参附注射液联合去甲肾上腺素对脓毒症休克兔舌下微循环的影响

目的:观察参附注射液联合去甲肾上腺素对脓毒症休克兔舌下微循环的影响。方法:30只新西兰兔,随机分为5组:假手术组(Sham组)、模型组(Model组)、去甲肾上腺素组(NE组)、参附注射液组(SFI组)和参附注射液联合去甲肾上腺素组(SFI+NE组),每组各6只。Sham组只进行相应手术操作,不进行造模处理,其余各组经兔耳缘静脉注射脂多糖(LPS,2mg/kg)建立脓毒症休克模型,模型复制成功后给予乳酸钠林格注射液30ml/kg补液1h。NE组在模型建立后通过微量注射泵以2.0μg/kg/min的速度给予去甲肾上腺素(40μg/ml)6h;SFI分别于造模前、休克时、休克后1h和休克后2h给予参附注射液(2.5ml/kg)。SFI+NE组同时按NE组和SFI组处理方法进行干预;Model组和Sham组在模型建立后给予等体积的生理盐水(分6h持续泵入)。各组动物于建模前、休克时以及休克后1h、3h和6h时通过电生理记录仪和舌下微循环成像系统分别采集平均动脉压(MAP)和舌下微循环各指标[包括:血管密度(TVD)、微血管血流指数(MFI)、异质性指数(HI)、灌注血管比例(PPV)、灌注血管密度(PVD)],并比较各组各指标的差异。结果:基线状态下各组各指标之间无统计学差异(P>0.05),休克时除Sham组外,各组各指标之间无统计学差异(P>0.05)。休克3h、6h时,SFI+NE组MAP较Model组、NE组、SFI组均有明显改善(P<0.05)。休克6h时,NE组、SFI组MAP较Model组升高(P<0.05)。休克1h时,TVD、MFI、HI、PPV、PVD各指标在NE组、SFI组和SFI+NE组间均无明显统计学差异(P>0.05),与Model组相比,SFI组和SFI+NE组TVD、SFI组和NE组PVD有明显改善(P<0.05)。休克3h时,TVD、MFI、PPV各指标SFI+NE组与NE组、SFI组相比无明显统计学差异(P>0.05),SFI组MFI、PVD指标较Model组有明显改善(P<0.05),SFI组PVD指标较NE组、SFI+NE组有明显改善(P<0.05)。休克6h时,SFI组MFI指标与Model组、NE组、SFI+NE组相比有明显改善(P<0.05)。其余各指标差异在各时间点各组间比较无统计学意义(P>0.05)。结论:参附注射液联合去甲肾上腺素相比于单独应用参附注射液或去甲肾上腺素可明显改善脓毒症休克兔的MAP,但对TVD、MFI、HI、PPV和PVD微循环指标的改善作用,与单独用药疗效相当。

Eeffects of Shenfu Injection Combined with Norepinephrine on Sublingual Microcirculation in Septic Shock Rabbits

Objective:To observe the effects of Shenfu injection combined with norepinephrine on sublingual microcirculation in septic shock rabbits.Method:Thirty New Zealand rabbits were randomized into 5 groups averagely.They were sham operation group(Sham group),model group(Model group),norepinephrine group(NE group),Shenfu injection group(SFI group)and Shenfu injection combined with norepinephrine group(SFI+NE group).Animals except those in Sham group were injected with lipopolysaccharide(LPS 2mg/kg)into the rabbit's ear vein to establish septic shock model.After model was successfully set up,each rabbit was administrated with the sodium lactate Ringer injection 30ml/kg for one hour.After the establishment of the model,the NE group and SFI+NE group were given noradrenalin(40μg/ml)by microinjection pump at the speed of 2.0μg/kg.min for 6 hours.The Model group and the SFI group were given an equal volume normal saline by microinjection pump for 6 hours too.Animals in SFI group and SFI+NE group were given Shenfu injection(2.5ml/kg)before injection of lipopolysaccharide(LPS),onset of shock,one hour after shock and two hours after shock,respectively.The mean arterial pressure(MAP)and sublingual microcirculation parameters were collected by power lab electrophysiological recorder and microsee sublingual microcirculation imaging system before the replication of septic shock model,onset of shock,1h,3h and 6h after shock.Results:There was no statistical difference among groups at baseline(P>0.05)when shock,there was also no statistical difference among groups for each index except for Sham group(P>0.05).At 3 and 6 hours after shock,MAP in SFI+NE group was significantly than that in Model group,NE group and SFI group(P<0.05).At 6 hours after shock,MAP in NE group and SFI group was higher than that in Model group(P<0.05).For the indexes of total vessel density(TVD),microvascular flow index(MFI),heterogeneity index(HI),proportion of perfused vessels(PPV),perfused vessel density(PVD),there was no significant statistical difference(P>0.05)at 1 hour after shock in the SFI+NE group compared with the NE group and SFI group,respectively.Compared with the Model group,TVD indexes in SFI group and SFI+NE group were significantly improved(P<0.05).There was no significant difference in the indexes of TVD,MFI,PPV among the SFI+NE group,SFI+NE group and the NE group at 3 hours after shock(P<0.05).The MFI and PVD indexes of the SFI group were significantly improved compared with the Model group(P<0.05).PVD index in SFI group was significantly improved compared with that in Model group,NE group and in SFI+NE group(P<0.05).Compared with that in Model group,NE group and SFI+NE group,MFI index in SFI group was significantly improved at 6 hours after shock(P<0.05).There was no significant difference in the other indexes among the groups at each time point(P>0.05).Conclusion:Shenfu injection combined with norepinephrine could significantly improve the mean arterial pressure of septic shock rabbits with septic shock compared with these two drugs used alone,but this combination showed similar effect on TVD,MFI,HI,PPV and PVD compared with Shenfu injection or norepinephrine used separately.