迷走神经电刺激对野百合碱诱导的大鼠肺动脉高压的影响研究  

Effects of vagal nerve electrical stimulation on monocrotaline-induced pulmonary hypertension in rats

作　　者：张峰 钟冬祥 金旗 詹智 林大卫 管丽华 龚辉 葛均波 周达新 Zhang Feng;Zhong Dongxiang;Jin Qi;Zhan Zhi;Lin Dawei;Guan Lihua;Gong Hui;Ge Junbo;Zhou Daxin(Department of Cardiology,Zhongshan Hospital,Fudan University/Institute of Cardiovascular Diseases of Shanghai City/National Clinical Research Center for Radiology and Therapy,Shanghai,200032,P.R.China;Department of Cardiology,Jinshan Hospital,Fudan University,Shanghai,201508,P.R.China)

机构地区：[1]复旦大学附属中山医院心内科,上海市心血管病研究所,国家放射与治疗临床医学研究中心,上海200032 [2]复旦大学附属金山医院心内科,上海201580

出　　处：《老年医学与保健》2023年第1期122-127,138,共7页Geriatrics & Health Care

基　　金：上海市放射与治疗(介入治疗)临床医学研究中心基金(19MC1910300);复旦大学附属金山医院青年科研基金(JYQN-JC-202010)。

摘　　要：目的探索在野百合碱(monocrotaline,MCT)诱导的肺动脉高压大鼠模型中,给予迷走神经电刺激对肺动脉高压大鼠肺动脉压力和右心室功能的影响。方法将24只健康雄性SD大鼠随机分为3组:对照组、MCT组、迷走神经电刺激(vagus nerve stimulation,VNS)组,每组8只。MCT组和VNS组均行VNS刺激仪植入,MCT组及VNS组在植入1周后,分别按体质量注射MCT,对照组注射等量生理盐水,VNS组注射野百合碱后1周开启迷走神经刺激仪直至实验结束。3组大鼠均在基线、2周、3周行血压、心率监测,并在基线、3周行心脏超声评估心脏各指标。动物超声测得三尖瓣环收缩期位移及左室射血分数和右室面积变化分数。造模3周后,测量肺动脉收缩压及右室肥厚指数,免疫组化观察肺中小动脉增厚程度,酶联免疫吸附实验(enzyme linked immunosorbent assay,ELISA)检测大鼠血清中环磷酸鸟苷、一氧化氮、白细胞介素-6、白细胞介素-1β、去甲肾上腺素、血管紧张素Ⅱ的表达水平。结果MCT注射3周后,与对照组相比,MCT组及VNS组大鼠平均肺动脉压均显著升高(P<0.01),提示肺动脉高压大鼠造模成功;与MCT组相比,VNS组的平均肺动脉压、右心肥厚指数、肺中小动脉中膜厚度百分比显著下降(P<0.01),肺动脉加速时间、肺动脉主干内径、右室收缩末内径、右室舒张末内径、右室面积变化分数显著降低;ELISA检测提示VNS组较MCT组交感神经活性、肾素-血管紧张素-醛固酮系统水平及局部炎症水平显著降低(P<0.01)。结论迷走神经刺激可能通过降低交感神经活性从而改善大鼠肺中小动脉重构、肺动脉压力和右心功能。Objective To explore the effects of vagal nerve electrical stimulation(VNS)on pulmonary artery pressure and right ventricular function in rats with pulmonary hypertension(PH)induced by monocrotaline(MCT).Methods 24 healthy male SD rats were randomly divided into three groups:control group(n=8),MCT group(n=8)and VNS group(n=8).Both MCT group and VNS group were implanted with VNS stimulator.One week after implantation,MCT group and VNS group were injected with MCT according to body weight,while the control group was injected with the same amount of normal saline.In the VNS group,the vagus nerve stimulator was turned on one week after the injection of MCT until the end of the experiment.Blood pressure and heart rate were monitored at baseline,2 weeks and 3 weeks in all three groups,and echocardiography was performed at baseline and 3 weeks to evaluate cardiac parameters.The systolic displacement of tricuspid annulus,left ventricular ejection fraction and right ventricular area change fraction were measured by ultrasonic apparatus for small animals.After 3 weeks of modeling,pulmonary artery systolic pressure and right ventricular hypertrophy index were measured,the degree of pulmonary artery thickening was determined by immunohistochemistry,and the expression levels of cyclic guanosine monophosphate,nitric oxide,interleukin-6,interleukin-1β,norepinephrine and angiotensinⅡin serum were detected by enzyme-linked immunosorbent assay(ELISA).Results After 3 weeks of MCT injection,the mean pulmonary artery pressure of the MCT group and VNS group was significantly higher than that of the control group(P<0.01),suggesting the successful modeling of PH rats.Compared with the MCT group,the mean pulmonary artery pressure,right ventricular hypertrophy index,and percentage of pulmonary medium and small artery media thickness of the VNS group decreased significantly(P<0.01),and the pulmonary artery acceleration time,pulmonary artery main diameter,right ventricular end-systolic diameter,right ventricular end-diastolic diameter,an

关 键 词：肺动脉高压 迷走神经电刺激 交感神经系统 肾素-血管紧张素-醛固酮系统 

分 类 号：R544.1[医药卫生—心血管疾病]