【摘要】 目的　探讨内皮素 1(ET 1)基因表达变化在慢性低氧 (O2 )高二氧化碳 (CO2 )性肺动脉高压形成中的作用及川芎嗪的影响。方法　将SD大鼠分为正常对照组 (A组 ) ,4周低O2 高CO2 组 (B组 ) ,4周低O2 高CO2 +川芎嗪组 (C组 )。采用透射电镜、图像分析、原位杂交等方法 ,研究 4周低O2高CO2 和川芎嗪对大鼠肺动脉平均压 (mPAP)、颈动脉平均压 (mCAP)、肺细小动脉显微和超微结构ET 1及ET 1基因表达的影响。结果　 (1)B组mPAP与A组比较 ,差异有显著性 (P <0 0 1) ;C组mPAP与B组比较 ,差异有显著性 (P <0 0 1) ,3组间mCAP比较 ,差异无显著性 (P >0 0 5 )。B组血浆ET 1浓度与A组比较 ,差异有显著性 (P <0 0 1) ;C组与B组比较 ,差异有显著性 (P <0 0 1) ;(2 )光镜下肺细小动脉管壁面积 /管总面积比值 (WA/TA)、肺细小动脉中膜平滑肌细胞核密度 (SMC)B组与A组比较 ,差异有显著性 (P均 <0 0 1) ,C组WA/TA、SMC与B组比较 ,差异有显著性 (P均 <0 0 1) ;电镜下 ,B组肺细小动脉中膜平滑肌细胞增生 ,面积增大 ,染色质增多 ,外膜胶原纤维密集 ,C组大鼠肺细小动脉中膜平滑肌细胞和外膜胶原纤维增生与B组比较明显减轻 ;(3)原位杂交发现 ,B组Ⅰ级(直径 >2 0 0 μm)、Ⅱ级 (直径 5 0～ 2 0 0 μm)、Ⅲ级 (直径 <5 0 μm)?更多还原

【Abstract】 Objective To investigate the effects of chronic hypoxic hypercapnia and ligustrazine on expression of endothelin 1 (ET 1) mRNA and the ultrastructure of pulmonary arterioles in rats. Methods Thirty rats were randomly divided into three groups: control group (A), hypoxic hypercapnic group(B), hypoxic hypercapnia+ligustrazine (lig.) group (C). ET 1 mRNA was observed in arterioles from rats by the technique of in situ hybridization. The average value of integral light density (LD) of ET 1 mRNA in pulmonary arterioles was detected by an image analysor and the relative content of ET 1 mRNA was calculated. Results (1) mPAP was significantly higher in rats of B group than that of A group ( P <0.01) and it was much lower in rats of C group than that of B group ( P <0.01). Differences of mCAP were not significant in three groups ( P >0.05); plasma ET 1 concentration was significantly higher in rats of B group than that of A group ( P <0.01), plasma ET 1 concentration was significantly lower in rats of C group than that of B group ( P <0.01); (2) Light microscopy showed that WA/TA (vessel wall area/total area) and SMC (the density of medial smooth muscle cells ) were significantly higher in rats of B group than those of A group ( P <0.01), WA/TA and SMC were significantly lower in rats of C group than those of B group ( P <0.01). Electron microscopy showed proliferation of medial smooth muscle cells and collageous fibers of pulmonary arterioles in rats of B group, and ligustrazine could reverse the changes mentioned above; (3) Hybridization in situ showed that LD of ET 1 mRNA in pulmonary arterioles was significantly higher in rats of B group than that of A group ( P <0.01); LD of ET 1 mRNA in pulmonary arterioles was significantly lower in rats of C group than that of B group ( P <0.01). Conclusions Increase of expression of ET 1 mRNA in pulmonary arterioles contributes to the development of pulmonary hypertension and structural remodeling of pulmonary arteries in chronic hypoxic hypercapnic rats. Ligustrazine can inhibit pulmonary hypertension by decreasing the expression of ET 1 mRNA in pulmonary arterioles.更多还原