药物联合治疗对改善肾血管性高血压大鼠左室重构的对比研究

Comparison of combined medications on improving left ventricular remodeling in Goldblatt rats

目的通过贝那普利分别和比索洛尔、替米沙坦、氨氯地平联合应用治疗肾血管性高血压大鼠,观察并对比各组药物联合治疗的降压效果,并探讨其对左室重构的作用。方法两肾一夹法建立高血压大鼠模型,54只SD大鼠随机分为:假手术组(A组,n=10);高血压组(B组,n=11);β受体阻滞剂+血管紧张素转换酶抑制剂(ACEI)组(C组,n=11)予以比索洛尔5 mg/(kg.d)及贝那普利5 mg/(kg.d)灌胃;ACEI+血管紧张素Ⅱ受体拮抗剂(ARB)组(D组,n=11)予以贝那普利5 mg/(kg.d)及替米沙坦10 mg/(kg.d)灌胃;ACEI+钙通道拮抗剂组(E组,n=11)予以贝那普利5 mg/(kg.d)及氨氯地平2.5 mg/(kg.d)灌胃;饲养20周,期间每2周给大鼠测量鼠尾动脉压和超声心动图;20周后采集标本,用免疫组化法检测胶原Ⅲ、胶原Ⅳ及心钠素(ANF)。结果各用药组降压明显,其中E组与A组血压相近,且比其他用药组血压降低更明显(P<0.05)。与A组比较,C组LVMI明显上升(P<0.05);D组和E组无显著变化,但B组收缩末期左室内径(LVESD)和舒张末期左室内径(LVEDD)明显扩大,与A组相比具有统计学差异(P<0.05);且B组舒张末期左室后壁厚度(LVPWD)和收缩末期左室后壁厚度(LVPWS)明显变薄(P<0.05),相对室壁厚度(RWT)明显下降(P<0.05);C组LVPWD、LVPWS和RWT明显提高,与A组相比具有统计学差异(P<0.05)。C组胶原Ⅲ、胶原Ⅳ含量较B组降低(P<0.05),D组和E组亦显著降低(P<0.01);与A组比较,B组胶原Ⅲ、胶原Ⅳ和ANF明显升高(P<0.05);与B组比较,各药物治疗组ANF显著降低(P<0.01)。结论在降压和靶器官保护方面,贝那普利和氨氯地平联用疗效最好。

Objective To compare the efficacy of combined medications on left ventricular remodeling in Goldblatt rats （ two kidney one clip hypertensive rats ）. Methods Fifty-four Goldblatt rats of 5- 6 weeks old were randomly divided into 5 groups ： sham group （ group A, n = 10 ） ; hypertension group （ group B, n = 11 ） ; 13 adrenergic receptor blocker （β-B） ＋ angiotensin converting enzyme inhibitor（ACEI） group [ group C, bisoprotol 5 mg/（ kg · d） ＋ benazepril 5 mg/ （ kg · d）, n = 11 ] ; ACEI ＋ angiotensin Ⅱ type Ⅰ receptor blocker （ARB） group [ group D, benazepril 5 mg/（ kg · d） ＋ telmisartan 10 mg/（ kg · d） ,n = 11 ] , ACEI ＋ calcium channel blocker（CCB） group [ group E, benazepril 5 mg/（ kg · d） ＋ amlodipine 10 mg/（ kg · d） ,n = 11 ] ; Being fed for 20 weeks along with blood presure monitored and echocardiography performed every two weeks, the rats were sacrificed, the blood and hearts were collected, and the concentration of collagen Ⅲ, collagenlVand ANF were detected by immunohistochemistry. Results The blood pressure of rats in each medication group was reduced significantly. The blood pressure of rats was reduced more significantly in group E （P 〈 0.01 ） , whose result is close to that of group A, and lower than that in other medication group. Compared to group A, the cardiac geometries of group B and group C were changed. RWT was raised more significantly in group C than that in group A, and reduced more significantly in group B than that in group A. RWT in group D and group E was close to that in group A. The concentration of collagen Ⅲ, collagen Ⅳ and ANF in medication groups were significantly lower than those in group B. Conclusions Benazepril combined with amlodipine is effective in lowering blood pressure and protecting target organ.