盐酸妥拉唑林注射液治疗新生儿持续肺动脉高压的临床研究

Clinical trial of tolazolin hydrochloride injection in the treatment of neonatal persistent pulmonary hypertension

目的观察盐酸妥拉唑林注射液治疗新生儿持续肺动脉高压的临床疗效及对血清缺氧诱导因子-1α(HIF-1α)、脂氧合酶同工酶1(LOX1)、内皮素-1(ET-1)的影响。方法将178例新生儿持续肺动脉高压按随机数字表法分为对照组(n=82)和试验组(n=96)。对照组用西那地非治疗,每次0. 5～1. 0mg·kg-1,q6 h,口服或者鼻饲,持续治疗3 d;试验组在对照组基础上给予盐酸妥拉唑林注射液治疗,每次5 mg,qd,皮下注射,持续治疗3 d。比较2组患儿的临床疗效、治疗前后血清HIF-1α、LOX1、ET-1水平和氧合指标变化,及药物不良反应发生情况。结果治疗后,试验组和对照组总有效率分别为90. 62%(87例/96例)和79. 27%(65例/82例),差异有统计学意义(P <0. 05)。试验组和对照组血清HIF-1α水平分别为(305. 75±48. 18)和(371. 05±46. 28)pg·m L^(-1),LOX1水平分别为(0. 50±0. 05)和(0. 59±0. 07)μg·m L^(-1),ET-1水平分别为(43. 51±5. 29)和(72. 03±10. 10) pg·m L^(-1),血二氧化碳分压(PaCO_2)分别为(35. 08±4. 80)和(48. 74±5. 28) mm Hg,血氧分压(PaO_2)分别为(84. 64±11. 78)和(72. 76±8. 86) mm Hg,血氧饱和度(SaO_2)分别为(93. 06±14. 76)%和(89. 06±9. 95)%,差异均有统计学意义(均P <0. 05)。2组药物不良反应以腹泻、寒冷感、出汗为主,对照组和试验组总药物不良反应率分别为8. 54%和13. 54%,差异无统计学意义(P> 0. 05)。结论盐酸妥拉唑林注射液对新生儿持续肺动脉高压的临床疗效确切,可降低血清HIF-1α、LOX1、ET-1水平,改善氧合状态,且未明显增加药物不良反应发生率。

Objective To analyze the clinical efficacy of tolazolin hydrochloride injection in the treatment of neonatal sustained pulmonary hypertension and its effects on serum hypoxia inducible factor-1α( HIF-1α),lipoxygenase isoenzyme 1( LOX1) and endothelin-1( ET-1). Methods A totaol of 178 neonates with persistent pulmonary hypertension were divided into control group( n = 82) and treatment group( n = 96) according to random number table method. Control group was treated with cilostazol,0. 5-1. 0 mg·kg-1 each time,orally or nasally,q6 h,continuous treatment for 3 d. Treatment group was treated with tolazolidine hydrochloride injection on the basis of control group,5 mg each time,qd,subcutaneous injection,continuous treatment for 3 d.Then clinical efficacy,serum levels of HIF-1α,LOX1,ET-1 and oxygenation index change before and after treatment,and adverse drug reactions in two groups were compared. Results After treatment,the total effective rates of treatment group and control group were 90. 62%( 87 cases/96 cases) and 79. 27%( 65 cases/82 cases),with significant difference( P < 0. 05). Serum levels of HIF-1α in treatment group and control group were( 305. 75 ± 48. 18)and( 371. 05 ± 46. 28) pg · m L-1,LOX1 level were( 0. 50 ± 0. 05) and( 0. 59 ± 0. 07) μg·m L-1,ET-1 were( 43. 51 ± 5. 29) and( 72. 03 ± 10. 10) pg · m L-1, blood carbon dioxide partial pressure( PaCO2) were( 35. 08 ± 4. 80) and( 48. 74 ± 5. 28) mm Hg,blood oxygen partial pressure( PaO2) were( 84. 64 ± 11. 78) and( 72. 76 ± 8. 86) mm Hg,blood oxygen saturation( SaO2) were( 93. 06 ± 14. 76) % and( 89. 06 ± 9. 95) %,all with significant difference( all P < 0. 05). The adverse drug reactions in both groups were mainly diarrhea,cold sensation and sweating,while the total adverse drug reactions rate in control group and treatment group were 8. 54% and13. 54%,with no statistical difference( P > 0. 05). Conclusion Tolazolin hydrochloride injection has a definite clinical effect on persistent pulmonary hypertension in neonates,which can reduce serum levels of HIF-1α,LOX1 and ET-1,and improve oxygenation without significantly increasing the incidence of adverse drug reactions.