血红素氧合酶1基因表达与慢性低氧高二氧化碳性肺动脉高压的关系

Relationship between expression of heme oxygenase-1 mRNA and pulmonary hypertention induced by hypoxic hypercapnia

目的 :研究一氧化碳体系对低氧高二氧化碳性肺动脉高压的调控作用。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 +血晶素组 (C组 )。采用透射电镜、图像分析、免疫组化、组织原位杂交技术等方法 ,观察各组大鼠肺动脉平均压 (mPAP)、颈动脉平均压 (mCAP)、右心室 / (左心室 +室间隔 )重量比 [RV/ (LV +S) ]、肺细小动脉显微和超微结构、血CO浓度及肺细小动脉HO - 1及其基因表达的变化。结果 :①B组mPAP、RV/ (LV +S)显著高于A组 (P <0 0 1) ,C组mPAP、RV/ (LV +S)明显低于B组 (P <0 0 1) ,3组间mCAP比较差异无显著性 (P >0 0 5 )。②全血CO浓度B组明显高于A组 (P <0 0 1) ,C组明显高于B组 (P <0 0 1)。③光镜下肺细小动脉管壁面积 /管总面积 (WT/TA)、肺细小动脉中膜平滑肌细胞核密度 (SMC)、肺细小动脉中膜厚度(PAMT)B组显著高于A组 (P <0 0 1) ,C组明显低于B组 (P <0 0 1)。④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明显轻于B组。⑤免疫组化、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)肺细小动脉HO - 1及HO -

AIM: To study the effect of chronic hypoxic hypercapnia on expression of heme oxygenase-1(HO-1). METHODS: Sprague-Dawley rats were randomly divided into three groups: control group(A),hypoxic hypercapnic group(B), hypoxic hypercapnia+hemin group(C). HO-1 and HO-1 mRNA were observed in pulmonary arterioles by the technique of immunohistochemistry and in situ hybridization. RESULTS: ① mPAP and weight ratio of right ventricle(RV) to left ventricle plus septum (LV+S) were significantly higher in rats of B group than those of A and C group (P<0.01). Differences of mCAP were not significant in three groups(P>0.05). ② Blood CO concentration was significantly higher in rats of B group than that of A group(P<0.01), it was much higher in C group than that of B group(P<0.01). ③ Light microscopy showed that vessel well area/total area (WA/TA), density of medial smooth muscle cell (SMC) and media thickness of pulmonary arterioles were much higher in rats of B group than those of A and C group(P<0.01). ④ The observation by electron microscopy showed proliferation of medial smooth muscle cells and collageous fibers of pulmonary arterioles in rats of B group, hemin could reverse the changes mentioned above. ⑤ HO-1 and HO-1 mRNA in pulmonary arterioles was significantly higher in rats of B group than those of A group(P<0.01), and they were significantly higher in rats of C group than those of B group(P<0.01). CONCLUSION: Expression of HO-1 mRNA and HO-1 in pulmonary arterioles was enhanced by hypoxic hypercapnia. Hemin partly inhibited pulmonary hypertension and pulmonary vessel remodeling by enhancing the expression of HO-1 mRNA and HO-1.