硼替佐米对大鼠肺动脉高压血管重构及基质金属蛋白酶-9的影响

Effect of bortezomib on vascular remodeling and expression of matrix metailo proteinases-9 in pulmonary arterial hypertension rats

目的:研究硼替佐米对肺动脉高压诱导的肺血管重构的影响,并探讨其可能作用机制。方法:采用外科手术方法建立左向右分流型肺动脉高压模型。18只大鼠随机分为对照组、模型组、硼替佐米组,每组6只。彩色多普勒超声测量并记录血流动力学参数,称重比较右心室肥厚指数的变化。HE染色观察肺血管病理形态改变,免疫组织化学法检测肺动脉增殖细胞核抗原(PCNA)及基质金属蛋白-9(MMP-9)表达的变化。结果:硼替佐米干预能明显改善心肺血流动力学参数,抑制肺动脉高压诱导的肺血管重构(P<0.05)。免疫组织化学结果提示PCNA与MMP-9阳性表达明显减少(P<0.05)。结论:硼替佐米能明显改善高血流型肺动脉高压肺脏功能,有效抑制肺血管重构,其机制可能与抑制MMP-9活性有关。

Objective To observe the effect of bortezomib on vascular remodeling in pulmonary arterial hypertension （PAH） rats and to explore the mechanism. Methods A left-to-right shunt PAH models were established by surgical operation. Eighteen male Wister rats were randomly divided into control, model and treatment with bortezomib group （n = 6 in each group）. The hemodynamics datas were detected by echocardiography. The right ventricular hypertrophy index was compared by weight. Pathological morphology of pulmonary vessels were observed by HE stain. Proliferating cell nuclear antigen （PCNA） and matrix metailo proteinases-9 （MMP-9） in pulmonary artery smooth muscle cells were determined by immunohistochemistry. Results Treatment with bortezomib could significantly improve the hemodynamics data, inhibit vascular remodeling induced by PAH. The positive expression of PCNA and MMP-9 significantly decreased （P 〈 0.05）. Conclusion Bortezomib obviously improved puhnonary function of the high blood type PAH, effectively inhibit pulmonary vascular remodeling, the mechanism may be related to inhibiting the activity of MMP-9.