非诺贝特对慢性心力衰竭大鼠心室重构的影响

目的研究非诺贝特对慢性心力衰竭大鼠心室重构的影响。方法 68只8周龄健康♂Wistar大鼠随机分为假手术组(Sh组,18只)和模型组(M组,50只),模型制备采用腹主动脉缩窄术,8周后将成功存活的38只模型组大鼠随机分为非诺贝特组(F组,18只)和对照组(C组,20只),分别给予非诺贝特150 mg.kg-1或生理盐水灌胃,每天1次,共10周。结果①干预前后,与Sh组比较,C组及F组LVEF、FS%、±dp/dtmax均降低(P<0.05),LVEDd、LVEDs、LVSP、LVEDP均升高(P<0.05);C组与F组间差异无统计学意义(P>0.05)。②干预后,C组、F组心肌LVW/BW、CVF指标较Sh组增高(P<0.05);F组LVW/BW较C组增高、CVF指标较C组明显降低(P<0.05)。③干预后,与Sh组比较,C组和F组心肌ET-1 mRNA明显增高(P<0.05);与C组比较,F组明显降低(P<0.05)。④干预后,与Sh组比较,F组和C组心肌eNOS蛋白水平明显降低(P<0.05);与C组比较,F组明显升高(P<0.05)。结论非诺贝特下调慢性心力衰竭大鼠心肌ET-1基因表达,上调eNOS的表达,抑制心肌间质纤维化,改善心室重构;但对心脏功能无影响。

Effect of fenofibrate on left ventricle remodeling in rats with chronic heart failure after aorta constriction

Aim To investigate the effects of fenofibrate on left ventricle remodeling in in rats with chronic heart failure after aorta constriction.Methods Sixty-five 8-week-old male wistar rats were randomized to two groups: Sham group(n=15) and Model group(n=50).An abdominal aorta constricted(AAC) model of pressure-overloaded heart was created in M group.After the surgery for 8 weeks,thirty-eight living rats in M group were randomly assigned to the following subgroups: group F(n=18) or group C(control group,n=20).Fenofibrate(fenofibrate 150 mg·kg-1·d-1) or equivalent physiological saline was administered to the rats in group F and control group respectively for 10 weeks.Results Eight weeks postoperatively,the LVEF,FS%,±dp/dtmax were decreased(P<0.05),and the LVEDd,LVEDs,LVSP,LVEDP were increased in group F or group C compared with those in Sham group(P<0.05).These parameters were not significantly different between group F and group C(P<0.05).At the end of study,the LVW/BW and CVF in group C and group F were significantly increased compared with those in Sham group(P<0.05).Compared with group C,the LVW/BW was increased and the CVF was decreased in group F(P<0.05).The level of ET-1 mRNA in left ventricle in group C and group F was higher than that in group Sham(P<0.05),but it was lower in group F than in group C(P<0.05).The expression of eNOS in left ventricle was decreased in group F and group C,but group F showed a higher level of eNOS than group C(P<0.05).Conclusions Fenofibrate has a potential effect on inhibiting the progression of the myocardial fibrosis in rats with chronic heart failure due to pressure overloaded,but it has no effect on improving cardiac function.The mechanism that fenofibrate prevents the progression of chronic heart failure is probably through either inhibiting the expression of ET-1 mRNA or upregulating the level of eNOS in myocardium.