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目的观察硫化氢(H2S)/胱硫醚-γ-裂解酶(CSE)在大承气汤抗脂多糖(LPS)所致老年大鼠急性肺损伤(ALI)过程中的变化。方法将88只SD老年大鼠随机分为假手术组、ALI模型组(经气管内滴注LPS复制ALI模型)、炔丙基甘氨酸(PPG,CSE抑制剂)组和大承气汤治疗组。分别于给药后4h、8h处死动物,测定肺系数;光镜观察肺组织形态学改变;化学法检测血浆H2S含量、肺组织丙二醛(MDA)含量、髓过氧化物酶(MPO)活性以及CSE活性的变化;RT-PCR方法检测肺组织CSEmRNA表达的变化。再将血浆H2S含量与上述指标进行相关性分析。结果气管内滴注LPS可引起肺组织明显的形态学改变;肺系数和肺组织MDA含量、MPO活性增加;血浆H2S含量、肺组织CSE活性及CSEmRNA表达下降。预先给予PPG可加重LPS所致肺损伤;而给予大承气汤后,肺组织损伤减轻,肺系数和肺组织MDA含量、MPO活性下降,血浆H2S含量、肺组织CSE活性及CSEmRNA表达增加。相关性分析显示,H2S含量与CSE活性呈正相关(r值=0.950～0.981,P均<0.01);与其他指标呈负相关(r值=-0.985～-0.933,P均<0.01)。结论H2S/CSE体系的下调参与了LPS所致老年大鼠ALI的发病;上调H2S/CSE体系是大承气汤抗LPS所致老年大鼠ALI的作用机制之一。
Objective To observe the changes of hydrogen sulfide (H2S)/cystathionine-γ-lyase (CSE) in the process of acute lung injury (ALI) induced by Dachengqi Decoction against lipopolysaccharide (LPS) in aged rats. Methods Eighty-eight elderly SD rats were randomly divided into sham-operated group, ALI model group (intratracheal instillation of LPS to replicate ALI model), propargylglycine (PPG, CSE inhibitor) group and Dachengqi Decoction treatment group. Animals were sacrificed at 4h and 8h after administration, and the lung coefficient was measured. Morphological changes of lung tissue were observed by light microscope; plasma H2S content, malondialdehyde (MDA) content, and myeloperoxidase (MPO) activity were measured by chemical method. And changes in CSE activity; RT-PCR method to detect changes in CSEmRNA expression in lung tissue. The plasma H2S content was then correlated with the above indicators. Results Intratracheal instillation of LPS could induce significant morphological changes in lung tissue; lung coefficient, lung tissue MDA content, MPO activity increased; plasma H2S content, lung CSE activity and CSE mRNA expression decreased. Pre-administration of PPG can aggravate LPS-induced lung injury. After administration of Dachengqi Decoction, lung tissue damage is reduced, lung coefficient and lung tissue MDA content, MPO activity are decreased, plasma H2S content, lung CSE activity and CSE mRNA expression are increased. Correlation analysis showed that H2S content was positively correlated with CSE activity (r = 0.950 to 0.981, P <0.01); it was negatively correlated with other indicators (r = -0.985 to -0.933, P <0.01). Conclusion The down-regulation of H2S/CSE is involved in the pathogenesis of ALI in aged rats induced by LPS. Upregulation of H2S/CSE is one of the mechanisms of Dachengqi Decoction in the treatment of ALI in aged rats induced by LPS.