不同浓度右美托咪定对脓毒症大鼠炎性因子、OCT和STAT3的影响及肝损伤保护机制

目的分析不同浓度的右美托咪定对脓毒症大鼠鸟氨酸氨基甲酰转移酶(OCT)、炎性因子和信号转导与转录因子3(STAT3)的影响及肝损伤保护机制。方法取50只雄性SD大鼠,随机分为假手术组(仅打开腹腔翻动盲肠)、模型组(经盲肠结扎穿孔术建立脓毒症大鼠模型)、低浓度组(脓毒症+右美托咪定2.50μg·kg-1·h-1)、中浓度组(脓毒症+右美托咪定5.00μg·kg-1·h-1)、高浓度组(脓毒症+右美托咪定10.00μg·kg-1·h-1),每组各10只。于造模后12 h,通过酶联免疫吸附试验法测定大鼠肝脏组织中炎性因子白细胞介素-6(IL-6)、白细胞介素-10(IL-10)和OCT的水平;用免疫印迹法测定肝脏组织中STAT3蛋白表达水平;经苏木精-伊红染色观察各组大鼠肝脏组织病理形态学改变。结果相比假手术组,模型组、低浓度组、中浓度组和高浓度组大鼠肝组织均出现不同程度的病理学损伤。模型组、低浓度组、中浓度组和高浓度组大鼠肝脏组织中OCT、IL-6、IL-10及STAT3的水平均显著高于假手术组(P<0.05);相比模型组,低浓度组、中浓度组和高浓度组OCT、IL-6、IL-10及STAT3的水平均显著降低(P<0.05);在低浓度组、中浓度组和高浓度组中高浓度组OCT、IL-6、IL-10及STAT3的水平最低,其次为中浓度组、低浓度组(P<0.05)。结论右美托咪定具有保护脓毒症大鼠肝损伤的作用,并具有剂量依赖性的特点,其作用机制可能与STAT3蛋白表达下调而参与右美托咪定保护脓毒症大鼠肝损伤的过程密切相关。

Effects of different concentrations of dexmedetomidine on organ protection related to anesthesia in sepsis rats

Objective To investigate the effects of dexmedetomidine at different concentrations on the protective mechanism of ornithine carbamyltransferase(OCT),inflammatory factors and STAT3 in sepsis rats.Methods Fifty male SD rats were randomly divided into sham operation group(open the cecum only),model group(establish sepsis rat model by cecal ligation and perforation),low concentration group(sepsis+dexmedetomidine 2.50μg·kg-1·h -1),medium concentration group(sepsis+dexmedetomidine 5.00 μg·kg--1·h -1),and high concentration group(sepsis+dexmedetomidine 10.00μg·kg-1·h -1),10 rats in each group.The levels of interleukin-6(IL-6),interleukin-10(IL-10) and OCT in rat liver tissues were measured by enzyme-linked immunosorbent assay 12 hours after modeling.The expression of STAT3 protein in liver tissues was measured by western blotting.The pathological changes of liver tissues were observed by hematoxylin-eosin staining.Morphological changes.Results Compared with sham-operated group,the liver tissues of model group,low concentration group,medium concentration group and high concentration group showed different degrees of pathological damage.The levels of OCT,IL-6,IL-10 and STAT3 in liver tissue of model group,low concentration group,medium concentration group and high concentration group were significantly higher than those of sham operation group(P <0.05).Compared with model group,the levels of OCT,IL-6,IL-10 and STAT3 in low concentration group,medium concentration group and high concentration group were significantly lower(P <0.05).The levels of OCT,IL-6,IL-10 and STAT3 were the lowest in the high concentration group,followed by the medium concentration group and the low concentration group(P <0.05).Conclusion Dexmedetomidine has a dose-dependent protective effect on liver injury in sepsis rats,suggesting that 2-adrenergic receptor has a dose-dependent effect,and its mechanism may be closely related to the down-regulation of STAT3 protein expression and participation in the process of dexmedetomidine protecting liver injury in sepsis rats.