内源性硫化氢调节慢性阻塞性肺疾病大鼠氧化/抗氧化平衡

目的: 探讨硫化氢(H₂S)在吸烟(CS)联合脂多糖(LPS)建立的大鼠慢性阻塞性肺疾病(COPD)模型中的抗氧化作用。方法: 32只清洁级健康雄性SD (Sprague-Dawley)大鼠,随机分为4组:对照组(control)、CS+LPS组、CS+LPS+硫氢化钠(NaHS,H₂S供体)组、CS+LPS+炔丙基甘氨酸(PPG,胱硫醚-γ-裂解酶抑制剂)组。30 d后测定大鼠肺功能,光镜观察肺组织病理变化并予评分;测定血浆中H₂S含量及肺组织中胱硫醚-γ-裂解酶(CSE)蛋白表达;检测肺组织中丙二醛(MDA)含量、超氧化物歧化酶(SOD)及过氧化氢酶(CAT)活性以反映氧化应激。结果: 与对照组相比,CS+LPS组大鼠呼气峰流速(PEF)下降24%(P<0.01),气道内压(IP)升高66%(P<0.01),肺组织病理评分升高(P<0.01);NaHS或PPG干预后,与CS+LPS组比较,肺功能无改变;NaHS干预后,病理评分下降(P<0.05)。在第16 d时,CS+LPS组血浆中H₂S含量较对照组升高26%(P<0.05);30 d后,CS+LPS+PPG组较CS+LPS组H₂S含量降低22%(P<0.01)。CS+LPS组中CSE蛋白表达较对照组升高(P<0.01);与CS+LPS组比较,CS+LPS+NaHS组和CS+LPS+PPG组无显著差异。与对照组相比,CS+LPS组肺组织中MDA含量升高24%(P<0.05),总SOD活性升高47%(P<0.01),CAT活性升高52%(P<0.01);与CS+LPS组相比,NaHS干预后, MDA含量降低21%(P<0.05),总SOD活性及CAT活性无显著差异;而PPG干预后,总SOD活性下降33%(P<0.05)。结论: H₂S在COPD大鼠中起到抗氧化作用,CSE/H₂S途径可能参与COPD疾病的发展。

Endogenous hydrogen sulfide regulates oxidant/antioxidant balance in rat with chronic obstructive pulmonary disease

AIM: To investigate the role of hydrogen sulfide (H₂S) in the protection against oxidative stress in rats with chronic obstructive pulmonary disease (COPD).METHODS: The rat model of COPD was established by cigarette smoking (CS) combined with lipopolysaccharide (LPS) instillation. Thirty-two healthy male Sprague-Dawley rats were randomly divided into 4 groups: control group, CS+LPS group, CS+LPS+NaHS (H₂S donor) group and CS+LPS+PPG (DL-propargylglycine, an inhibitor of cystathionine-γ-lyase) group. After 30 days, the lung functions of the rats were measured, the histological changes of lungs were observed under light microscope and the pathological scores were calculated. The H₂S level in plasma and the protein expression of cystathionine-γ-lyase (CSE) in the lung tissues were measured. The content of malondialdehyde (MDA), the activity of superoxide dismutase (SOD) and catalase (CAT) were detected to reflect oxidative stress.RESULTS: Compared with control group, the peak expiratory flow (PEF) decreased by 24% and intra-pressure (IP) increased by 66% in CS+LPS group. The pathological scores of the lung tissues also increased. Compared with CS+LPS group, no change in the lung function was observed after given NaHS or PPG, but the pathological scores decreased in CS+ LPS+ NaHS group. Compared with control group, the content of H₂S in plasma was increased by 26% on day 16. Compared with CS+LPS group, the content of H₂S in plasma of CS+LPS+PPG group was decreased by 22% after 30 days. Compared with control group, the protein expression of CSE increased, and no statistical difference among CS+LPS group, CS+ LPS+ NaHS group and CS+LPS+PPG group was observed. Compared with control group, MDA content in the lung tissues was increased by 24% in CS+LPS group, the activity of SOD was increased by 47% and the activity of CAT was increased by 52%. Compared with CS+LPS group, the MDA content in CS+LPS+NaHS group was decreased by 21%, and no statistical difference in the activity of SOD and CAT was observed. The activity of SOD decreased by 33% after given PPG.CONCLUSION: H₂S plays a role as anti-oxidant in the rats with COPD. The CSE/ H₂S pathway may be involved in the development of COPD.