摘要目的 评价右美托咪定对脓毒症大鼠肺损伤时高迁移率族蛋白B1(HMGB1)/Toll样受体(TLRs)信号通路的影响.方法 SPF级健康成年雄性Wistar大鼠24只,15～18周龄,体重200～250 g,采用随机数字表法分为3组(n=8):假手术组(S组)、脓毒症组(Sep组)和右美托咪定组(D组).D组腹腔注射右美托咪定25 μg/kg,S组和Sep组腹腔注射等容量生理盐水.Sep组和D组采用盲肠结扎穿孔法制备大鼠脓毒症模型.结扎后24h处死大鼠取右侧肺脏,光镜下观察病理学结果,进行肺损伤评分;采用ELISA法检测髓过氧化物酶(MPO)活性、IL-1β、IL-6及TNF-α含量;计算肺湿重/干重(W/D)比值,采用Western blot法检测HMGB1、TLR2和TLR4表达水平.结果 与S组比较,Sep组和D组肺组织MPO活性、肺损伤评分、W/D比值、IL-1β、IL-6、TNF-α含量、HMGB1、TLR2和TLR4表达水平升高(P＜0.05);与Sep组比较,D组肺组织MPO活性、肺损伤评分、W/D比值、IL-1β、IL-6、TNF-α含量、HMGB1、TLR2和TLR4表达水平降低(P＜0.05).结论 右美托咪定通过抑制HMGB 1/TLRs信号通路减轻脓毒症大鼠肺损伤.

abstractsObjective To evaluate the effect of dexmedetomidine on high-mobility group box 1 protein (HMGB1)/Toll-like receptors (TLRs) signaling pathway during lung injury in septic rats.Methods Twenty-four SPF healthy adult male Wistar rats,aged 15-18 weeks,weighing 200-250 g,were divided into 3 groups (n =8 each) using a random number table:sham operation group (group S),sepsis group (group Sep) and dexmedetomidine group (group D).Dexmedetomidine 25 μg/kg was intraperitoneally injected in D group,while the equal volume of normal saline was given instead in S and Sep groups.Sepsis was produced by cecal ligation and puncture in Sep and D groups.The rats were sacrificed at 24 h after operation,and the right lung was removed for examination of the pathological changes which were scored and for determination of myeloperoxidase (MPO) activity,content of interleukin-1β (IL-1β),IL-6 and tumor necrosis factor-α (TNF-α) in lung tissues (by enzyme-linked immunosorbent assay),wet to dry weight ratio (W/D ratio) and expression of HMGB1,TLR2 and TLR4 in lung tissues (by Western blot).Results Compared with group S,the MPO activity,lung injury score,W/D ratio,content of IL-1β,IL-6,TNF-α and expression of HMGB1,TLR2 and TLR4 were significantly increased in Sep and D groups (P＜0.05).Compared with group Sep,the MPO activity,lung injury score,W/D ratio,content of IL-1β,IL-6,TNF-α and expression of HMGB1,TLR2 and TLR4 were significantly decreased in group D (P＜0.05).Conclusion Dexmedetomidine reduces lung injury through inhibiting HMGB1/TLRs signaling pathway in septic rats.