知母宁对慢性低O_2高CO_2大鼠肺动脉高压的影响及其机制研究

EFFECT AND MECHANISM OF CHIMONIN ON PULMONARY HYPERTENTION OF CHRONIC HYPOXIA AND HYPERCAPNIC RATS

目的 :研究知母宁对慢性低氧高二氧化碳性肺动脉高压的抑制作用及其作用机制。方法 :将SD大鼠分为正常对照组 ,4周低O2 高CO2 组 ,4周低O2 高CO2+知母宁组 (知母宁组 )。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)、肺细小动脉显微和超微结构、血CO浓度、血红素氧合酶 1(HO 1)及其基因表达的变化。结果 :①低O2 高CO2 组mPAP比正常组显著增高 ,知母宁组mPAP比低O2 高CO2 组显著降低 ;3组间mCAP比较差异无显著性。②全血CO浓度低O2 高CO2 组比正常组显著增高 ,知母宁组比低O2 高CO2 组增高。③光镜下低O2 高CO2 组与正常组相比 ,肺细小动脉管壁面积 管总面积、肺细小动脉中膜平滑肌细胞核密度、肺细小动脉中膜厚度均显著升高 ,知母宁组与低O2 高CO2 组相比以上指标显著降低。④电镜下知母宁组肺细小动脉中膜平滑肌细胞增生、面积增大、染色质增多、外膜胶原纤维增生均较低O2高CO2 组明显减轻。⑤免疫组化、原位杂交发现低O2 高CO2 组大鼠肺细小动脉HO 1及mRNA与正常组比较均明显增加 ,知母宁组大鼠肺细小动脉HO 1及mRNA表达均较低O2 高CO2 组为高。结论 :知母宁有抑制慢性低氧高二氧化碳性肺动脉高压和肺血管结构重建的作用 ,上?

Aim: To study the effect of chimonin on chronic hypoxia and hypercapnic pulmonary hypertention and to explore its mechanism. Methods: SD rats were randomly divided into normal control group(A),hypoxic hypercapnic group(B), hypoxic hypercapnia+chimonin group(C). HO-1 and HO-1 mRNA was observed in pulmonary arterioles of rats by the technique of immunohistochemistry and in situ hybridization. Results: ①mPAP was significantly higher in rats of B group than that of A and C group.Differences of mCAP were not significant in three groups. ②Blood CO concentration was significantly higher in rats of B group than that of A group, it was significantly higher in rats of C group than that of B group. ③Light microscopy showed that WA/TA(vessel wall area/total area)?SMC(the density of medial smooth muscle cell) and PAMT(the thickness of medial smooth cell layer) were significantly higher in rats of B group than those of A and C group. ④Electron microscopy showed proliferation of medial smooth muscle cells and collagenous fibers of pulmonary arterioles in rats of B group, and chimonin 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 that of A group, they were significantly higher in rats of C group than that of B group. Conclusion: Chimonin can inhibit hypoxic hypercapnia pulmonary hypertension and pulmonary vessel remodeling by further increasing the expression of HO-1 mRNA.