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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 observe the preventive and therapeutic effects of 764-3 on pulmonary vascular wall collagen deposition in rats with chronic hypoxic pulmonary hypertension and to explore its possible mechanism. Methods Male Wistar rats were randomly divided into 10 groups. Hypoxic rats were placed in hypobaric oxygen chamber at 50.7 kPa for 2 or 4 weeks. 764-3 rats were injected subcutaneously at 20 mg / kg once daily. To β-aminopropionitrile (BAPN) rats by 150 mg / kg intraperitoneal injection, 2 times / d. Observe the end of the line hemodynamics, morphology and biochemical indicators. Results The content of hydroxyproline (HYP) in the extrapulmonary pulmonary artery (EPA) of hypoxic rats was significantly increased (P <0.001), while the level of smooth muscle cells (SMCs) in the pulmonary arterioles (IAMA) , The amount of intercellular collagen was significantly increased (P <0.001). 764-3 can significantly reduce the HYP content of EPA (P <0.05-0.001). The structure of SMC in IAMA is reversed, the spermatids are slender and the intercellular collagen is significantly reduced (P <0.001). The effect of inhibiting the deposition of collagen is weak In BAPN (P <0.05). Conclusions It is further confirmed that excessive deposition of collagen plays a very important role in the development and progression of chronic hypoxic pulmonary hypertension, and the recovery of pulmonary hypertension is related to the reversal of collagen and structural changes. The inhibitory effect of 764-3 on pulmonary arterial wall collagen in hypoxic pulmonary hypertension is milder than that of BAPN, which is expected to be used in the prevention and treatment of chronic pulmonary hypertension.