大承气汤对老年大鼠急性肺损伤过程中H_2S/CSE的影响

Influences of Dachengqi Decoction on H_2S and CSE in course of lung lesion in aged rats

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） and cystathionine-γ-lyase （CSE） .in Dachnegqi the course of resisting acute lung lesion （ALL） induced by lipopolysaccharide （LPS） with Decoction in aged rats. Methods SD adult rats （n = 88 ） were randomly divided into the sham-operation group, ALL model group （established by intratracheal instillation of LPS to induce ALL）, propargylglycin （PPG, an inhibitor of CSE ） group and Dachengqi Decoction group. After medicine administration for 4 and 8 hours the rats were killed and the lung coefficients were determined respectively. The morphological changes in the lung tissue were observed with optical microscope, the plasma content of H2S and malondialdehyde （ MDA）, and the activities of myeloperoxidase （MPO） and CSE were detected by using chemical method. The changes of the expression of CSE-mRNA were detected by applying RT-PCR. The correlation between plasma H2S and the above indexes were morphological changes in the lung tissue were induced by the intratracheal instillation of LPS. The lung coefficients, content of MDA and activity of MPO were improved. The plasma content of H2S, CSE activity and CSE-mRNA expression decreased. The preadministration of PPG aggravated the lung lesion induced by LPS, and Dachengqi Decoction relieved the lung lesion, reduced lung coefficients, MDA content, and MPO activity, and at the same time increased the plasma content of H2S, CSE activity and CSE-mRNA expression. The outcomes of correlation analysis showed that H2S was correlated to CSE activity （ r =0. 950 - 0. 981, all P 〈 0.01 ）, and negatively related to other indexes （ r = - 0.985- - 0. 933, all P 〈 0.01 ）. Conclusion The down-regulation of H2S-CSE system takes part in the onset of ALL induced by LPS in aged rats. The up-regulation of H2S- CSE system is one of mechanisms of Dachengqi Decoction resisting ALL induced by LPS in aged rats.