一种新的射血分数保留型心力衰竭大鼠模型构建方法  

A novel method for heart failure with preserved ejection fraction rat model

作　　者：李依璘 杨洁 李国旗 张新宇 李玉琳[1] LI Yilin;YANG Jie;LI Guoqi;ZHANG Xinyu;LI Yulin(Department of Vascular Biology,Beijing Anzhen Hospital,Capital Medical University,Beijing Institute of Heart,Lung and Blood Vessel Diseases,Beijing 100029,China)

机构地区：[1]首都医科大学附属北京安贞医院-北京市心肺血管疾病研究所、教育部心血管重塑相关疾病重点实验室-心血管重大疾病防治协同创新中心,100029

出　　处：《心肺血管病杂志》2024年第7期781-788,共8页Journal of Cardiovascular and Pulmonary Diseases

基　　金：国家自然科学基金(82230013,82100397)。

摘　　要：目的:优化射血分数保留型心力衰竭(heart failure with preserved ejection fraction,HFpEF)大鼠模型构建方法,为研究HFpEF提供实验模型。方法:10周龄,Zucker糖尿病脂肪/自发性高血压心力衰竭肥胖(obese zucker diabetic fatty/spontaneously hypertensive heart failure F1 hybrid,ZSF1-obese)大鼠和ZSF1瘦型(ZSF1-lean)大鼠分为三组,分别为实验组[(ZSF1-obese大鼠,饮水中给予一氧化氮合酶抑制剂(inhibition of constitutive nitric oxide synthase,L-NAME),n=6]、经典模型组(ZSF1-obese大鼠,普通水,n=3)、空白对照组(ZSF1-lean大鼠,普通水,n=4)。三组均以普通饲料饲养。实验组给药10周后采集三组的血压、葡萄糖耐量、心脏超声、心脏磁共振成像、生化指标数据。结果:实验组在给药10周后收缩压和舒张压分别达到(155.0±6.6)mmHg(1mmHg=0.133kPa)和(119.4±10.9)mmHg,比起经典模型组明显升高(分别为P=0.0001和P=0.0143),达到高血压标准,而经典模型组和对照组均没有达到高血压标准。心脏超声结果显示三者均呈现射血分数保留(均P>0.05),实验组和经典模型组有相似的舒张功能障碍、心肌肥厚和糖耐量受损(P>0.05)。生化指标也显示实验组和经典模型组存在相似的脂肪肝、肾功能减退。结论:与传统的ZSF1大鼠直接作为HFpEF模型相比,联合L-NAME的ZSF1大鼠作为HFpEF模型能更全面呈现HFpEF的疾病特征,包括高血压,舒张功能障碍、糖耐量受损等表型。Objective:To optimize the construction method of the rat model of heart failure with preserved ejection fraction(HFpEF)and provide an optimized experimental model for HFpEF.Methods:10-week-old Zucker diabetic fatty/Spontaneously hypertensive heart failure F1 hybrid(ZSF1)-obese and ZSF1-lean rats were divided into three groups:the experimental group(ZSF1-obese rats given inhibition of constitutive nitric oxide synthase(L-NAME)in drinking water,n=6),the classical model group(ZSF1-obese rats given ordinary water,n=3),and blank control group(ZSF1-lean rats given ordinary water,n=4).All three groups were fed a chow diet.After 10 weeks of administration,parameters including blood pressure,glucose tolerance,echocardiography,cardiac magnetic resonance imaging,and biochemical parameters were assessed among all three groups.Results:Following 10-week administration,the experimental group exhibited significantly elevated systolic blood pressure(155.0±6.6)mmHg and diastolic blood pressure(119.4±10.9)mmHg compared to the classical model group(P=0.0001 and P=0.0143,respectively),meeting the criteria for hypertension.In contrast,neither the classical model group nor the control group met the criteria for hypertension.Echocardiography showed preserved ejection fraction in all three groups(all P>0.05).The experimental and classical model groups exhibited similar diastolic dysfunction,cardiac hypertrophy,and impaired glucose tolerance(P>0.05).Biochemical parameters indicated comparable fatty liver and renal dysfunction in the experimental and classical model groups.Conclusions:Utilizing ZSF1-obese rats with L-NAME for HFpEF modeling,as opposed to traditional ZSF1-obese rats,better captures HFpEF characteristics,including hypertension,diastolic dysfunction,and impaired glucose tolerance.

关 键 词：射血分数保留型心力衰竭 大鼠模型 高血压 Zucker糖尿病脂肪/自发性高血压心力衰竭大鼠 

分 类 号：R54[医药卫生—心血管疾病]