p38MAPK／iNOS／HO-1信号通路在赤芍减轻大鼠内毒素性急性肺损伤中的作用

Role of p38 mitogen activated protein kinase pathway in attenuation of LPS-induced acute lung injury by Radix Paeoniae Rubra in rats

目的 评价p38MAPK／iNOS／HO-1信号通路在赤芍减轻大鼠内毒素性急性肺损伤（Au）中的作用。方法健康清洁级雄性Wistar大鼠40只，随机分为5组（n=8）：生理盐水对照组（C组）、内毒素组（L组）、赤芍组（R组）、赤芍预处理组（PR组）和SB203580组（S组）。气管内滴注脂多糖（LPS）制备大鼠ALI模型。L组气管内滴注1ml LPS溶液（2．5mg／kg）；C组滴注等容量生理盐水；R组、PR组分别于气管内滴注LPS后、滴注前2h，经股静脉输注赤芍注射液15mg·k^-1·h^-12h；S组于气管内滴注LPS前3h，经股静脉输注SB203580溶液2．5μmol·kg^-1·h^-1 3h。于气管内滴注鹏后6h时，经颈动脉采血样2ml，行血气分析及测定血清NO浓度；颈动脉放血处死大鼠，测定支气管肺泡灌洗液蛋白浓度，计数中性粒细胞及细胞总数，检测肺组织MDA含量，p38MAPK、HO-1及iNOS的表达，观察肺组织病理学结果。结果与C组比较，其余各组肺组织p38MAPK、iNOS及HO-1表达上调，支气管肺泡灌洗液中性粒细胞计数比、蛋白浓度、肺组织MDA含量及血清NO浓度升高，PaO2和HCO3^-浓度降低（P〈0．01）；与L组比较，R组、PR组和S组p38MAPK及iNOS表达下调，HO-1表达上调，支气管肺泡灌洗液中性粒细胞计数比、蛋白浓度、肺组织MDA含量及血清NO浓度降低，PaO2和HCO3^-升高（P〈0．05）；R组、PR组和S组肺组织损伤程度较L组减轻。结论赤芍可减轻大鼠内毒索性急性肺损伤，可能与抑制p38MAPK／iNOS／HO-1信号通路有关。

Objective To investigate the role of p38 mitogen activated protein kinase （MAPK） /iNOS/ H O-1 in attenuation of LPS-induced acute lung injury（ALl） by Radix Paeoniae Rubra （RPR） in rats. Methods Forty pathogen-free male Wistar rats weighing 200-250 g were randomly divided into 5 groups （ n = 8 each） ： group Ⅰ control （C）; groupⅡ LPS; group Ⅲ RPR; group Ⅳ RPR precondtioning and groupV SB203580 （p38MAPK specific inhibitor）. ALl was induced by slow intra-tracheal instillation of LPS 2.5 mg/kg in 1ml of normal saline （NS） in group Ⅱ -Ⅴ . RPR 30 mg/kg was infused iv over 2 h simuhaneously with and at 2 h before intra-tracheal LPS instillation in group Ⅲ and Ⅳ respectively. In groupV SB203580 5 ptmol/kg was infused iv over 2 h at 3 h before intra-tracheal LPS instillation. Arterial blood samples were taken at 6 h after intra-tracheal LPS instillation for blood gas analysis and determination of serum NO concentration. The animals were sacrificed by exsanguination. The lungs were immediately removed for microscopic examination and determination of p38MAPK and HO-1 and iNOS expression and MDA content in the lung tissue. The left lung was lavaged and broncho- alveolar lavage fluid （BALF） was collected for determination of neutrophil count and protein concentration. Results LPS intra-tracheal instillation significantly decreased PaO2, PaCO2 and HCOf concentration and increased serum NO concentration, the number of neutrophils and protein concentration in BALF, and p38MAPK and iNOS and HO-1 expression and MDA content in the lung tissue. RPR and RPR preconditioning and SB203580 significantly attenuated the LPS-induced changes in group m , 1w andV as compared with group 1I . The LPS intratracheal instillation induced pathologic changes of the lung were also attenuated in group Ⅲ, Ⅳ and Ⅴ . Conclusion RPR can attenuate LPS-induced ALI through p38MAPK/iNOS/HO-1 signalling pathway.