利多卡因减轻脓毒症大鼠肺血管内皮功能障碍时对高迁移率族蛋白B1 mRNA表达的影响

Effect of lidocaine on expression of high mobility group box 1 protein mRNA during lidocaine-induced attenuation of pulmonary vascular endothelial dysfunction in septic rats

目的:评价利多卡因减轻脓毒症大鼠肺血管内皮功能障碍时对高迁移率族蛋白B1(HMGB1)mRNA表达的影响。方法:清洁级健康雄性SD大鼠30只,8~12周龄,体重250~300 g。采用随机数字表法将其分为3组(n=10):假手术组(S组)、脓毒症组(C组)和利多卡因组(L组)。采用盲肠结扎穿孔法制备脓毒症模型。S组只行手术,不结扎。L组大鼠模型制备后即刻尾静脉注射利多卡因10 mg/kg,后以10 mg·kg^(-1)·h^(-1)输注3 h,S组和C组输注等量生理盐水。于模型制备后24 h时麻醉后处死大鼠,采集下腔静脉血,取肺组织。采用ELISA法测定血清TNF-α和Syndecan-1浓度,实时荧光定量PCR法检测肺组织HMGB1 mRNA的表达,确定肺湿重/干重比值,透射电镜下观察肺血管内皮结构。结果:与S组比较,C组和L组血清TNF-α、Syndecan-1浓度和肺湿重/干重比值升高,肺组织HMGB1 mRNA表达上调(P<0.05);与C组比较,L组血清TNF-α、Syndecan-1浓度和肺湿重/干重比值降低,肺组织HMGB1 mRNA表达下调(P<0.05)。透射电镜下,S组大鼠肺血管内皮完整连续,结构致密;C组大鼠肺血管内皮不连续,结构明显疏松;L组大鼠肺血管内皮连续性基本完整,结构稍疏松。结论:利多卡因可能通过抑制HMGB1 mRNA表达,减轻脓毒症大鼠肺血管内皮功能障碍。

Objective To evaluate the effect of lidocaine on the expression of high-mobility group box 1 protein(HMGB1)mRNA during lidocaine-induced attenuation of pulmonary vascular endothelial dysfunction in septic rats.Methods Thirty clean-grade healthy male Sprague-Dawley rats,aged 8-12 weeks,weighing 250-300 g,were divided into 3 groups(n=10 each)by the random number table method:sham operation group(S group),sepsis group(C group)and lidocaine group(L group).Sepsis model was developed by cecal ligation and puncture in anesthetized animals.In group S,only surgery was performed without ligation.In group L,lidocaine 10 mg/kg was injected into the tail vein immediately after model preparation,followed by 10 mg·kg^(-1)·h^(-1) infusion for 3 h.Groups S and C received the equal volume of normal saline instead.At 24 h after model preparation,rats were sacrificed and blood samples were collected from the inferior vena cava,and lung tissues were harvested.Serum tumor necrosis factor-alpha(TNF-α)and syndecan-1 levels were measured by enzyme-linked immunosorbent assay,HMGB1 mRNA expression in lung tissues was detected using quantitative real-time polymerase chain reaction,wet/dry lung weight ratio was measured,and pulmonary vascular endothelial structure was observed with a transmission electron microscope.Results Compared with group S,the serum TNF-αand syndecan-1 concentrations and wet/dry lung weight ratio were significantly increased,and the expression of HMGB1 mRNA in lung tissues was up-regulated in C and L groups(P<0.05).Compared with group C,the serum TNF-αand syndecan-1 concentrations and wet/dry lung weight ratio were significantly decreased,and the expression of HMGB1 mRNA in lung tissues was down-regulated in group L(P<0.05).The results of transmission electron microscope showed that the pulmonary vascular endothelium was intact and continuous,and the structure was dense in group S;the pulmonary vascular endothelium was discontinuous,and the structure was significantly loose in group C;the pulmonary vascular endothelium was basically intact,and the structure was slightly loose in group L.Conclusions Lidocaine may reduce pulmonary vascular endothelial dysfunction in septic rats by inhibition of HMGB1 mRNA expression.