高肺血流肺动脉高压形成机制的研究

Research of pulmonary hypertension induced high pulmonary blood flow in piglet model

目的：研究高肺血流幼猪模型肺动脉血流动力学及组织学变化与血清基质金属蛋白酶、血清内皮素、白细胞介素6、8以及肺组织P38MAPK变化的关联性。方法：采用生后2-3月龄的幼猪,体重7-10 kg,分为两组,每组12只。对照组（control group,n=12）：即假手术组,只开胸无手术处理;高肺血流组（treatment group,n=12）：行左侧开胸,降主动脉与左肺动脉搭桥术。所有动物正常饲养3个月。然后正中开胸,检测肺动脉收缩压（PASP）、肺血管阻力（PVR）,观察肺动脉标本的结构和组织学变化。ELISA检测血清基质金属蛋白酶、血清内皮素、白细胞介素6、8水平、取两组动物的左侧肺脏标本,以免疫印迹方法测量肺组织P38MAPK活性。结果：高肺血流组肺动脉收缩压（PASP）、肺血管阻力（PVR）显著升高（P〈0.01）;左肺动脉出现平滑肌细胞显著增生,部分血管中膜及内膜增厚,管腔狭窄;血清基质金属蛋白酶、血清内皮素、白细胞介素6、8水平升高、肺组织P38MAPK活性升高。结论：在幼猪动物模型中,高肺血流可导致肺动脉结构重塑,可导致肺动脉压力的升高,与血清基质金属蛋白酶、血清内皮素、血浆白细胞介素6、8、肺组织P38MAPK活性变化呈正相关。为进一步研究高肺血流先天性心脏病肺动脉高压的形成过程提供实验依据以及实验平台,以期在治疗上提供新的方法。

Objective：To research the relation of blood serum matrix metalloproteinase 9 （MMP9）, endothelin-1 , IL-6, IL-8, P38MAPK in lung and pulmonary artery pressure and structure in the high pulmonary blood piglet models. Methods： Piglets the age of 2-3 months and weights 7-10 kg were divided into two groups randomly, each group of 12. The only control group （n = 12 ） , or sham group,only that have not been dealt with the operation of the lungs set;high pulmonary blood group （treatment group ,n= 12 ） ： all the line left open, cut to the left pulmonary artery bypass surgery. All animals are normally raise three months, then the open, and testing pulmonary arterial systolic pressure （PASP）and pulmonary vascular resistance（ PVR ）, observing the organization of pulmonary artery; testing MMP9, endothelin-1, IL-6, IL-8, P38MAPK. Results： In shunt group, pulmonary arterial systolic pressure （ pasp ） and pulmonary vascular resistance （ PVR ）significantly increased（ P〈0.01 ） , smooth muscle cells in left pulmonary artery were shown in remarkably, in part of the tunieae intima vasorum thickend. MMP9, endothelin-1, IL-6, IL-8 and P38MAPK significantly increased （ P〈0. 01 ） ; in control group , no apparent change of pulmonary arterial systolic pressure and pulmonary vascular resistance and MMP9, endothelin-1, IL-6,IL-8 and P38MAPK. Conclusion： In piglet models, high lung blood flow could induce the reshaping of the pulmonary artery structure and pulmonary hypertension ,could lead to MMP9 significantly increasing ,endothelin-1, IL-6 ,IL-8 and P38MAPK in lung. To further study the formation of high pulmonary blood flow in congenital heart disease with pulmonary hypertension process provides exper- imental basis, with a view to offer new methods on the treatment.