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大鼠原发性肺动脉高压模型中循环血小板和白细胞的活化及其作用
Contribution of circulating platelet and leukocyte activation to primary pulmonary hypertension in rats
【摘要】 目的:探讨循环血小板和白细胞活化在原发性肺动脉高压发生发展中的作用。方法:雄性Sprague-Dawley(SD)大鼠皮下注射2%野百合碱(MCT)以建立原发性肺动脉高压模型。采用流式细胞术检测3周末(MCT3W组)模型组和正常对照组大鼠全血血小板纤维蛋白原结合率、白细胞活化标志物CD11b的表达以及血小板与白细胞聚集体的形成。结果:大鼠注射MCT 3周后,右心室收缩压、平均肺动脉压均较正常对照明显上升(P<0.01),而平均动脉压和心率无统计学差异(P>0.05)。大鼠肺标本Masson三色染色显示肌性小肺动脉中膜严重增厚。血小板纤维蛋白原结合率MCT3W组较对照组高[(4.08±1.59)%vs(1.45±0.61)%,P<0.01]。MCT3w组除淋巴细胞亚群外,中性粒细胞和单核细胞亚群CD11b表达的平均荧光强度较对照组显著增加(P<0.01)。MCT3w组的血小板-中性粒细胞聚集体形成较对照组均明显增多(P<0.01)。结论:在大鼠原发性肺动脉高压模型中,循环血小板和白细胞的活化可能促进肺动脉高压的发生和病理生理改变。
【Abstract】 Objective: To evaluate the contribution of platelet and leukocyte activation in pathogenesis primary pulmonary hypertension(PPH).Methods: Pulmonary hypertension was induced by subcutaneous injection of 2% monocrotaline(MCT) in male Prague-Dawley(SD) rats.Blood samples were collected at the third week after MCT injection,and flow cytometry was used to determine the fibrinogen-binding platelet,CD11b expression on leukocyte and platelet-leukocyte aggregation.Results: Three weeks after MCT injection,rats exhibited higher right ventricular systolic pressure(RVSP) and mean pulmonary artery pressure(mPAP),as compared with controls.MCT induced vascular remodeling characterized by vascular medial wall thickening in pulmonary muscular arteries.The ratio of platelets fibrinogen binding was increased in rats 3 weeks after MCT injection than that of control group [(4.08±1.59)% vs(1.45±0.61)%,P<0.01].CD11b expression in monocytes and neutrophils,but not in lymphocytes was increased significantly 3 weeks after MCT injection(P<0.01).Platelet-neutrophil aggregations increased in MCT injected rats as compared with controls(P<0.01).Conclusion: Rats of PPH model demonstrate enhanced circulating platelet and leukocyte activation,which may contribute to the pathogenesis of PPH.
【Key words】 Hypertension,pulmonary; Blood platelets; Leukocytes; Thromboxane B2/blood; Disease models,animal; Fibrinogen/blood; Inflammation;
- 【文献出处】 浙江大学学报(医学版) ,Journal of Zhejiang University(Medical Sciences) , 编辑部邮箱 ,2008年03期
- 【分类号】R543
- 【被引频次】3
- 【下载频次】158