右美托咪定可能通过抑制TLR4通路对LPS诱导的脓毒症小鼠急性肺损伤起保护作用

Dexmedetomidine may inhibit the TLR4 pathway play aprotective effect on the acute lung injury in sepsis mice induced by LPS

目的研究右美托咪定(Dex)对脂多糖(LPS)诱导的脓毒症(Sep)小鼠急性肺损伤(ALI)起保护作用的分子机制。方法将100只清洁级成年雄性BALB/c小鼠随机平均分为高浓度右美托咪定组(A组)、低浓度右美托咪定组(B组)、脓毒症组(C组)和空白对照组(D组)。A、B两组小鼠分别于建模前30min经腹腔注射Dex 12.5μg/kg和25μg/kg,A、B、C三组小鼠均用腹腔内注射LPS建立ALI模型,建模后0、12h用Western blot法检测各组小鼠肺组织中TLR-4水平,用酶联免疫吸附法(ELISA)检测各组小鼠肺组织中MyD88、NF-κB和IL-6水平,并检测肺组织湿/干质量比(W/D)。结果建模后,A、B、C三组小鼠肺组织中MyD88、NF-κB和IL-6水平均随时间延长而提高,且均显著高于D组(P<0.05)。各个时间点A、B、C三组MyD88、NF-κB和IL-6水平存在显著差异,C组显著高于A组(P<0.05),A组显著高于B组(P<0.05)。结论 TLR-4信号通路可能参与了脓毒症大鼠肺损伤过程,Dex可能通过抑制TLR-4通路来实现脓毒症大鼠的肺保护作用。

Objective Study on the molecular mechanism of protective effect of dexmedetomidine on acute lung inju- ry in sepsis mice induced by lipopolysaccharide. Methods Put randomly 100 clean grade adult male BALB/c mice into high concentrations of dexmedetomidine group （group A）,low concentrations of dexmedetomidine group （group B）, sepsis sepsis group （Group C） and blank control group （Group D）. A and B group of mice were injected DEX 12.5 mu g / kg and 25 g/kg before 30 min of modeling. A,B and C group of mice were intraperitoneal injection of LPS to estab- lish the model of ALL Detecting the level of TLR-4 in lung tissue of mice with Western blot after modeling 0 and 12 hours. Using enzyme linked immunosorbent method （ELISA） to detected MyD88, NF-κB and IL-6 levels in the lung tis- sue of the mice,and detection of lung tissue wet/dry weight ratio （W/D）. Results After modeling, level of MyD88, NF-κB and IL-6 in A,B and C group were increaseing with time, and were significantly higher than D group （P〈0.05）. Level of MyD88,NF- three groups of NF-κB in C group were significantly higher than that of group A （P〈0.05） ,and those in A group was significantly higher than that of group B （P〈0.05）. Conclusion TLR-4 signaling pathway may be involved in the process of lung injury in septic rats,Dex may inhibit the TLR-4 pathway to achieve lung protective effect in septic rats.