标题:
Evaluating Cardioprotective Effects of sEH Gene Deletion Using Pulse Wave Doppler and EKV Echocardiography
讲者:
谭伟江
单位:
广东省实验动物监测所
播放:
2853
论文摘要:
Objective: The benefical effects of arachidonic acid metabolism pathway is terminated at the point of soluble epoxide hydrolase (sEH) hydrolyzing EETs into downstream molecules. Our previous results revealed that deficiency or inhibition of sEH resulted in significantly improvement in systolic and diastolic function, mitochondrial respiration, ATP contents and mitochondrial enzymatic activities in hearts. Here we further using pulse wave Dopple and EKV echocardiography to identify various aspects of cardioprotective effects of sEH inhibition.
Methods: 20 of WT and 20 of sEH knock-out mice were used in this experiment, each genotype were randomly divide into Sham (n=10) or MI group (n=10). Myocardial infarction (MI) was established by ligating the left anterior descending coronary artery (n = 15), and in Sham group, mice underwent open chest surgery without artery ligation. Cardiac morphological structure, diastolic function, systolic blood pressure and ventricular wall motion of all mice were accessed by regular M-model and pulse wave Doppler echocardiography 3 days pre- and 7 days post-surgery. A EKV imaging method was used to access wall motion, and a AHA(The American Heart Association)score system was adapted to determine the degrees of abnormal movement post-MI. Briefly in this score system, the normal motion is calculated as “1”, and the higher numbers of the wall movement indicates more impairments in function. After echocardiography, mouse heartswerecollected for HE staining and infarction area analysis.
Results: 1)Consistent with our published echocardiography data,sEH deletion stopped the MI-induced ventricular enlargement and wall remodeling. 2) Results from pulsed wave Doppler recording at the mitral valves showed that isometric diastolic time was 15.01±0.41 ms in sEH deleted MI mice, while 18.53±1.45 ms in WT MI mice,indicated sEH deletion is able to restore the Post MI relaxation function of the heart.Recording at thevalves of pulmonary vein also showed that she deletion increased the peak ofdiastolic wave(d wave) from 430.98 ±68.85 mm/s to 620.01 ±44.63 mm/s post MI, close to the values in the WT sham groups.3) The local wall motion determined by the EKV analysis indicated that MI induceabnormal movement frequently(3.04±0.13 vs. 1.10±0.04 of the scores), but sEH deletion successfully reduced the remodeling, as seen the scores were close to the normal value (1.58 ±0.06 of the scores). 4)Histology examination showed that MI surgery induced infarction, but sEH deletion fully stopped these impairments.
Conclusion: MI hearts are protected by sEH deletion in restoring relaxation function, reducing abnormal movement and inhibiting myocardial infarction.