Erokhina I L, Okovityĭ S V, Kulikov A N, Kazachenko A A, Emel'ianova O I
Tsitologiia. 2009;51(9):735-40.
Activation of the renin-angiotensin system (RAS) plays a critical role in the pathogenesis of heart failure (HF). We studied the effect of lisinopril (LP) and fosinopril (FP), the inhibitors of angiotensin-converting enzyme, and of losartan (LT), the antagonist of Angiotensin II receptors, on the behavior of multifunctional mast cells (MCs) under experimental HF. The inhibitors of RAS were daily injected during 4 weeks in 4 weeks after two (at 24-h interval) isoproterenol injections. MCs of different degrees of maturity were identified on paraffin sections stained with Alcian blue and Safranin. Expressiveness of HF was estimated by functional parameters with the help of echocardiogram and by morphological markers. The MC density in the myocardium of the intact rats as well as of the rats with HF, both treated and untreated with the preparations, was relatively low: from 3 to 4 cells/mm2. The MC density in the pericardium of the intact rats was several times higher than in the myocardium: 35 +/- 7 cells/mm2. The density ofpericardial MC under HF was 1.7 higher than that in the intact rats at the expense of the increase in the density of Alcian-positive immature cells (P < 0.05). The injections of LP increased the MC density still in 1.4 times at the expense of the density of Safranin-positive mature cells (P < 0.01). The injections of FP and LT had no influence on the MC density and the balance of cells of different degrees of maturity in the pericardium. 96-99% of MCs in lung were Alcian-positive cells. The density of such cells in the intact rats, in the rats with HF, and in the rats with HF treated with FP was 30 cells/mm2. The injections of LP and LT decreased the density of pulmonary MCs up to 7 cells/mm2 (P < 0.01) and 19 cells/mm2 (P < 0.05), respectively. Functional parameters of the hearts were consistent with the data of morphological analyses. Myocardium function improvement was noted only in the rats with HF treated with FP and LT. The reaction of MCs (as cell elements of "tissue" RAS) to injections of inhibitors of RAS was various in the myocardium, pericardium and lung of the rats with HF. The injections of LP stimulated maturation of the resident MCs in the pericardium and the replenishment of the population through immature cells migrating from the outside. It allows us to suppose an intensification of secretory activity of the cells. In contrast, the injections of LP and LT reduced the pulmonary MC population.
肾素-血管紧张素系统（RAS）的激活在心力衰竭（HF）的发病机制中起关键作用。我们研究了血管紧张素转换酶抑制剂赖诺普利（LP）和福辛普利（FP）以及血管紧张素II受体拮抗剂氯沙坦（LT）对实验性HF下多功能肥大细胞（MCs）行为的影响。在两次（间隔24小时）注射异丙肾上腺素后的4周内，连续4周每日注射RAS抑制剂。在经阿尔辛蓝和番红染色的石蜡切片上鉴定不同成熟度的MCs。借助超声心动图的功能参数和形态学标记物评估HF的严重程度。完整大鼠以及用制剂治疗和未治疗的HF大鼠心肌中的MC密度相对较低：每平方毫米3至4个细胞。完整大鼠心包中的MC密度比心肌中的高几倍：每平方毫米35±7个细胞。HF下心包MC的密度比完整大鼠高1.7倍，这是以阿尔辛阳性未成熟细胞密度增加为代价的（P<0.05）。注射LP使MC密度增加了1.4倍，这是以番红阳性成熟细胞密度增加为代价的（P<0.01）。注射FP和LT对心包中MC密度以及不同成熟度细胞的平衡没有影响。肺中96-99%的MC是阿尔辛阳性细胞。完整大鼠、HF大鼠以及用FP治疗的HF大鼠中此类细胞的密度为每平方毫米30个细胞。注射LP和LT分别使肺MC密度降至每平方毫米7个细胞（P<0.01）和19个细胞（P<0.05）。心脏的功能参数与形态学分析数据一致。仅在用FP和LT治疗的HF大鼠中观察到心肌功能改善。HF大鼠心肌、心包和肺中MCs（作为“组织”RAS的细胞成分）对RAS抑制剂注射的反应各不相同。注射LP刺激心包中驻留MC的成熟，并通过从外部迁移的未成熟细胞补充细胞群体。这使我们推测细胞分泌活性增强。相反，注射LP和LT减少了肺MC群体。
