Systemic Evaluation of Platelet and Leukocyte Activation and Interaction in a Rat Model of Pulmonary Arterial Hypertension
Systemic Evaluation of Platelet and Leukocyte Activation and Interaction in a Rat Model of Pulmonary Arterial Hypertension
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肺动脉高压大鼠模型中血小板和白细胞活化及相互作用的系统评价
DOI：
10.1159/000320107
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发表时间：
2010-01-01
期刊：
影响因子：
1.9
通讯作者：
Hu, Hu
中科院分区：
文献类型：
--
作者：
Hu, Xiao-Sheng;Du, Chang-Qing;Hu, Hu
目的：血栓形成和炎症与肺动脉高压（PAH）的发病机制相关。然而，没有可靠的数据支持血小板和白细胞的活化和相互作用参与 PAH。因此，本研究研究了野百合碱（MCT）诱导的肺动脉高压大鼠模型中循环血小板和白细胞的激活和相互作用。方法：在注射 MCT（60 mg/kg）前以及注射后 2、3 和 7 周监测大鼠（n = 24）的平均肺动脉压（mPAP）。同时，通过全血流式细胞术测量循环血小板和白细胞的活化以及血小板-白细胞聚集体。结果：注射 MCT 两周后，mPAP 显着升高，即从基线时的 11.25 ± 0.92 mm Hg 升高至 15.71 ± 1.66 mm Hg (p < 0.05)，并且在第 7 周进一步升高 (26.83 ± 3.29 mm Hg；p < 0.01)。注射 MCT 后 3 周，循环血小板的纤维蛋白原结合从基础水平 1.45 ± 0.61 增加至 4.08 ± 1.59% (p < 0.01)。血小板对 ADP 的反应也显着增强。循环中性粒细胞的CD11b表达升高；即平均荧光强度从 MCT 注射前的 1.67 ± 0.38 增加到 MCT 注射后 3 周的 2.37 ± 0.31 (p < 0.01)，并且 N-甲酰基-甲硫氨酰-亮氨酰-苯丙氨酸 (1 × 10–7M) 刺激诱导 MCT 治疗动物中性粒细胞 CD11b 表达更显着升高。与基线 (6.01 ± 2.91%) 相比，MCT 治疗后 2 周循环血小板-中性粒细胞聚集体已增加 (14.93 ± 4.22%; p < 0.01)，并在 3 周时保持升高 (15.19 ± 4.78%; p < 0.01)。结论：MCT诱导的大鼠PAH与体内血小板和白细胞活化增加以及血小板-白细胞相互作用有关，可能在PAH的发病机制中发挥重要作用。
Objectives: Thrombosis and inflammation are associated with the pathogenesis of pulmonary arterial hypertension (PAH). However, there are no solid data supporting the involvement of platelet and leukocyte activation and interaction in PAH. The present study thus investigated the activation and interaction of circulating platelets and leukocytes in a rat model of monocrotaline (MCT)-induced pulmonary hypertension. Methods: Mean pulmonary arterial pressure (mPAP) was monitored in rats (n = 24) before and 2, 3 and 7 weeks after MCT (60 mg/kg)injection. In parallel, activation of circulating platelets and leukocytes and platelet-leukocyte aggregates were measured by whole-blood flow cytometry. Results: Two weeks after MCT injection, mPAP had increased significantly, i.e. from 11.25 ± 0.92 mm Hg at baseline to 15.71 ± 1.66 mm Hg (p < 0.05), and it had increased even further at week 7 (26.83 ± 3.29 mm Hg; p < 0.01). Fibrinogen binding of circulating platelets had increased from the basal level of 1.45 ± 0.61 to 4.08 ± 1.59% 3 weeks after MCT injection (p < 0.01). Platelet responsiveness to ADP was also significantly enhanced. CD11b expression of circulating neutrophils was elevated; i.e. mean fluorescence intensity increased from 1.67 ± 0.38 before MCT injection to 2.37 ± 0.31 3 weeks after MCT injection (p < 0.01), and N-formyl-methionyl-leucyl-phenylalanine (1 × 10–7M) stimulation induced more marked elevation of neutrophil CD11b expression in MCT-treated animals. Circulating platelet-neutrophil aggregates were already increased 2 weeks after MCT treatment (14.93 ± 4.22%; p < 0.01) compared to baseline (6.01 ± 2.91%) and remained elevated at 3 weeks (15.19 ± 4.78%; p < 0.01). Conclusions: MCT-induced PAH in rats is associated with increased platelet and leukocyte activation and platelet-leukocyte interaction in vivo, which may play an important role in the pathogenesis of PAH.