培哚普利联合螺内酯对肾性高血压大鼠心肌纤维化及转化生长因子-β_1的影响

Effects of perindopril and spironolactone combination on myocardial fibrosis and expression of transforming growth factor-β1 in renovascular hypertensive rats

目的探讨培哚普利和螺内酯对肾性高血压大鼠心肌纤维化及转化生长因子-β1表达的影响。方法建立双肾一夹肾血管性高血压大鼠模型,将32只实验大鼠随机分为4组(n=8):假手术组、高血压组、培哚普利组,培哚普利+螺内酯组(联合组),术后4周末开始灌胃培哚普利组给予培哚普利2mg·kg-1·d-1,联合组给予培哚普利2mg·kg-1·d-1+螺内酯20mg·kg-1·d-1,共8周。测量大鼠尾动脉收缩压(SBP)、心肌羟脯氨酸浓度(HC)、心肌胶原容积分数(CVF)、血管周围胶原容积分数(PVCA)及转化生长因子-β1(TGF-β1)的表达。结果和高血压组相比,假手术组、联合组及培哚普利组SBP、HC、CVF、PVCA以及TGF-β1的表达显著降低(P<0.01);和培哚普利组相比,联合组HC、CVF、PVCA及TGF-β1的表达明显降低(P<0.05)。结论培哚普利和两药联合都可通过降低TGF-β1的表达来抑制RH大鼠心肌纤维化的进展,且联合应用优于单独应用。

Objective To investigate the effects of perindopril in combination with spironolactone on myocardial fibrosis and expression of transforming growth factor-β1 （TGF-β1） in renovascular hypertensive （RH） rats. Methods RH models were constructed using the two--kidney-one-clip （2K1C） technique in 32 rats, which were randomized into the sham group, RH group, perindopril group and perindopril ＋ spironolactone group （combination group）. After four weeks, rats in the perindopril group received perindopril 2 mg·kg^-1·d^-1while the combination group received perindopril 2 mg·kg^-1·d^-1 and additional spironolactone 20 mg·kg^-1·d^-1 for eight weeks. Data on caudal systolic blood pressure （SBP）, concentration of cardiac hydroproline （HC）, collagen volume fraction （CVF）, perivascular collagen area （PVCA） and expression of transforming growth factor-β1（TGF-β1） in left ventricular tissue were evaluated. Results Compared with the RH group, SBP, HC, CVF, PVCA and expression of TGF-β1 decreased remarkably in the sham group, perindopril group and combination group （P〈0. 01）; compared with perindopril group, HC, CVF, PVCA and expression of TGF-β1 decreased in combination group （P〈0.05）. Conclusion Perindopril alone or in combination with spironolactone may reverse development of myocardial fibrosis by down-regulating the expression of TGF-β1 in renovascular hypertensive rats. Combination treatment was shown to result in better effect on myocardial fibrosis and expression of TGF-β1 than perindopril alone.