氧化应激诱发肠道菌群失调对慢阻肺营养不良的影响及其防治

Patients with chronic obstructive pulmonary disease are more likely to develop malnutrition than healthy people, and the patient's body mass index is inversely associated with the prognosis.Nutritional supplements are not effective for all cases, therefore,it is improtant to explore the possible mechanism of chronic obstructive pulmonary disease.Our previous research found that the structure of the digestive tract of COPD rats changed, and the anti-oxidative treatment of hydrogen could reduce the destruction of digestive tract structure, suggesting that oxidative stress could lead to the structural change of the chronic obstructive pulmonary disease. The gut flora in COPD patients are dysfunctional and H2S, an anti-oxidant gas, can restore the disturbed gut flora. The reduction of H2S produced by the gut flora also leads to the destruction of the gut structure. The homeostasis of H2S-gut epithelium-gut flora protects the gut Structure, to maintain normal digestive function. we hypothesized that "Chronic obstructive pulmonary disease can cause intestinal structural changes not only through systemic inflammation and some other causes". It may also be related to "oxidative stress → change of intestinal flora → reduction of H2S → change of epithelial cells". In this study, we will further explore the relationship between oxidative stress and gut flora in COPD mice and their effects on the structure and function of the digestive tract, as well as the effects of inhaled hydrogen anti-oxidative therapy on the regulation of COPD pulmonary flora imbalance and its significance in the repair of digestive tract structure and function.

慢性阻塞性肺疾病患者较健康人群更易出现营养不良，且患者体重指数与预后呈负相关关系。临床上治疗营养不良的手段有限，主要原因是营养不良机制未明。我们前期研究工作发现“慢阻肺大鼠消化道结构发生改变，氢气抗氧化治疗可以减轻消化道结构破坏”。提示氧化应激可以导致慢阻肺消化道结构改变。慢阻肺患者存在肠道菌群失调，抗氧化气体H2S可恢复紊乱的肠道菌群，肠道菌群产生的H2S减少会导致肠道结构破坏，H2S-肠道上皮-肠道菌群保持动态平衡保护肠道结构，维持正常的肠道功能。故我们提出假说：慢阻肺不仅可以通过全身炎症等原因，引起肠道结构改变。其还可能与“氧化应激→肠道菌群改变→H2S产生减少→肠道结构改变”有关。本研究将在前期研究的基础上，进一步探讨慢阻肺小鼠模型氧化应激与肠道菌群的关系及其对消化道结构和功能的影响，以及吸入氢气抗氧化治疗对慢阻肺肠道菌群失调的调理作用及其对修复消化道结构和功能的意义。

慢性阻塞性肺疾病患者较健康人群更易出现营养不良，且患者体重指数与预后呈负相关关系。临床上治疗营养不良的手段有限，主要原因是营养不良机制未明。我们前期研究工作发现“慢阻肺大鼠消化道结构发生改变，氢气抗氧化治疗可以减轻消化道结构破坏”。提示氧化应激可以导致慢阻肺消化道结构改变。慢阻肺患者存在肠道菌群失调，抗氧化气体H2S可恢复紊乱的肠道菌群，肠道菌群产生的H2S减少会导致肠道结构破坏，H2S-肠道上皮-肠道菌群保持动态平衡保护肠道结构，维持正常的肠道功能。我们的动物实验结果发现长期烟草烟雾暴露可导致大鼠肺部出现慢性炎症、肺气肿和肺功能下降等COPD的肺部表现以及体质量降低的肺外表现,也引起肝脏、脾 脏、胃和小肠等与消化吸收功能有关的消化道炎症反应,我们推测COPD的营养不良与消化道炎症所致病理改变有关,为了改善COPD的营养状态,不但要提供合适的营养物质,更重要的是防治消化道的炎症反应；而临床试验研究则发现与健康人比较，COPD稳定期患者的肠道菌群存在特征性改变，复诊治疗患者与初诊未用药治疗患者间的差异无统计学意义；COPD稳定期患者的果糖和甘露糖代谢、萜类化合物生物合成、氨基酸合成和同源重组功能基因通路显著减少，提示能量代谢功能下降；吸入氢氧气治疗虽然未能改变慢阻肺患者的肠道菌群结构和机体代谢，但能够改善患者的呼吸困难症状，值得推广。