雾化吸入一氧化氮供体硝普钠治疗新生猪急性呼吸窘迫综合征的实验研究

Experimental Study on Nebulized Nitrogen Monoxidum Donator Sodium Ni troprusside on Acute Respiratory Distress Syndrome in Newborn Piglets

目的探讨雾化吸入(neb)一氧化氮(NO)供体硝普钠(SNP)(neb-SNP)对新生猪急性呼吸窘迫综合征(ARDS)的疗效、安全性及实验依据。方法采用生理盐水(NS)肺泡灌洗法复制ARDS新生猪模型(n=30)。造模成功后将其随机分成5组(n=6×5)。对照组:仅机械通气治疗;NS组:机械通气治疗+neb-NS30min治疗;A,B和C组为实验组,分别进行机械通气治疗+neb-SNP1mg/mL,5mg/mL和10mg/mL30min治疗。对5组分别于不同时点进行动态平均股动脉压(MAP)、平均肺动脉压(MPAP)、全血高铁血红蛋白(MetHb)含量监测及动脉血气分析和细胞因子[肿瘤坏死因子(TNF)-α与白细胞介素(IL)-10,-12]水平测定。结果造模成功时,NS组及A,B,C组MPAP均显著高于对照组,差异有统计学意义(P<0.01);neb结束时,B及C组MPAP较NS组显著下降,差异有统计学意义(P<0.05)。在相同时点,5组MAP比较,差异无统计学意义(P>0.05)。neb结束时,5组全血MetHb含量比较,差异无统计学意义(P>0.05)。A,B及C组neb结束后30min,未发现反跳性肺动脉高压。neb结束后不同时点,A,B及C组与对照组及NS组IL-10,-12,TNF-α比较,差异有统计学意义(P<0.05),而B与C组比较,差异无统计学意义(P>0.05)。结论 neb-SNP可选择性降低ARDS模型肺动脉高压,同时具有调节炎症介质和抗炎因子等作用,可抑制炎症因子表达,从而减轻ARDS症状。

Objective To observe the effects of nebulized（neb） nitrogen monoxidum（NO） donors sodium nitroprusside（SNP）（neb-SNP）on acute respiratory distress syndrome（ARDS） in newborn piglets.Methods Thirty anesthetized and mechanically ventilated piglets were randomly divide d into five groups（n=6×5）：①Control group;②Group NS,receiving neb normal sodium（NS） after ARDS ;③ Group A,B,and C（neb-SNP）,receiving 1 mg/mL,5 mg/mL an d 10 mg/mL neb-SNP after ARDS,respectively.Mean arterial pressure（MAP） and me an pulmonary a rterial pressure（MPAP） were monitored continuously.Arterial blood gas analysis was determined at baseline,termination of neb-SNP and 30 min,60 min,120 min after neb,and blood methemoglobin（MetHb） were monitored.Tumor necrosis factor（TNF）-α,interleukin（IL）-10,-12 concentration in serum at 30 min,60 min and 120 min after neb were measured.Results ARDS resulted in a significan t increase in MPAP,MPAP in group NS,group A,B and C were significantly higher than th at in control group（P0.01）.After neb,MPAP in group B and C were significantly lower than that in group NS（P0.05）.There was no significant differe nce in MAP among five groups at the same time points（P0.05）.After neb,th ere were no significant differences in blood MetHb level among five groups.No r ebound pulmonary hypertension was observed after withdrawal of neb.Serum concen trations of TNF-α and IL-12 in group A,B and C（the neb-SNP treated group） were more decreased than those in control group and group NS,and serum IL-10 c oncentration was obviously increased in group A,B and C.Conclusions neb-SNP could be used as a selective pulmonary vasodilator for acute p ulmonary hypertension induced by ARDS in newborn piglets.Reduced lung injury in duced by ARDS through lowering and inhibiting expression of harmful inflammatory cytokines.