丁酸杆菌促进脂肪细胞凋亡参与肠道微生态介导肥胖OSAHS恶性循环的免疫防御和调控机制

Obesity and obstructive sleep apnea hypopnea syndrome (OSAHS) vicious circle has bidirectional relationship, there is still lack of effective treatment methods. Gut microbiome imbalance plays a key role in the process of obese-OSAHS circle, but the immune defense and regulation mechanism of gut microbiome steady-state is still unclear. Our preliminary work found that systemic inflammation related to proinflammatory and anti-inflammatory cytokines imbalance in obese children with OSAHS, and Clostridium butyricum has strong anti-inflammatory and antioxidant effect. Therefore, We will use the DGGE to analyze the different distribution of gut microbiome, detect proinflammatory and anti-inflammatory cytokines by ELISA, measure adipocytes apoptosis by TUNEL. This study aims to determine the immune defense and regulatory mechanism of Clostridium butyricum induced adipocytes apoptosis in gut microbiome mediated obese-OSAHS vicious circle through the whole clinical control test - adipocytes culture in vitro in vivo, to demonstrate the hypothesis that gut microbiome steady-state is an important endogenous defense mechanism of preventing and controling obese-OSAHS vicious circle, to elucidate the important significance of molecular immune and regulatory mechanism of through down-regulating TLR4 induced by Clostridium butyricum mediated adipocytes apoptosis, to break obese-OSAHS vicious circle and establish the theoretical basis for a new strategy for the prevention and control of obesity complications.

肥胖和阻塞性睡眠呼吸暂停低通气综合征（OSAHS）恶性循环具有双向相关，目前仍缺乏有效的治疗方法。肠道微生态菌群失衡在肥胖OSAHS恶性循环过程中起关键作用，但维持肠道菌群稳态的免疫防御和调控机制仍不清楚。我们前期工作发现肥胖OSAHS儿童存在系统性炎症与促炎抗炎因子失衡相关，并且丁酸杆菌具有较强的抗炎抗氧化作用。因此我们将用宏基因组学解析肠道菌群差异分布，ELISA检测促炎抗炎因子表达水平，TUNEL法测定脂肪细胞凋亡，通过整体临床对照-离体细胞培养方法，研究丁酸杆菌促进脂肪细胞凋亡参与肠道微生态介导肥胖OSAHS恶性循环的免疫防御调控机制，论证肠道菌群免疫稳态是防治肥胖OSAHS恶性循环的重要内源性防御机制的假说，对阐明丁酸杆菌通过下调TLR4介导脂肪细胞凋亡的分子免疫学调控机制有重要意义，为破解肥胖OSAHS恶性循环和防治肥胖并发症的新策略奠定理论基础。

我们前期研究发现肥胖OSAHS儿童存在系统性炎症与促炎抗炎因子免疫失衡，并且丁酸具有较强的抗炎抗氧化作用。提示肠道微生物组菌群失衡在肥胖OSAHS恶性循环过程中起关键作用，但维持肠道菌群稳态的免疫防御和调控机制仍不清楚。因此我们通过宏基因组学解析肠道菌群差异分布，ELISA检测促炎抗炎因子表达水平，TUNEL法测定脂肪细胞凋亡，通过整体临床对照-离体细胞培养等方法，研究丁酸促进脂肪细胞凋亡参与肠道微生态介导肥胖OSAHS恶性循环的免疫防御调控机制。研究结果发现：1)肥胖OSAHS患儿肠道微生物组菌群差异分布与促炎和抗炎因子失衡显著相关。其研究结果验证了肠道微生物组菌群及其免疫失衡是肥胖OSAHS恶性循环的重要原因。2)细菌脂多糖和丁酸通过TLR4介导促炎和抗炎因子表达在肥胖脂肪细胞增殖和凋亡中发挥重要作用。其研究结果明确了系统性炎症及抗炎因子IL-10和Treg免疫调节失衡在脂肪细胞增殖和凋亡中的作用。3)通过丁酸干预和TLR4/IL-10抗体阻断实验，揭示丁酸促进肥胖脂肪细胞凋亡部分是通过TLR4和IL-10表达促进肥胖脂肪细胞凋亡，从而参与OSAHS恶性循环的免疫防御机制。其研究成果已在国内外杂志发表论文9篇，会议壁报3篇，专利授权1项。本项目研究成果将为儿童肥胖OSAHS的防治提供新的策略和方法，因此具有较广阔的应用前景。

内容获取失败，请点击重试