不同剂量右美托咪定对脓毒症大鼠微循环的影响

Effect of different doses of dexmedetomidine on microcirculation of rats with sepsis

目的探讨不同剂量右美托咪定对脓毒症大鼠微循环系统的影响。方法 48只Wistar大鼠按随机数字法分为盲肠结扎穿孔术(CLP)组、小剂量治疗组、中剂量治疗组和大剂量治疗组,每组12只。脓毒症模型采用CLP法进行制作,小、中、大剂量治疗组大鼠模型制作完成后,分别将右美托咪定以2.5μg·kg^(-1)·h(-1)、5μg·kg^(-1)·h(-1)和10μg·kg^(-1)·h(-1)的速度经尾静脉持续泵入。记录各组大鼠CLP术后1、3、5 h的平均动脉压和心率,以及CLP后3 h动脉血气包括p H值、二氧化碳分压、氧分压、细胞外液剩余碱、碳酸氢盐水平、总二氧化碳含量、氧饱和度及血乳酸水平,并计算24 h各组大鼠死亡情况。结果四组大鼠平均动脉压及心率水平比较,差异均有统计学意义(F=2.935、3.862,P=0.005、0.001)。与CLP组相比,小、中、大剂量治疗组大鼠的平均动脉压水平在术后1 h均显著降低(P均<0.05),但术后3、5 h比较差异均无统计学意义(P均>0.05);而心率则在术后3、5 h开始降低(P均<0.05)。CLP组大鼠术后3、5 h的平均动脉压较1 h均显著降低(P均<0.05),而小、中、大剂量治疗组大鼠术后3、5 h的心率均较同组1 h显著降低(P均<0.05),小、中剂量治疗组大鼠术后5 h的心率均较同组3 h显著降低(P均<0.05)。四组大鼠p H值[(7.27±0.07)、(7.17±0.08)、(7.12±0.07)、(7.13±0.07)]、二氧化碳分压[(38±8)、(72±21)、(77±24)、(83±16)mm Hg]、细胞外液剩余碱[(-9.7±3.9)、(-3.2±2.8)、(-4.7±3.4)、(-2.0±1.7)mmol/L]、碳酸氢盐水平[(17.4±3.3)、(25.0±2.7)、(24.7±4.2)、(27.1±1.7)mmol/L]、总二氧化碳含量[(18.6±3.7)、(27.1±2.8)、(26.9±4.9)、(29.6±2.1)mmol/L]、氧饱和度[(97.8±1.0)%、(97.2±1.5)%、(93.9±4.2)%、(94.4±4.0)%]及血乳酸水平[(94.45±4.01)、(0.63±0.66)、(0.63±0.43)、(0.45±0.38)mmol/L]比较,差异均有统计学意义(F=21.902、34.460、30.096、33.709、33.988、18.076、39.916,P均<0.05),而氧分压水平[(115±17)、(118±23)、(105±19)、(109±22)mm Hg]比较,差异无统计学意义(F=1.545,P>0.05)。小、中、大剂量治疗组大鼠p H值、二氧化碳分压、细胞外液剩余碱、碳酸氢盐、总二氧化碳含量及血乳酸水平与CLP组大鼠比较,差异均有统计学意义(P均<0.05),而氧饱和度方面比较,中、大剂量治疗组大鼠均较CLP组有所降低(P均<0.05)。此外,小剂量治疗组大鼠总二氧化碳含量、氧饱和度及中剂量治疗组大鼠细胞外液剩余碱与大剂量治疗组比较,差异均有统计学意义(P均<0.05)。四组大鼠死亡构成比(11/1、9/3、3/9、2/10)比较,差异有统计学意义(χ~2=17.658,P=0.001),且中、大剂量治疗组较CLP组和小剂量治疗组均显著降低(P均<0.008)。结论右美托咪定在CLP脓毒症大鼠中持续输注3 h内即明显改善微循环系统,使心率显著下降并维持平均动脉压稳定。随着右美托咪定输注剂量的增加,CLP脓毒症大鼠的生存情况明显得到改善。

Objective To evaluate the effects of dexmedetomidine at different doses on the early microcirculatory system in septic rats.Methods A total of 48 Wistar rats were randomly divided into the cecal ligation and puncture(CLP)group,small-dose treatment group,medium-dose treatment group and large-dose treatment group,12 rats in each group.The sepsis model was made by the CLP method,and dexmedetomidine was given respectively at the speed of 2.5μg·kg-1·h-1,5μg·kg-1·h-1 and 10μg·kg-1·h-1 to rats in small,medium and large-dose treatment groups through continuous tail vein pumping.The mean arterial pressure and heart rate at 1,3,5 h after CLP were recorded;arterial blood gas was measured at 3 h after CLP,including pH,partial pressure of carbon dioxide,partial pressure of oxygen,base excess in extracellular fluid,and levels of bicarbonate,total carbon dioxide,oxygen saturation and blood lactic acid;the death of rats in each group at 24 h was calculated.Results The heart rate and the level of mean arterial pressure in the four groups were significantly different(F=2.935,3.862;P=0.005,0.001).Compared with the CLP group,the mean arterial pressure of rats in small,medium and large-dose treatment groups decreased significantly at 1 h after operation(all P<0.05),but there were no significant differences among the three groups at 3 h and 5 h after operation(all P>0.05).However,the heart rate of rats in small,medium and large-dose treatment groups began to decrease at 3 h and 5 h after operation(all P<0.05).The mean arterial pressure in the CLP group at 3 h and 5 h after operation was significantly lower than that at 1 h(all P<0.05),while the heart rate of rats in the small,medium and large-dose treatment groups at 3 h and 5 h after operation was significantly lower than that at 1 h(all P<0.05).The heart rate at 5 h after operation in the small and medium-dose treatment groups was significantly lower than that at 3 h(all P<0.05).There were significant differences at the pH value[(7.27±0.07),(7.17±0.08),(7.12±0.07),(7.13±0.07)],partial pressure of carbon dioxide[(38±8),(72±21),(77±24),(83±16)mmHg],base excess in extracellular fluid[(-9.7±3.9),(-3.2±2.8),(-4.7±3.4),(-2.0±1.7)mmol/L],and levels of bicarbonate[(17.4±3.3),(25.0±2.7),(24.7±4.2),(27.1±1.7)mmol/L],total carbon dioxide[(18.6±3.7),(27.1±2.8),(26.9±4.9),(29.6±2.1)mmol/L],oxygen saturation[(97.8±1.0)%,(97.2±1.5)%,(93.9±4.2)%,(94.4±4.0)%]and blood lactic acid[(94.45±4.01),(0.63±0.66),(0.63±0.43),(0.45±0.38)mmol/L]in the four groups(F=21.902,34.460,30.096,33.709,33.988,18.076,39.916;all P<0.05).In the same time,there was no significant difference in partial pressure of oxygen[(115±17),(118±23),(105±19),(109±22)mmHg;F=1.545,P>0.05].Compared with those in the CLP group,the pH value,partial pressure of carbon dioxide,base excess in extracellular fluid,bicarbonate,total carbon dioxide and blood lactic acid of rats in the small,medium and large-dose treatment groups were significantly different(all P<0.05),and the oxygen saturation was significantly lower in the medium and large-dose treatment groups than in the CLP group(all P<0.05).In addition,compared with the large-dose treatment group,the total carbon dioxide content and oxygen saturation in the small-dose treatment group and base excess in extracellular fluid in the medium-dose treatment group were significantly different(all P<0.05).The proportional mortality indicator of the four groups(11/1,9/3,3/9,2/10)was statistically significantly different(χ2=17.658,P=0.001),and it was significantly lower in the medium and large-dose treatment groups than in the CLP and small-dose treatment groups(all P<0.008).Conclusions The continuous infusion of dexmedetomidine into CLP sepsis rats within 3 hours can significantly improve the microcirculatory system,decrease the heart rate and stabilize the mean arterial pressure.The survival of CLP sepsis rats can be obviously improved with the increased dose of dexmedetomidine.