不同剂量右美托咪定对脓毒症大鼠早期免疫调节的影响

目的通过对盲肠结扎穿孔（CLP）后的大鼠输注不同剂量右美托咪定来评估其免疫调节作用。方法48只盲肠结扎穿孔（CLP）后的 Wistar 大鼠随机（随机数字法）分为四组：（1）盲肠结扎穿孔组（CLP 组）；（2）2.5μg／（kg·h）右美托咪定治疗组（DEX2.5组）；（3）5μg／（kg·h）右美托咪定治疗组（DEX5.0组）；（4）10μg／（kg·h）右美托咪定治疗组（DEX10.0组）。监测 CLP 术后1 h、3 h 及5 h 的 HLA-DR 及细胞因子：IL-4、IL-6、IL-10及 TNF-α变化，同时监测平均动脉压（MAP）、心率（HR），并计算24 h 病死率。结果右美托咪定治疗组（包括DEX2.5组，DEX5.0组，DEX10.0组），各组间在 HLA-DR 水平、炎性介质水平、平均动脉压（MAP）及心率（HR）均无明显变化。与 CLP 组比较，右美托咪定治疗组（包括 DEX2.5组， DEX5.0组，DEX10.0组）的 HLA-DR 水平降低（P ＝0.020），促炎介质 IL-6水平在 CLP 术后3 h时明显增加（P ＝0.011），随后5 h 时下降，HR 明显下降（P ＜0.01）的同时 MAP 无明显变化（P ＝0.124）。与 CLP 组比较，右美托咪定治疗组的病死率的显著减少，且与剂量成正相关；CLP组，DEX2.5组，DEX5.0组，DEX10.0组病死率分别为91.7％，66.7％，25.0％和18.0％。结论右美托咪定在 CLP 脓毒症大鼠中持续输注5 h 内即开始诱导免疫调节，输注同时使 HR 显著下降并维持 MAP 稳定。随着右美托咪定输注剂量的增加，CLP 脓毒症大鼠的生存率显著改善。

Dose-related effects of dexmedetomidine on immunomodulation and mortality to septic shock in rats

Objective To study the immunomodulation effects of different dosage of dexmedetomidine (Dex)in the septic shock model of rats after cecal ligation and puncture (CLP).Methods After CLP, 48 wistar rats were randomly (random number)allocated in four groups:(1)CLP group;(2)small-dose Dex group 2.5 μg/(kg·h)];(3)medium-dose Dex group 5.0 μg/(kg·h)];(4) large-dose Dex group 10.0 μg/(kg·h)].HLA-DR (human leukocyte antigen-DR)and plasma cytokine (IL-4, IL-6,IL-10 and TNF-α)were measured,meanwhile mean arterial blood pressure (MAP),heart rate (HR)and mortality were also documented at 1,3,and 5 h after the CLP procedure.Results There were no obvious differences in HLA -DR level,levels of inflammatory mediators,MAP and HR among there Dex treatment groups.Compared with CLP group,HLA-DR level decreased in three Dex treatment groups (P =0.020)and pro-inflammatory mediator (IL-6)increased at 3 h (P =0.011 )then declined at 5 h with decreased HR (P <0.01),and without obvious change in MAP (P =0.124),and all of them led to a significantly decrease in the mortality.The mortalities in CLP group,small dose group,medium dose group and large dose group were 91.7%, 66.7%, 25.0% and 18.0%, respectively. Conclusions Dexmedetomidine used in rats with septic shock rats partially induced immunomodulation initiated within 5 h after CLP evidenced by decreased HR,maintenance of MAP and reduction of mortality rate in dose-dependent fashion.