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目的研究凋亡相关基因程序性细胞死亡因子4(PDCD4)蛋白在野百合碱诱导肺动脉高压大鼠中的表达并探讨波生坦对其干预机制。方法 SD大鼠正常对照组(N组,n=9),不做任何处理。14只SD大鼠通过腹腔内注射野百合碱(60mg/kg)两周后,随机将大鼠分成2组,肺动脉高压模型对照组(M组,n=7)和波生坦组(B组,n=7),分别通过胃管予以安慰剂或波生坦[200mg/(kg.d)]治疗,每天1次,共3周。测量血流动力学参数,观测肺血管和右室组织病理学改变,Western blot法测定肺组织中PDCD4和p-ERK1/2蛋白的表达。结果与N组相比,M组大鼠肺组织PDCD4蛋白表达明显减少、p-ERK1/2蛋白表达明显增加(P均<0.001)。与M组相比,B组的平均肺动脉压和肺小动脉中膜平滑肌厚度均明显减少,肺组织PDCD4蛋白表达明显增加、p-ERK1/2蛋白表达明显减少(P均<0.01)。结论 PDCD4蛋白在野百合碱诱导肺动脉高压大鼠中的表达减少,而波生坦可能经p-ERK1/2信号途径增加PDCD4蛋白表达从而降低肺动脉高压、减轻血管平滑肌细胞增殖,逆转肺血管重构的发生。
Objective To study the expression of apoptosis-related gene programmed cell death factor 4 (PDCD4) in monocrotaline-induced pulmonary hypertension in rats and explore the mechanism of bosentan intervention. Methods SD rats normal control group (N group, n = 9), without any treatment. Fourteen Sprague-Dawley rats were randomly divided into two groups after intraperitoneal injection of monocrotaline (60 mg / kg) for two weeks. The pulmonary hypertension model control group (M group, n = 7) and bosentan group , n = 7) were given placebo or bosentan [200 mg / (kg · d)] by gastric tube once a day for 3 weeks. The parameters of hemodynamics were measured and pathological changes of pulmonary vessels and right ventricle were observed. The expression of PDCD4 and p-ERK1 / 2 protein in lung tissue were detected by Western blot. Results Compared with N group, the expression of PDCD4 protein and the expression of p-ERK1 / 2 in lung tissue of M group were significantly decreased (all P <0.001). Compared with M group, mean pulmonary arterial pressure and pulmonary arterial smooth muscle thickness were significantly decreased in group B, the expression of PDCD4 protein and the expression of p-ERK1 / 2 in lung tissue were significantly decreased (all P <0.01). Conclusions PDCD4 protein is decreased in monocrotaline-induced pulmonary hypertension rats, while bosentan may increase the expression of PDCD4 protein via p-ERK1 / 2 signaling pathway, thereby reducing pulmonary hypertension, decreasing the proliferation of vascular smooth muscle cells and reversing the remodeling of pulmonary vascular remodeling occur.