Department of Medicine and Biology, Pedagogical University, Yaroslavl, Russia.
Clin Hemorheol Microcirc. 2011;48(4):231-40. doi: 10.3233/CH-2011-1415.
This study was designed to investigate whether the red cell aggregation depends on its initial level under drug therapy or cell incubation with bioactive chemical compounds. Sixty six subjects were enrolled onto this study, and sub-divided into two groups: the first group of patients (n = 36) with cerebral atherosclerosis received pentoxifylline therapy (400 mg, thrice daily) for 4 weeks. The patients of the second group were initially treated with Epoetin beta 10,000 units subcutaneously thrice a week, for 4 weeks. The second group - adult anemic patients (n = 30) with the confirmed diagnosis of solid cancer (Hb < 100 g/L). After 4 weeks of pentoxifylline treatment the red cell aggregation increased (p < 0.05) in the patients with initially low RBCA. On the other hand in the patients with initially high RBCA treatment with pentoxifylline reduced it markedly (p < 0.01). In vitro experiments with pentoxifylline RBC incubation resulted in a decrease of the initially high RBCA by 47% (p < 0.01), whereas in the sub-group with initially low RBCA it increased. It was observed that after 4 weeks of epoetin-beta treatment 75% the anemic patients with initially high RBCA had an aggregation lowering. The drop of aggregation was about 34% (p < 0.01). At the same time 25% of the study patients had a significant RBCA increase (p < 0.05) after treatment. The initially low red cell aggregation after incubation with epoetin-beta was markedly increased by 122% (p < 0.05). On the contrary initially high RBCA was reduced by 47% (p < 0.05). When forskolin (10 μM) was added to the RBC suspensions the RBCA was increased in sub-group of subjects with initially low aggregation and it was decreased in sub-group with initially high one. The similar RBCA changes were observed when RBC suspensions were incubated with vinpocetine, calcium ionophore (A23187), Phorbol 12-myristate 13-acetate (PMA) as a protein kinase C (PKC) stimulator. A major finding of this study is that the red cell aggregation effects of some drugs depend markedly on the initial, pre-treatment aggregation status of the patients. These results demonstrate that the different red blood cell aggregation responses to the biological stimuli depend strongly on the initial, pre-treatment status of the subject and the most probably it is connected with the crosstalk between the adenylyl cyclase signaling pathway and Ca2+ regulatory mechanism.
本研究旨在探讨红细胞聚集是否取决于药物治疗或细胞与生物活性化学化合物孵育时的初始水平。66 名受试者被纳入本研究，并分为两组：第一组患者（n=36）患有脑动脉粥样硬化，接受己酮可可碱治疗（400mg，每日三次）4 周。第二组患者最初接受皮下注射促红细胞生成素β 10000 单位，每周三次，共 4 周。第二组-成年贫血患者（n=30），经证实患有实体瘤（Hb<100g/L）。经过 4 周的己酮可可碱治疗，初始 RBCA 较低的患者红细胞聚集增加（p<0.05）。另一方面，初始 RBCA 较高的患者用己酮可可碱治疗后显著降低（p<0.01）。体外实验中，己酮可可碱孵育红细胞导致初始 RBCA 降低 47%（p<0.01），而在初始 RBCA 较低的亚组中则增加。观察到，在接受促红细胞生成素-β治疗 4 周后，75%的初始 RBCA 较高的贫血患者聚集降低。聚集下降约 34%（p<0.01）。与此同时，25%的研究患者在治疗后 RBCA 显著增加（p<0.05）。用促红细胞生成素-β孵育后，初始 RBCA 较低的红细胞聚集明显增加 122%（p<0.05）。相反，初始 RBCA 降低了 47%（p<0.05）。当 Forskolin（10μM）加入到 RBC 悬液中时，初始 RBCA 较低的亚组中 RBCA 增加，而初始 RBCA 较高的亚组中 RBCA 减少。当 RBC 悬液用长春西汀、钙离子载体（A23187）、佛波醇 12-肉豆蔻酸 13-乙酸酯（PMA）孵育时，观察到类似的 RBCA 变化，这些药物是蛋白激酶 C（PKC）的刺激物。本研究的一个主要发现是，一些药物对红细胞聚集的影响明显取决于患者治疗前的初始聚集状态。这些结果表明，对生物刺激的不同红细胞聚集反应强烈依赖于受试者的初始、治疗前状态，这很可能与环腺苷酸信号通路和 Ca2+调节机制之间的串扰有关。
