CXCR4抑制剂AMD3100对大鼠低氧性肺动脉高压作用的实验研究

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目的:研究CXC趋化因子受体-4(CXC Chemokine receptor-4,CXCR4)的抑制剂(AMD3100)对大鼠低氧性肺动脉高压的影响。方法:将实验动物随机分为常氧对照组、低氧组、低氧+AMD3100组,采用低压低氧法建立大鼠低氧性肺动脉高压模型,4周后观察低氧对CXCR4表达的影响及各组大鼠血流动力学、右心室肥厚指标和组织病理学改变。培养原代大鼠肺动脉平滑肌细胞(Pulmonary arterial smooth cells,PASMCs),分别低氧处理及给予AMD3100,观察细胞迁移、增殖情况。结果:1低氧组大鼠CXCR4表达增加,右心室压力(Mean right ventricle pressure,m RVP)、右心室肥厚指标(Right ventricle/Body weight,RV/BW;Right ventricle/Left ventricle plus septum,RV/(LV+S))增加,肺细小动脉管壁增厚,造模成功;低氧+AMD3100组大鼠m RVP和RV/BW、RV/(LV+S)比值、肺细小动脉管壁增厚程度较低氧组明显降低(P<0.05)。2低氧组PASMCs与常氧组相比,细胞迁移及增殖均明显增加;AMD3100组PASMCs迁移和增殖与低氧组相比受抑制(P<0.05)。结论:AMD3100能有效的降低大鼠低氧性肺动脉高压的m RVP,抑制肺细小动脉管壁的增生,减轻右心室的肥厚,其有可能是通过抑制了PASMCs的迁移和增殖,从而抑制肺血管的重建,防治低氧性肺动脉高压。 AIM: To investigate the effects of CXCR4 inhibitor CXCR4 on hypoxic pulmonary hypertension in rats. Methods: Experimental animals were randomly divided into normoxia control group, hypoxia group, hypoxia + AMD3100 group. Hypoxic hypoxic pulmonary hypertension model was established by hypobaric hypoxia. The effect of hypoxia on CXCR4 expression was observed after 4 weeks. Hemodynamics, right ventricular hypertrophy index and histopathological changes of rats in each group. Primary rat pulmonary artery smooth muscle cells (PASMCs) were cultured and hypoxic treated with AMD3100 respectively. The migration and proliferation of the cells were observed. (1) The expression of CXCR4 in hypoxia group was significantly higher than that in control group (P <0.05) .Conclusion: 1 The expression of CXCR4 in right hypoxia group increased, RVV, (LV + S)), thickening of pulmonary arteriole wall and successful modeling. The ratio of m RVP, RV / BW and RV / (LV + S) The degree of oxygen group was significantly lower (P <0.05). Compared with normoxia group, the migration and proliferation of PASMCs in hypoxia group were significantly increased. The migration and proliferation of PASMCs in AMD3100 group were inhibited compared with those in hypoxia group (P <0.05). Conclusion: AMD3100 can effectively reduce the m RVP of hypoxic pulmonary hypertension, inhibit the proliferation of pulmonary arteriole wall and reduce the hypertrophy of right ventricle, which may inhibit the migration and proliferation of PASMCs, thereby inhibiting the pulmonary vascular Reconstruction, prevention and treatment of hypoxic pulmonary hypertension.
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