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2026 年第 7 期 第 21 卷

模拟维持性血液透析心力衰竭机制大鼠模型的构建与评价

Establishment and evaluation of a rat model simulating the mechanism of heart failure in maintenance hemodialysis

作者:王彦斌1陈旭1邓宁2王息兰1梁瑞宁2张星平1

英文作者:Wang Yanbin1 Chen Xu1 Deng Ning2 Wang Xilan1 Liang Ruining2 Zhang Xingping1

单位:1新疆医科大学第四附属医院(第四临床医学院)肾内科,乌鲁木齐830099;2新疆医科大学,乌鲁木齐830000

英文单位:1Department of Nephrology The Fourth Hospital (The Fourth Clinical Medical College) of Xinjiang Medical University Urumqi 830099 China; 2Xinjiang Medical University Urumqi 830000 China

关键词:维持性血液透析;心力衰竭;大鼠模型

英文关键词:Maintenancehemodialysis;Heartfailure;Ratmodel

  • 摘要:
  • 目的 构建与评价模拟维持性血液透析(MHD)心力衰竭机制大鼠模型。方法 选取SD大鼠26只,采用随机数字表法将大鼠分为2组:对照组6只,食用油灌胃;造模组20只,腺嘌呤食用油溶液灌胃模拟尿毒症因素;阿霉素腹腔注射模拟心力衰竭和尿毒症因素;溴酸钾溶液代替饮水模拟微炎症因素。观察时间6周。观察指标包括各组大鼠精神状态、反应、体重、摄食量等一般情况、肾功能、C反应蛋白(CRP)、血压及心率,超声心动图相关指标[左心室射血分数(LVEF)、缩短分数、收缩末期室间隔厚度(IVSS)、左心室收缩末期后壁厚度(LVPWS)、左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、左心室舒张末期容积(LVEDV)、左心室收缩末期容积(LVESV)],心脏质量指数[全心质量指数(HM/BM)与左心室质量指数(LVM/BM)],透射电镜观察心肌病理。结果 造模组第6周末存活10只,死亡率50%。造模组体重自第1周末开始即显著低于对照组(均P<0.001),自第3周末开始呈轻微缓慢下降趋势;摄食量自第2周开始显著低于对照组(均P<0.001)。造模组血尿素氮、血肌酐自1周末开始即显著高于对照组,后续呈显著升高趋势,各时点均高于对照组(均P<0.001)。第6周末造模结束后造模组CRP显著高于对照组[(17.27±1.88)mg/L比(0.99±0.09)mg/L](P<0.01)。第6周末造模结束后造模组收缩压、舒张压、MAP及心率均显著低于对照组,LVEF、缩短分数、IVSS、LVPWS均显著低于对照组,LVEDD、LVESD、LVEDV、LVESV、HM/BM及LVM/BM均显著高于对照组(均P<0.001)。造模组电镜下病理损伤严重。结论 本研究所构建的模拟MHD心力衰竭机制大鼠模型按照尿毒症毒素、心力衰竭及微炎症大鼠造模标准评价均达标,能够真实、全程地模拟MHD心力衰竭临床和病理发展过程,与临床实际相似,可用于疾病的深入研究。

  • Objective To establish and evaluate a rat model simulating the mechanism of heart failure in maintenance hemodialysis (MHD). Methods A total of 26 SD rats were selected and divided into two groups by random number table method: 6 rats in the control group were given edible oil by gavage; 20 rats in the model group were treated with adenine edible oil solution by gavage to simulate uremic factors, intraperitoneal injection of doxorubicin to simulate heart failure and uremic factors, and potassium bromate solution instead of drinking water to simulate microinflammatory factors. The observation period lasted 6 weeks. General conditions including mental state, response, body weight and food intake, renal function, C-reactive protein (CRP), blood pressure and heart rate were observed. Echocardiographic parameters included left ventricular ejection fraction (LVEF), fractional shortening, interventricular septal end-systolic thickness (IVSS), left ventricular posterior wall end-systolic thickness (LVPWS), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV). Heart mass indexes included whole heart mass index (HM/BM) and left ventricular mass index (LVM/BM). Myocardial pathology was observed by transmission electron microscope. Results Ten rats in the model group survived at the end of the sixth week, with a mortality rate of 50%. The body weight of the model group was significantly lower than that of the control group starting from the end of the first week (all P<0.001) and decreased slightly and slowly since the third week. Food intake was significantly lower than that of the control group from the second week onward (all P<0.001). Serum urea nitrogen and creatinine in the model group were significantly higher than those in the control group starting from the first week and increased obviously at subsequent time points (all P<0.001). At the end of the sixth week, CRP level in the model group was significantly higher than that in the control group [(17.27±1.88)mg/L vs (0.99±0.09)mg/L](P<0.01). Meanwhile, systolic blood pressure, diastolic blood pressure, mean arterial pressure and heart rate in the model group were markedly lower than those in the control group; LVEF, fractional shortening, IVSS and LVPWS were significantly decreased; LVEDD, LVESD, LVEDV, LVESV, HM/BM and LVM/BM were significantly increased (all P<0.001). Severe myocardial pathological damage was observed under electron microscope in the model group. Conclusions The established rat model simulating MHD-related heart failure meets the evaluation criteria of uremic toxin, heart failure and microinflammation modeling. It can truly and completely simulate the clinical and pathological progression of MHD complicated with heart failure with good clinical similarity, and is suitable for in-depth experimental research of the disease.

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