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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 protective effect of TLCK on lung injury induced by acute hemorrhagic necrotizing pancreatitis (AH-NP) in rats. Methods The SD rats were randomly divided into 7 groups with 10 rats in each group: ① normal control group injected with saline; ② control group injected with AHNP intravenously; ③ 5 μg / kg TLCK intervention with AHNP group; ④ group was 10μg / kg TLCK intervention group; ⑤ group was 20μg / kg TLCK intervention AHNP group. Group ¢ ô were given intravenous intervention immediately after the AHNP model was made; ⑥ group was treated with TLCK 30 min before the AHNP model; ¢ TLC group was treated with TLCK for 30 min after the AHNP model was established kg dose). The above 7 groups of animals were tested for the survival rate of 7d, which was used to screen the optimal dosage time and dose of TLCK. AHNP model using retrograde pancreaticobiliary injection of 5% sodium taurocholate established. According to the screening results, the experimental animals were divided into sham operation control group (N group), AHNP group (P group) and TLCK intervention group (TLCK 10μg / kg intravenously immediately after AHNP model was made) (T group). 6 rats in each group. Animals in the latter three groups were sacrificed at 6 hours after operation, alveolar macrophages (AMs) were obtained by bronchoalveolar lavage and the protein levels in bronchoalveolar lavage fluid (BALF) were measured. The activation of NF-κB and AM secretion of TNFα Level. The changes of myeloperoxidase (MPO) in lung tissue were measured and histological examination was performed. Results ① The survival rates of 7d group were 100%, 0%, 70%, 100%, 80%, 0% and 90% respectively. The lung tissue of N group had lower MPO activity and lower protein content of BALF. P group and T group were significantly higher than those of N group (P <0.05), while T group was lower than P group (P <0.05). The activity of TNFα secreted by AM in P group was significantly higher than that in N group and T group (P <0.05), but also significantly lower in N group (P <0.05). NF-κB is not expressed in N group, P group is high expression, T group is low expression. Conclusion TLCK can inhibit the expression of NF-κB, reduce the secretion of inflammatory cytokines, significantly reduce the lung injury caused by AHNP. The optimal dose of TLCK intervention is 10μg / kg, the best time for the immediate administration after the occurrence of AHNP.