TLCK对急性出血坏死性胰腺炎大鼠肺损伤的影响  

The effect of TLCK on acute hemorrhagic necrotizing pancreatitis associated with lung injury

作　　者：程石[1] 史敬东[1] 宋茂民[1] 

机构地区：[1]首都医科大学附属北京天坛医院普通外科,北京100050

出　　处：《中国普通外科杂志》2008年第11期1097-1101,共5页China Journal of General Surgery

基　　金：北京市科委科技新星计划资助课题(H020821500190)

摘　　要：目的探讨盐酸-对甲苯磺酰-L-赖氨酸氯甲基甲酮(TLCK)对急性出血坏死性胰腺炎(AH-NP)肺损伤的保护作用。方法将SD大鼠随机分为7组,每组10只:①组为注射生理盐水的正常对照组;②组为生理盐水静脉注射的AHNP对照组;③组为5μg/kg TLCK干预AHNP组;④组为10μg/kgTLCK干预组;⑤组为20μg/kg TLCK干预AHNP组。②～⑤组均于AHNP模型制成后立即静脉给予干预药物;⑥组为制AHNP模型30min前TLCK干预组;⑦组为制AHNP模型30 min后TLCK干预组(后2组TLCK均以10μg/kg剂量给药)。上述7组动物检测7d生存率,用于筛选TLCK的最佳给药时间和剂量。AHNP模型采用逆行性胰胆管注射5%牛磺胆酸钠建立。根据筛选结果再将实验动物分为:假手术对照组(N组),AHNP组(P组),TLCK干预组(于AHNP模型制成后立即静脉给予TLCK 10μg/kg)(T组)。每组大鼠6只。后3组手术后6 h处死动物,行支气管肺泡灌洗获取肺泡巨噬细胞(AM),并测定支气管肺泡灌洗液(BALF)中蛋白含量;检测AM中NF-κB活化情况及AM分泌TNFα水平。测定肺组织髓过氧化物酶(MPO)的变化,并行组织学检查。结果①～⑦组7d生存率分别为100%,0%,70%,100%,80%,0%和90%。N组肺组织MPO活性较低,BALF蛋白含量亦低;P组和T组显著高于N组(P<0.05),而T组显著低于P组(P<0.05)。N组AM可检测到低水平TNFα活性,P组AM分泌TNFα活性明显高于N组及T组(P<0.05)N组亦显著低于T组(P<0.05)。NF-κB在N组不表达,P组高表达,T组低表达。结论TLCK可通过抑制NF-κB表达,减少炎症细胞因子的分泌,明显减轻AHNP所致肺损伤。TLCK干预的最佳剂量为10μg/kg,最佳时间为AHNP发生后即时给药。Objective To investigate the effect of TLCK （N-alpha-tosyl-L-lysyl-chloromethylketone） on acute hemorrhagic necrotizing pancreatitis （AHNP） associated with lung injury. Methods Seventy SD rats were randomized into seven groups （ n = 10 in each group） ： groupl , normal control group （ rats were treated with 0.9% sodium chloride i. v. ） ; group 2, AHNP control group （ AHNP rats were treated with 0. 9% sodium chloride i. v. ） ; group 3 , AHNP rats were treated with 5 μg/kg TLCK ; group 4, AHNP rats were treated with 10 μg/kg TLCK; group5 , AHNP rats were treated with 20 μg/kg TLCK ; Group3 , 4,5were treated with TLCK i. v. immediately after the establishment of SAP rat model ; group 6, AHNP rats were treated with TLCK i. v. 30 minutes before the establishment of AHNP model ; group 7, AHNP rats were treated with TLCK i. v. 30 minutes after the establishment of AHNP rat model;Group 6,7 were treated with 10 μg/ kg TLCK. Group 1 - 7 were used to select the best dosage and administration time of TLCK by observing the survival rate for seven days. Then, according to the result of selecting, the SD rats were divided into three groups （n = 6 in each group ） ： group N, Sham operated control group （0.9 % sodium chloride was reversely injected into SD rat＇s pancreas and rats were treated with 0.9% sodium chloride i. v. ） ; group P ： AHNP group; group T： TLCK treatment group （AHNP rats were treated with 10 μg/kg TLCK immediately after the establishment of AHNP rat model）. The rats of the last three groups were killed 6 hours after operation. Alveolar macrophages （ AMs ） were harvested by bronchoalveolar lavage. The protein content of bronchoalveolar lavage fluids （ BALF ） , the myeloperoxidase （ MPO ） of lung tissue, and tumor necrosis factor α （ TNFα ） secreted by AMs were determined. The expression of NF-κB in AM was checked as well as lung histology. Results The survival rate of group 1 -7 was100% , 0%, 70%, 100%, 80%, 0%, and 90% respectively. The level of MP

关 键 词：胰腺炎 急性坏死性 肺损伤 NF-κB TLCK 肺泡巨噬细胞 

分 类 号：R657.5[医药卫生—外科学]