大鼠糖尿病性心肌病的超声心动图研究

目的 应用超声心动图多普勒组织成像(DTI)及背向散射积分(IBS)技术评价糖尿病性心肌病大鼠左心室功能及心肌纤维化.方法 通过腹腔注射链尿左菌素(65 mg/kg)建立SD大鼠糖尿病模型,模型成功后第4、12、24周,测定左室缩短分数(LVFS)、二尖瓣121舒张早期与舒张晚期血流速度比值(E/A)、二尖瓣环DTI舒张早期与舒张晚期峰值运动速度比值(Ea/Aa)以及左室后壁心肌校正IBS(IB%)、IBS周期变异幅度(CVIB).Masson染色观察胶原在心肌间质的沉积.同期检测心脏质量指数(HWI)、心肌SERCA2a活性及CTGF在心肌的分布及表达.并与同龄正常大鼠组进行比较.结果 ①糖尿病组舒张功能减低最早出现在模型成功后第4周(E/A<1),并逐渐加重,24周达二尖瓣血流假性正常阶段(E/A>1),DTI可帮助鉴别(Ea/Aa<1).与对照组相比,糖尿病大鼠IB%明显增高(P<0.05),CVIB于第24周时明显减低,差异均有统计学意义(P<0.05).LVFS无明显变化.②与对照组相比,糖尿病大鼠HWI、心肌胶原容积分数、血管周围胶原面积及结缔组织生长因子表达均明显增高,差异均有统计学意义(P<0.05),且与IB%呈正相关,同时SERCA2a活性明显减低,差异有统计学意义(P<0.05).结论 超声心动图能早期检测到左室功能异常和心肌纤维化.在二尖瓣血流假性正常阶段,DTI可协助诊断.糖尿病心肌病可能与SERCA2a活性下降及CTGF的过表达有关.

The echoeardiographic study on diabetic cardiomyopathy of rats

Objective To valuate the left ventricular function and myocardial fibrosis using Dopple tissue imaging(DTI) and integrated backscatter(IBS) in diabetic cardiomyopathy(DCM) rats. Methods Diabetes mellitus(DM) in healthy male SD rats was induced by single injection of streptozotocin (STZ,Sigma) into intraperitoneal at a dose of 65mg/kg body weight. Left ventricular fractional shortening (LVFS),ratio of peak early to late diastolic mitral inflow velocity(E/A) by color Doppler flow imaging-pulsed wave (CDFI-PW), ratio of peak early to late diastolic mitral annulus velocity (Ea/Aa) by DTI,myocardial calibrated IBS (IB%), cyclic variation of IBS(CVIB) by IBS, were determined in rats of 4,12 and 24 weeks after DM was induced. Heart weight index(HWI), Masson's trichrome staining, expression of connective tissue growth factor(CTGF) and activity of sarcoplasmic reticulum Ca2+ -ATPase(SERCA2a) in heart were measured, while the age-matched health rats served as control group. Results ① Diastolic dysfunction of left ventricular was found in diabetic rats detected by CDFI-PW(E/A<1) at the 4th week,and developed gradually. Pseudonormal filling(E/A>1) was found in major diabetic rats at the 24th week,which could be identified by DTI(Ea/Aa<1). The IB% of left ventricular posterior wall was significantly higher in diabetic rats than those in the control group( P<0.05), but the CVIB of the 24th week diabetic rats was lower(P<0.05). The LVFS had no great alteration in six groups(P>0.05).②Compared with the control group, the activity of SERCA2a was reduced, while HWI, collagen volume fraction(CVF),perivascular collagen area(PVCA) and the expression of connective tissue growth factor(CTGF) protein in heart were increased in diabetic rats (P<0.05), and correlation between IB% and HWI, CVF, PVCA,CTGF was significant (P<0.05). Conclusions DTI and IBS can assess early left ventrieular diastolic function and fibrosis of diabetic cardiomypathy in STZ-induced diabetic rats. DTI echoeardiography can identify "pseudonormal" mitral inflow patterns. DCM may be relatived with overexpression of CTGF and decreasion of SERCA2a activity.