盐酸戊乙奎醚对脓毒症致大鼠急性肺损伤时Toll样受体4及NF-κB表达的影响  

Effects of penehyclidine hydrochloride on expression of Toll like receptor-4 and nuclear factor kappa B in a rat model of sepsis-induced acute lung injury

作　　者：付朝晖[1] 姚尚龙[1] 袁世荧[1] 

机构地区：[1]430022武汉市,华中科技大学同济医学院附属协和医院麻醉科

出　　处：《中华麻醉学杂志》2013年第9期1134-1137,共4页Chinese Journal of Anesthesiology

摘　　要：目的 评价盐酸戊乙奎醚对脓毒症致大鼠急性肺损伤时Toll样受体4（TLR4）及NF-κB表达的影响.方法 健康成年雄性SD大鼠72只,体重180～220 g,采用随机数字表法分为3组（n=24）：假手术组（S组）、脓毒症致急性肺损伤组（ALI组）和盐酸戊乙奎醚组（PHC组）.采用盲肠结扎穿孔法制备脓毒症致大鼠急性肺损伤模型,PHC组于结扎后即刻肌肉注射盐酸戊乙奎醚0.45 mg/kg.于结扎后6、12、24和36 h时采用ELISA法测定肺泡灌洗液TNF-α和IL-6的浓度；RT-PCR及Western blot法检测肺组织TLR4的表达,Western blot法检测NF-κBp65的表达；光镜下观察肺组织病理学结果并进行评分,计算肺组织湿干重比（W/D比）,检测肺组织髓过氧化物酶（MPO）活性.结果 与S组比较,ALI组结扎后6、12和24 h时肺泡灌洗液IL-6浓度、结扎后6和12 h时肺泡灌洗液TNF-α浓度、各时点肺组织TLR4和NF-κB p65表达水平、病理学评分、W/D比及MPO活性升高（P＜0.05）；与ALI组比较,PHC组结扎后6和12 h时肺泡灌洗液TNF-α浓度、各时点肺泡灌洗液IL-6浓度、肺组织TLR4和NF-κBp65表达水平、病理学评分、W/D比及MPO活性降低（P＜0.05）.结论 盐酸戊乙奎醚通过阻断肺组织TLR4表达,抑制NF-κB活化,降低炎性反应,从而减轻脓毒症致大鼠急性肺损伤.Objective To evaluate the effects of penehyclidine hydrochloride （PHC） on the expression of Toll like receptor-4 （TLR4） and nuclear factor kappa B （NF-κcB） in a rat model of sepsis-induced acute lung injury （ALI）.Methods Seventy-two adult male Sprague-Dawley rats,weighing 180-220 g,were randomly divided into 3 groups （n =24 each） using a random number table：shame operation group （group S）,ALI group and PHC group.Sepsis-induced ALl was induced by cecal ligation and puncture in anesthetized rats.In group PHC,PHC 0.45 mg/kg was intramuscularly injected immediately after cecal ligation and puncture.At 6,12,24 and 36 h after ligation,the broncho-alveolar lavage fluid （BALF） was collected for detection of TNF-α and IL-6 concentrations and the lungs were removed for determination of the expression of TLR4 （using RT-PCR and Western blot） and NF-κBp65 （using Western blot） in lung tissues and for microscopic examination.The pathological changes of lungs were scored.The wet to dry lung weight （W/D） ratio was calculated and the activity of myeloperoxidase （MPO） in lung tissues was measured.Results As compared with S group,the IL-6 concentrations in BALF at 6,12 and 24 h after ligation,TNF-α concentration in BALF at 6 and 12 h after ligation,and the expression of TLR4 and NF-κBp65,pathological scores,W/D ratio and MPO activity at each time point were significantly increased in ALI group （P 〈 0.05）.Compared with ALI group,the TNF-α concentration in BALF at 6 and 12 h after ligation,and IL-6 concentrations in BALF,the expression of TLR4 and NF-κBp65,pathological scores,W/D ratio and MPO activity at each time point were significantly decreased in group PHC （P 〈 0.05）.Conclusion PHC inhibits NF-κB activation and decreases inflammatory responses through blocking TLR4 expression in lung tissues,thus attenuating sepsis-induced ALI in rats.

关 键 词：胆碱能拮抗剂 脓毒症 呼吸窘迫综合征 成人 TOLL样受体4 NF-ΚB 

分 类 号：R459.7[医药卫生—急诊医学]