764-3对慢性缺氧性肺动脉高压大鼠肺血管壁胶原沉积的防治作用  

Effects of 764-3 on Collagen Deposition in Hypertensive Pulmonary Arteries in Hypoxic Rats

作　　者：柳志红[1] 程显声[1] 蔡如升 孙本韬[2] 朱宜明 李亚辉[1] 

机构地区：[1]中国医学科学院,中国协和医科大学,阜外心血管病医院,北京100037 [2]山西医学院电镜室

出　　处：《中国医学科学院学报》1998年第3期197-202,共6页Acta Academiae Medicinae Sinicae

基　　金：国家自然科学基金(39070404)

摘　　要：目的观察764-3对慢性缺氧性肺动脉高压大鼠肺血管壁胶原沉积的防治作用,并探讨其可能的作用机制。方法将雄性Wistar大鼠随机分为10组。缺氧大鼠置于50.7 kPa低压氧舱内2或4周。给764-3大鼠按20 mg/kg皮下注射,1次/d。给β-氨基丙腈(BAPN)大鼠按150 mg/kg腹腔注射,2次/d。观察终点行血流动力学、形态及生化指标测定。结果缺氧大鼠肺外肺动脉(EPA)羟脯氨酸(HYP)含量显著增高(P<0.001),肺腺泡内肌型动脉(IAMA)中膜平滑肌细胞(SMC)肥大、呈分泌型改变,细胞间胶原量明显增加(P<0.001)。764-3能显著降低EPA的HYP含量(P<0.05～0.001),IAMA中膜SMC结构逆转,胞体多细长,细胞间胶原明显减少(P<0.001);其抑制中膜胶原沉积的作用弱于BAPN(P<0.05)。结论进一步证实在慢性缺氧性肺动脉高压发生、发展过程中,胶原过度沉积起着非常重要作用,而肺动脉高压的恢复与胶原及结构变型的逆转有关。764-3对缺氧性肺动脉高压肺动脉壁胶原的抑制作用较BAPN温和,可望用于慢性肺动脉高压的防治。Objective To investigate the changes of collagen deposition in pulmonary arteries in chronic hypobaric hypoxic rats and the roles of 764-3. Methods Wistar rats were devided into 10 groups. The hypoxic (50. 7 kPa) rats were treated with 764-3 (20 mg/kg, once daily) and β-aminopropionitrile (BAPN, 150 mg/kg, twice daily), respectively. At the end of treatment, the hemodynamic、morphological and chemical parameters were measured. Results Comparing with the normals, hydroxyproline (HYP) content of extrapulmonary artery (EPA) increased obviously in hypoxic rats, the smooth muscle cells (SMC) in the media of muscular intra-acinar pulmonary artery showed hypertrophy with change in phenotype, and a striking increment of collagen accumulation (P<0.001); 764-3 could reduce HYP content of EPA(P<0.05～0.001), and most of SMC in the media became thin and elongated with reversion of change of SMC phenotype, and collagen accumulation was reduced (P<0.001). In addition, BAPN was more effective than 764-3 (P<0.05). Conclusions Excessive collagen accumulation in pulmonary arteries plays an important role in the maintenance of hypoxic pulmonary hypertension. 764-3 can partially inhibit collagen deposition in pulmonary arteries, attenuate hypoxic pulmonary hypertension, and has a moderate influence on collagen deposition in compared with BAPN.

关 键 词：肺动脉高压 缺氧 胶原 764-3 防治 

分 类 号：R543.201[医药卫生—心血管疾病]