.25）％和（49.07±3.51）％,均低于同时间正常对照组和假手术组（均P＜0.05）.结论 用左肺动脉结扎法成功建立慢性栓塞性肺动脉高压大鼠模型,左肺动脉结扎可能通过下调大鼠肺动脉平滑肌电压依赖性钾通道Kv1.5、Kv2.1 mRNA的表达参与慢性栓塞性肺动脉高压的发生发展.Objective To establish the rat model of chronic thromboembolic pulmonary hypertension （CTEPH）,and to investigate the effect of pulmonary artery ligation on voltage-dependent potassium channel protein Kv1.5 and Kv2.1 mRNA expressions in rat pulmonary artery smooth muscle,further to clarify the mechanism of the CTEPH occurrence and development.Methods CTEPH rat models were established by left pulmonary artery ligation （LPAL） in male SD rats,and randomly divided into 2-week normal control group,2-week LPAL group,2-week sham operation group,5-week normal control group,5-week LPAL group and 5-week sham operation group（n=5 each）.Direct right heart manometry was used to determine the right ventricular systolic pressure （RVSP） and mean pulmonary arterial pressure （mPAP） in the 6 groups.The heart weight was measured to examine right ventricular hypertrophy index.HE staining was used to determine the changes of lung tissues and pulmonary vascular structures by measuring relative pulmonary artery medial thickness （PAMT）,and vessel wall area/total area （WA/TA）.Real-time quantitative PCR was used to determine the Kv 1.5 and Kv2.1 mRNA expressions in pulmonary artery smooth muscle.Results The RVSP,mPAP and right ventricular hypertrophy index in LPAL groups at 2 and 5 weeks were significantly increased compared with those in the normal control groups and sham operation groups （all P〈0.05）.The PAMT and WA/TA value in LPAL groups at 2 and 5 weeks were significantly increased compared with those in the normal control groups and sham operation groups （all P〈0.05）.Compared with the normal control groups and sham operation groups,significantly thicker distal pulmonary artery smooth muscle layer,vascular stenosis and pulmonary vascular remodeling were found in the LPAL groups at 2 and 5 weeks.Pulmonary artery ligation can reduce the relative expressions of Kv1.5 and Kv2.1 mRNA in distal pulmonary artery smooth muscle.At 2 and 5 weeks after ligation,the relative expressions of Kv1.5 and Kv2.1 mRN

关 键 词：高血压 肺性 肺栓塞 钾通道 电压门控 肺动脉平滑肌 

分 类 号：R544.1[医药卫生—心血管疾病]