L-精氨酸减轻重症急性胰腺炎肺损伤的机制研究

目的研究L-精氨酸（L-Arg）减轻急性出血坏死性胰腺炎（SAP）肺损伤的机制。方法采用逆行胰胆管注射牛磺胆酸钠（TAC）制造SAP模型，动物分为假手术组、SAP组、氯喹阻断组和L-Arg治疗组。计算肺组织学评分和肺损伤指数以评价肺损伤程度，荧光实时定量-PCR方法检测肺组织TLR2/4 mRNA表达变化。结果与假手术组（0.013±0.209E-2，0.110±0.742E-2）比较，SAP组肺组织TLR2和TLR4 mRNA表达明显增高（1.045±1.741E-2，2.067±1.914 E-2，P〈0.01），肺损伤加重，肺组织TNF-α浓度升高（P〈0.05或P〈0.01）；氯喹阻断TLR2/4 mRNA表达后（0.478±7.412E-2，0.012±1.513 E-3，P〈0.01），肺损伤程度减轻，肺组织TNF-α浓度降低（P〈0.05或P〈0.01）。给予L-Arg治疗后，TLR2/4 mRNA表达降低（0.260±0.891E-2，0.732±5.135 E-2，P〈0.01），肺损伤程度减轻，肺组织TNF-α浓度降低（P〈0.05或P〈0.01）。结论SAP时，肺组织内TLR2和TLR4表达上调。肺组织内TLR2和TLR4的表达增高可能在SAP肺损伤的发生、发展中起重要的作用。L-Arg可以通过抑制TLR2/4表达从而减轻肺损伤。

Mechanism of L-Arg relieving acute lung injury complicated in severe acute pancreatitis

Objective： To investigate the mechanism of L-Arg relieving acute lung injury complicated in severe acute pancreatitis （SAP）. Methods： Thirty-two Wistar male rats were randomly divided into the sham-operated group（ n = 8）, SAP group（ n = 8 ）, Chloroquine-inhibiteded group （ n = 8 ） and L-Arg treated group （ n = 8 ）. The lung was dissected for lung histological scores and bronchoalveolar lavage was harvested for lung injury index. TLR2/4mRNA expression in the lung was measured by RT-PCR. Results： TLR2/4 mRNA was detected in lung with low values in sthe ham-operated group （0. 013 ± 0. 209E-2, 0. 110 ± 0. 742E-2）, but they were markedly increased in SAP （ 1. 045 ± 1. 741E-2, 2. 067 ± 1. 914E-2, P 〈 0. 01 ）. Lung injury was aggravated, TNF-αconcentration in lung was increased （ P 〈 0. 05 or P 〈 0. 01 ）. Treatment with CQ effectively inhibited TLR2/4mRNA expression （ 0. 478 ± 7. 412E-2, 0. 012 ± 1. 513E-3, P 〈 0. 01 ）, TNF-αconcentration was decreased and lung injury was relieved（P 〈0. 05 or P 〈0. 01 ）. Treatment with L-Arg effectively inhibited TLR2/4mRNA expression（0. 260 ±0. 891E-2, 0. 732 ±5. 135 E-2, P 〈0. 01 ） and relieved lung injury, e TNF-α concentration was decreased. Conclusion： TLR2/4mRNA expression is increased in lungs in SAP. Up-regulation of TLR2/4 mRNA expression in lung may be involved in the genesis and the development of lung injury complicated in SAP. L-Arg can markly inhibit TLR2/4mRNA expression in lung in SAP, which leads to relief of lung injury.