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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，mRVP）、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mRVP 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mRVP，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。

英文摘要:

Objective:To study the effects of CXCC hemokine receptor-4 (CXCR4) inhibitor (AMD3100) on hypoxia-induced pulmonary hypertension in rats.Methods:Fifteen rats randomly received one of the following treatments: normoxia control, 4 w hypoxia and 4 w hypoxia+AMD3100. The rats were exposed to low-pressure and low-oxygen condition in an auto-modulating hypobaric and hypoxic cabin (air pressure 55 kPa, oxygen concentration 10 %) to establish hypoxic pulmonary hypertension (HPH) animal model. After 4 weeks of chronic hypoxia, the expression of CXCR4, dynamics of blood flow index, right ventricular hypertrophy index and histopathological changes were detected. To extract and identify primary culture rat pulmonary arterial smooth cells (PASMCs), cell migration and proliferation were observed by treating with hypoxia and AMD3100.Results:①The expression of CXCR4 were increased in lung tissue of hypoxic rats, mean right ventricular pressure (mRVP), right ventricular hypertrophy index (Right ventricle/Left ventricle plus septum, RV/BW; Right ventricle/Body weight, RV/(LV+S)) were also increased, and small pulmonary artery wall became thicker, suggesting that building model successful; mRVP, RV/BW, RV/(LV+S) and small pulmonary artery wall of hypoxia+AMD3100 rats were decreased significantly compared with the hypoxia group(P<0.05). ②The PASMCs of hypoxia group migration and proliferation were increased compared with normoxic group; the hypoxia+AMD3100 group migration and proliferation were inhibited obviously compared with the hypoxia group (P<0.05).Conclusion:AMD3100 could effectively reduce mRVP and inhibit the proliferation of small pulmonary artery wall to reduce right ventricular hypertrophy in hypoxic pulmonary hypertension rats, which may be by inhibiting the PASMCs migration and proliferation, thereby inhibiting pulmonary vascular reconstruction, playing a role in prevention of hypoxic pulmonary hypertension.

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