卡托普利、西地那非对右心衰竭幼鼠TGF-β1表达的影响

Effects of captopril and sildenafil citrate on TGF-β1 levels in juvenile rats with right heart failure

目的:了解野百合碱(MCT)致右心衰竭幼鼠中转化生长因子β1(TGF-β1)的变化以及卡托普利、西地那非对其的干预作用。方法:雄性SD大鼠78只随机分为对照组、模型组,模型组腹腔注射MCT诱发肺动脉高压致右心衰竭模型,对照组腹腔注射生理盐水。4周后对照组分为N1组和N2组,模型组随机分为F1组、F2组、卡托普利(C)组、西地那非(S)组和C+S组。N1组、F1组于4周末处死观察心肌病理学变化,同时C组、S组、C+S组开始给予相应药物灌胃,N2组和F2组予等量蒸馏水灌胃,均至6周,测每组存活大鼠相关生理指标。ELISA法检测各组血清TGF-β1水平,免疫组化方法检测右心室心肌组织中TGF-β1蛋白表达。结果:F2组血清TGF-β1水平和心肌组织中TGF-β1蛋白表达均较N2组高(t=10.088,7.259,P均<0.001)。C组、S组右室肥厚指数和心肌组织中TGF-β1蛋白表达均低于F2组(P<0.05);C和S的交互效应有统计学意义(F=6.630,7.183,14.905,P均<0.05)。F2组血清TGF-β1水平与心肌TGF-β1蛋白的表达呈正相关(r=0.665,P<0.001)。结论:卡托普利或西地那非对右心衰竭有一定的治疗作用,两者联用优于单用。

Aim：To examine transforming growth factor beta 1 （ TGF-β1 ） levels in right ventricular in juvenile rats with right heart failure （ RHF） and the intervention effects of captopril and sildenafil citrate on them .Methods：A total of 78 SD rats were randomized into two groups：RHF and control .Rats in the RHF group were injected monocrotaline for 4 weeks to induce RHF,then were randomly allocated into group F1,group F2,captopril（C） group,sildenafil citrate（S） group and group C＋S.Rats in the control group were injected with normal saline ,and randomly allocated into group N 1 and group N2 .The rats in the F1 and N1 groups were sacrificed for observing pathological changes in the myocardium .At the same time,group C,group S,group C＋S were separately given intragastric administration of captopril ,sildenafil citrate,captopril and sildenafil citrate for 2 weeks.Group F2 and N2 were given distilled water of equal dose for 2 weeks.Some physiological indexes were measured .Serum TGF-β1 levels were measured using ELISA .TGF-β1 protein expression was measured by immunhistochemistry .Results：Serum TGF-β1 levels and TGF-β1 protein were higher in group F 2 than those in group N 2 （t=10.088,7.259,P〈0.001）.Right ventricular hypertrophy index and TGF-β1 protein in group C and group S were low-er than those in group F2（P〈0.05）.There was significant interaction between captopril and sildenafil citrate （F=6.630, 7.183,14.905,P〈0.05）.There was a positive correlation between serum TGF-β1 levels and myocardial TGF-β1 protein expression in group F2 （r=0.665,P〈0.001）.Conclusion： Captopril and sildenafil citrate could have protection for RHF,and the combined use of the 2 drugs shows marked curative effect than single use any one of them .