盐酸戊乙奎醚对急性肺损伤血管内皮保护作用的临床研究

Clinical study on PHC for pulmonary endothelial protection in acute lung injury

目的观察选择性抗胆碱药盐酸戊乙奎醚(PHC)对急性肺损伤(ALI)患者的治疗效果及其对血清中炎性递质血管内皮生长因子(VEGF)、内皮素-1(ET-1)、血管内皮损伤标志物血管性假血友病因子(vWF)变化的影响。方法42例ALI患者随机分为PHC治疗实验组和常规治疗对照组。观察两组48小时内临床疗效;动脉血气;酶联免疫吸附法(ELISA)测定血清VEGF,ET-1,vWF的变化趋势。结果治疗后两组PaO2、PaO2/F iO2均逐渐升高,实验组提前至6小时与0小时组内相比有改善(P<0.05),24、48小时PaO2、PaO2/F iO2实验组改善优于对照组(P<0.05)。PHC显著降低血清VEGF、ET-1、vWF血清浓度,48小时较0小时下降均有统计学差异(P<0.05),且48小时实验组较对照组改善显著(P<0.05),vWF在48小时存活组与死亡组比较有统计学差异(P<0.05)。结论PHC能够改善ALI患者早期血气指标,降低VEGF、ET-1和vWF血清浓度;氧合作用的改善可能是由于降低了血管炎性递质VEGF、ET-1所产生;实验组血管损伤标记物vWF的下降,提示PHC可能起到保护肺血管内皮细胞完整性的作用,对早期急性肺损伤有一定的治疗作用。

Objective To observe the effects of an anticholinergic agent penehyclidine hydrochloride （ PHC ） in treating acute lung injury（ALl） and its effects on changes of vascular endothelial growth factors （VEGF） , ET-1 and vWF and to investigate the protective mechanism of PHC on vascular endothelial injury. Methods The 42 patients with ALl were randomly divided into two groups： PHC treatment group（ experimental group, n = 21 ）and routine treatment group （ control group, n = 21 ）. Clinical symptoms, respiratory rate, heart rate, PaO2 and PaO2/FiO2 were observed for 48 hours. VEGF, ET-1 , vWF were measured at 0,6,12,24,48 hours respectively. Results PaO2 and PaO2/FiO2 improved gradually after treatment. PaO2 and PaO2/FiO2 at 6 hours were increased compared with those at 0 hour（ P 〈 0.05） in experimental group. PHC significantly decreased VEGF, ET-1, vWF,which decreased obviously at 48 hours compared with those at 0 hour（ P 〈 0.05 ）. At 48 hours, VEGF, E FI, vWF in experimental group decreased more than those in control group （ P 〈 0.05 ） , and vWF had statistical difference between survior group and death group. Conclusion PHC can improve PaO2 and PaO2/FiO2 ,decrease plasma concentration of VEGF,ET-1 and vWF. This effect may arise from down-regulating VEGF, ET-1 and vWF. The decrease of the marker of vascular endothelial injury--vWF in experimental group indicates that PHC may protect integration of pulmonary microvascular endothelial ccll and treat acute lung injury.