右美托咪定通过抑制NF-κB及炎症因子减轻失血性休克大鼠急性肺损伤

Dexmedetomidine attenuates acute lung injury in rats with hemorrhagic shock by inhibiting the NF-κb and inflammatory factors

目的探讨右美托咪定对失血性休克大鼠肺组织核因子κB(NF-κB)和炎症因子水平的影响及减轻急性肺损伤(ALI)的作用。方法将72只SD大鼠采用随机数字表法分为对照组(Con组,假手术)、ALI模型组(ALI组)、小剂量右美托咪定组(Dex-0.5组,0.5μg/kg)、中剂量右美托咪定组(Dex-1.5组,1.5μg/kg)、大剂量右美托咪定组(Dex-4.5组,4.5μg/kg)和NF-κB特异性抑制剂组(PDTC组),每组12只。经股动脉放血和股静脉回输血液,维持平均动脉压在35~45 mm Hg水平1 h,建立失血性休克ALI大鼠模型。建模后6 h采集股动脉血进行血气分析,计算氧合指数;处死大鼠取右肺组织测量湿/干重比(W/D),光镜观察并进行肺组织损伤评分,采用免疫组织化学法观察肺组织NF-κB表达水平;取左肺支气管肺泡灌洗液采用酶联免疫吸附试验检测白细胞介素(IL)-6、IL-10和肿瘤坏死因子-α(TNF)-α水平。结果与Con组比较,ALI组、Dex-0.5组大鼠W/D、肺组织损伤评分均升高,ALI组大鼠NF-κB、IL-6、IL-10、TNF-α水平均升高,差异均有统计学意义(P<0.05)。与ALI组比较,Dex-1.5组、Dex-4.5组、PDTC组大鼠W/D、肺组织损伤评分均降低,Dex-1.5组、Dex-4.5组大鼠NF-κB、IL-6、IL-10、TNF-α水平均降低,差异均有统计学意义(P<0.05)。与PDTC组比较,Dex-0.5组大鼠W/D升高,Dex-1.5组、Dex-4.5组大鼠NF-κB、IL-10、TNF-α水平均升高,差异均有统计学意义(P<0.05)。结论中、大剂量右美托咪定预处理可能通过抑制NF-κB活化及炎症因子表达减轻失血性休克大鼠ALI。

Objective To investigate the effects of dexmedetomidine on nuclear factor kappa-B(NF-κB)and inflammatory factors in lungs of rats with hemorrhagic shock and the alleviation of acute lung injury(ALI).Methods A total of 72 healthy SD rats were randomly divided into control group(Con group,sham operation),ALI model group(ALI group),small dose dexmedetomidine group(Dex-0.5 group,0.5μg/kg),medium dose dexmedetomidine group(Dex-1.5 group,1.5μg/kg),a large dose of dexmedetomidine group(Dex-4.5 group,4.5μg/kg)and a specific inhibitor of NF-κB group(PDTC group),12 rats in each group.Mean arterial pressure was maintained at 35-45 mm Hg for 1 h via femoral artery bloodletting and femoral vein re-infusion,and established rat model of ALI caused by hemorrhagic shock.Six h after modeling,femoral artery blood samples were collected for blood gas analysis to calculate oxygenation index,rats were sacrificed,right lungs were collected to measure the wet/dry weight ratio(W/D)and scored the lung tissue injury by light microscope observation,immunohistochemical method was used to measure the expression of NF-κB in lungs,left lungs bronchoalveolar lavage fluid was taken to measure the levels of interleukin(IL)-6,IL-10 and tumor necrosis factor(TNF)-αvia enzyme-linked immunosorbent assay.Results Compared with Con group,W/D and lung injury scores of ALI group and Dex-0.5 group were increased,and the levels of NF-κB,IL-6,IL-10 and TNF-αin ALI group were increased,and the differences were statistically significant(P<0.05).Compared with ALI group,W/D and lung injury scores of Dex-1.5 group,Dex-4.5 group and PDTC group were decreased,and the levels of NF-κB,IL-6,IL-10 and TNF-αin Dex-4.5 group were decreased,and the differences were statistically significant(P<0.05).Compared with PDTC group,W/D of Dex-0.5 group was increased,and the levels of NF-κB,IL-6,IL-10 and TNF-αin Dex-1.5 group,Dex-4.5 group were increased,and the differences were statistically significant(P<0.05).Conclusion Pretreatment with medium and high dosage of dexmedetomidine may alleviate AIL in rats with hemorrhagic shock via inhibiting the activation of NF-κB and the expression of inflammatory cytokines.