红花注射液对慢性低O_2高CO_2肺动脉高压大鼠COX-2 mRNA和蛋白表达的影响

Effect of safflower injection on expression of COX-2 mRNA and protein in chronic hypoxic hypercapnic rat pulmonary arterioles

目的:探讨红花注射液对慢性低O2高CO2肺动脉高压大鼠环氧酶-2(COX-2)基因表达的影响。方法:将SD大鼠分为正常对照组、慢性低O2高CO2组、慢性低O2高CO2+红花注射液组。用原位杂交、电镜、放射免疫测定等方法,观察各组大鼠肺动脉平均压(mPAP)、肺细小动脉显微结构、肺动脉COX-2基因及蛋白表达、血浆和肺匀浆血栓素B2(TXB2)和6-酮-前列腺素(6-keto-PGF1α)含量的变化。结果:①慢性低O2高CO2组mPAP显著高于正常组,红花注射液组的mPAP显著低于慢性低O2高CO2组,3组间平均颈动脉压(mCAP)无显著差异。②慢性低O2高CO2组与正常对照组组相比血浆和肺匀浆TXB2浓度、TXB2/6-Keto-PGF1α比值显著增高,6-Keto-PGF1α浓度显著下降;红花注射液组与慢性低O2高CO2组相比血浆和肺匀浆TXB2浓度、TXB2/6-Keto-PGF1α显著下降,6-Keto-PGF1α显著升高。③光镜下慢性低O2高CO2组与正常组相比,肺细小动脉管壁面积/管总面积(WA/TA)和肺细小动脉中膜厚度(PAMT)均显著增高;电镜下显示肺细小动脉中膜平滑肌细胞增生,纤维细胞增多,肺泡II型上皮细胞微绒毛脱落;红花注射液组WA/TA和PAMT显著降低;肺细小动脉中膜平滑肌细胞增生减轻,纤维细胞少,胶原纤维减少,肺泡II型上皮细胞微绒毛丰富、结构清楚。④红花注射液组与慢性低O2高CO2组相比,COX-2基因与蛋白表达明显增强,而COX-1表达无明显变化。结论:肺动脉COX-2基因表达增强可能是红花注射液减轻慢性低O2高CO2性肺动脉高压和肺血管结构重建的重要机制之一。

AIM ： To study the effect of safflower injection on expression of COX - 2 mRNA in chronic hypoxie hypereapnie rat pulmonary arterioles. METHODS ： Sprague - Dawley rats were randomly divided into normal control group, hypoxie hypereapnie group （B）, hypoxie hypereapnia ＋ safflower injection group （C）. The concentration of TXB2 and 6 - Keto - PGF1α in plasma and in lung were detected by the technique of radioimmunoassay. COX - 2 mRNA was observed in arterioles from rats by the technique of in situ hybridization. RESULTS： （1） Mean pulmonary arterial pressure（mPAP） , weight ratio of right ventricle （RV） to left ventricle plus septum （LV ＋ S） were much-higher in B group than those in control group. No significant difference of mean carotid arterial pressure（reCAP） was observed in three groups. （2） The concentration of TXB2 and the ratio of TXB2/6 - keto - PGF1α were significantly higher in B group than those in control group. （3） Light microscopy showed that vessel wall area/total area, the density of medial smooth muscle cells and the thickness of medial smooth cell layer were significantly higher in B group than those in control group. Electron microscopy showed proliferation of medial smooth muscle cells and collagenoas fibers in pulmonary arterioles in B group. Safflower injection reversed the changes mentioned above. （4） Expression of COX - 2 mRNA in pulmonary arterioles was much higher in C group than those in B group. Differences of COX - 1 mRNA in pulmonary arterioles were not significant between these two groups. CONCLUSION： Safflower injection increases the expression of COX -2 mRNA in chronic hypoxie hypereapnie rat pulmonary arterioles, indicating an important mechanism that safflower injection inhibits the formation of hypoxic hypercapnia pulmonary hypertension and pulmonary vessel remodeling.