实验性糖尿病心肌病大鼠模型建立及心脏功能和结构相关性分析

目的建立实验性糖尿病心肌病大鼠模型,观察心功能和结构变化,初步分析心脏功能和结构指标相关性。方法雄性Wistar大鼠随机分为正常对照组、高糖高脂膳食组和糖尿病心肌病模型组,采用高糖高脂膳食12周负荷一次性小剂量STZ腹腔注射建立糖尿病心肌病模型,观察各组动物心脏功能、心脏重量和心重指数、左心室形态和胶原含量等的变化。结果 (1)与正常对照组比较,糖尿病心肌病模型组大鼠左心室舒张末压(LVEDP)和最大舒张速率(-dp/dtmax)值显著升高(P0.05),心率(HR)、左心室收缩压(LVSP)、左心室最大收缩速率(+dp/dtmax)、每搏输出量(SV)和心排量(CO)明显降低(P0.05);全心重指数(HW/BW)和左心室重量指数(LVW/BW)明显升高(P0.01);常规HE染色显示心肌细胞排列紊乱,心肌细胞肥大,细胞核边缘不清等,室间隔和左心室壁厚度明显增加(P0.001,P0.05);心肌胶原含量明显增加(P0.05)。(2)大鼠心脏功能参数±dp/dtmax和CO值分别与结构参数HW/BW和LVW/BW呈现明显的相关性(P0.01或P0.05)。结论大鼠高糖高脂膳食喂养负荷小剂量STZ一次性腹腔注射,可造成心脏舒张和收缩功能紊乱以及心肌结构重塑,心脏功能与结构变化呈显著相关性,可复制实验性糖尿病心肌病模型。

Establishment of a Rat Model of Experimental Diabetic Cardiomyopathy and Correlations between Cardiac Functional and Structural Parameters

Objective The aim of this study was to establish a rat model of experimental diabetic cardiomyopathy,to observe the changes of cardiac function and structure,and to analyze the correlation between them.Methods Forty-five male Wistar rats（180 g-200 g） were randomly divided into 3 groups：the control group,high fat-high sucrose group（HSF） and diabetic cardiomyopathy model group（DC）.The rats in the control group were fed with normal food,rats in HSF and DC groups were fed with high fat-high sucrose diet（consisted of 20% sucrose,10% lard,2.5% cholesterol,1% bile salt and 66.5% normal food） for totally 12 weeks.Rats in the DC group were injected i.p.with a single dose of 30 mg /kg streptozotocin（dissolved in citric acid-sodium citrate buffer,pH = 4.5） after 6 weeks’feeding.FBG were tested after 72 hours and FBG ≥7.77 mmol /L was considered as the standard for establishment of diabetes mellitus.Rats in the control and HSF groups were i.p.injected with citric acid-sodium citrate buffer（pH = 4.5）.At the end of experiment（the twelfth week）,heart rate（HR）,stroke volume（SV）,cardiac output（CO）,left ventricular systolic pressure（LVSP）,left ventricular end diastolic pressure（LVEDP）,the maximum rate of myocardial contraction（＋ dp /dtmax） and the maximum diastolic rate of myocardium（-dp /dtmax） were measured using MP150 polygraph physiological signal recorder to evaluate the cardiac function.The whole heart weight（HW）,left ventricular weight（LVW）,HW /body weight（HW /BW）,LVW /BW,Interventricular septal thickness（IST）,left ventricular wall thickness（LVWT） and left ventricular collagen concentration were measured to assess the cardiac structure.Results Compared with the control group,rats in the DC group showed significant increase of LVEDP and-dp /dtmax（P 0.05） and decrease of LVSP,＋ dp /dtmax,HR,SV and CO（P 0.05）.It also exhibited significant increase of HW /BW and LVW /BW indexes（P 0.01）,IST and LVWT parameters（P 0.001,P 0.05） and collagen concentration（P 0.05）.Significant correlations between cardiac functional and structural parameters were also observed.Conclusions An experimental diabetic cardiomyopathy model in rats can be established by high fat-high sucrose diet with i.p.injection of streptozotocin,presenting similar clinical manifestation of diabetic cardiomyopathy in humans,and it shows remarkable correlation between the cardiac dysfunction and structural alterations.