右美托咪定预处理减轻脓毒症小鼠肝损伤的实验研究

Experimental Study of Dexmedetomidine Preconditioning to Alleviate Liver Injury in Mice with Sepsis

目的观察右美托咪定对脓毒症小鼠肝损伤的影响及其可能机制。方法24只健康的C57BL/6小鼠按随机数字表法分为3组(n=8):假手术(S)组、脓毒症模型(M)组和右美托咪定(D)组。S组仅打开腹腔翻动盲肠并不结扎盲肠,M组和D组采用盲肠结扎及穿孔术(CLP)建立脓毒症模型,D组在CLP术前30min腹腔注射右美托咪定100μg·kg-1,而S组和M组则注射相等容积的生理盐水。各组于术后12h取血标本,通过流式细胞仪检测Th17/Th22的表达情况;ELISA检测IL-6、IL-17和IL-22表达量;谷丙转氨酶(ALT)和谷草转氨酶(AST)应用试剂盒检测其表达水平。结果同S组对比,M组Th17细胞和Th22细胞表达频数及其分泌的IL-17与IL-22水平均显著升高,血清中IL-6、ALT与AST数值亦大幅上升(均P<0.001);与M组比较,D组外周血中Th17细胞和Th22细胞表达频数及其分泌的IL-17与IL-22水平均显著降低,血清中IL-6、ALT与AST分泌的量也明显下降(均P<0.01)。结论右美托咪定预处理能够有效减轻脓毒症小鼠肝损伤,这可能与其下调Th17/Th22细胞表达水平有关。

OBJECTIVE To observe the effect of dexmedetomidine on liver injury in sepsis mice and its possible mechanism.METHODS Twenty-four healthy C57 BL/6 mice were randomly divided into three groups(n=8):sham operation group(group S),sepsis model group(group M)and dexmedetomidine group(group D).In group S,only the abdominal cavity was turned over and the cecum was not ligated,and in group M and D,cecal ligation and perforation(CLP)was used to establish a sepsis model.Dexmedetomidine(100μg·kg-1)was slowly injected by intraperitoneal injection in group D about 30 min before CLP,while mice in group S and group M were injected with equal volume of normal saline.Taking blood by removing the eyeball at 12 h after operation.The expression of Th17/Th22 cells was detected by flow cytometry,the levels of IL-6,IL-17 and IL-22 were detected by ELISA,and the release levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were detected by the kit.RESULTS Compared with group S,the Th17 and Th22 cells were increased in group M,the expression levels of IL-6,IL-17,IL-22,ALT and AST were increased sharply(all P<0.001).Compared with group M,the frequency of Th17 and Th22 cells and the secretion of IL-6,IL-17,IL-22,ALT and AST were decreased in peripheral blood of group D(all P<0.01).CONCLUSION Dexmedetomidine may be involved in the repair of septic liver injury by down-regulating the secretion of inflammatory cytokine IL-17/IL-22 by Th17/Th22 cells.