【摘要】 目的:探讨塞来昔布对慢性低O2高CO2大鼠肺动脉高压的作用。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+塞来昔布组。用电镜、放免等方法,观察各组大鼠肺动脉平均压、颈动脉平均压、肺细小动脉显微结构、血浆和肺匀浆血栓素B2(TXB2)及6-酮-前列腺素F1α(6-keto-PGF1α)含量的变化。结果:①慢性低O2高CO2组平均肺动脉压(mPAP)比正常组显著升高,塞来昔布组的mPAP比慢性低O2高CO2组显著升高,3组间平均颈动脉压(mCAP)比较差异无显著性。②慢性低O2高CO2组与正常对照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;塞来昔布组与慢性低O2高CO2组相比血浆和肺匀浆TXB2浓度无明显变化、TXB2/6-keto-PGF1α显著升高,6-keto-PGF1α显著下降。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。塞来昔布组与慢性低O2高CO2组相比WA/TA和PAMT显著增高。④电镜下慢性低O2高CO2组大鼠肺细小动脉内皮细胞吞饮小泡增多,血管壁增厚,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;塞来昔布组中膜平滑肌细胞增大、增多,胞浆肌丝丰富,平滑肌细胞间隙增宽,肺泡隔胶原纤维增生明显。结论:塞来昔布可能有加重慢性低O2高CO2性肺动脉高压和肺血管结构重建倾向,过度抑制COX-2,使TXA2/PGI2比值升高可能是其作用机制之一。更多还原

【Abstract】 Objective: To study the effect of celecoxib on chronic hypoxia and hypercapnic pulmonary hypertension.Methods: SD rats were randomly divided into normal control group(A),hypoxic hypercapnic group(B),hypoxic hypercapnia+ celecoxib group(C).The content of TXB2 and 6-keto-PGF1α in plasma and lung were detected by the technique of radioimmunology.Results: ①Mean pulmonary arteria pressure(mPAP) was significantly higher in rats of B group than those of A group.mPAP was significantly higher in rats of C group than those of B group.Differences of mPAP were not significant in three groups.②The content of TXB2 in plasma and lung and the ratio of TXB2/6-keto-PGF1α were significantly higher in rats of B group than those of A group.The ratio of TXB2/6-keto-PGF1α was significantly higher and the content of 6keto-PGF1α in plasma and lung was significantly lower in rats of C group than those of B group.③Light microscopy showed that WA/TA(vessel wall area/total area) and PAMT(the thickness of medial smooth cell layer) were significantly higher in rats of B group than those of A group.WA/TA and PAMT were significantly higher in rats of C group than those of B group.④Electron microscopy showed the thickening of vessel wall and the proliferation of collagen fiber in B group and augmentation of smooth muscle cell and abundance of myofilament in pulmonary arterioles in C group.Conclusion: Celecoxib can aggravate hypoxic hypercapnia pulmonary hypertension and pulmonary vessel remodeling by increasing the ratio of TXA2/ PGI2.更多还原