新近研究表明，饮食不节导致的肠源性内毒素血症（IETM），可上调TLR4介导的炎症通路，引发慢性低度炎症和胰岛素抵抗(IR)，促发多种代谢疾病。铁皮石斛是传统治疗“消渴症”要药，对糖尿病等多种代谢相关疾病均有良好的防治作用，机制与改善IR有关。前期研究证明，铁皮石斛能明显改善长期饮食不节模型大鼠呈现的糖脂紊乱、低度炎症，降低HOMA-IR。结合其“厚肠胃”功效及调节菌群、保护黏膜等作用，我们认为铁皮石斛改善饮食不节所致IR可能与调节肠道稳态，改善或阻断IETM介导的炎症反应有关。拟采用高糖高脂致胰岛素抵抗大鼠模型和Caco-2细胞模型，运用现代药理学方法及分子生物学技术，考察铁皮石斛对IETM、LPS/TLR4信号途径的影响，分析与IR相关性；并从IETM形成的三个关键环节阐明其作用机制。本研究可为铁皮石斛改善慢性代谢性疾病的机制研究提供新的切入点，并丰富石斛“厚肠胃”的现代科学内涵。

Recent studies have suggested that systemic, low level elevations of gut derived endotoxin (lipopolysaccharide, LPS) may play an important role in metabolic perturbations. As a triggering factor, LPS initiates a well-characterized signaling cascade that elicits many pro- and anti-inflammatory pathways when bound to its receptor, Toll-Like Receptor 4 (TLR4). Intestinal endotoxemia (IETM) and this stateis associated with a heightened pro-inflammatory and insulin resistance(IR). Dendrobium officinale as a traditional herb medicine mainly used for diabetes showed obvious protective effect in various metabolic diseases. Our previous studies have shown that it has obvious effect on the hyperglycemia ,hyperlipidemia, and can alleviate inflammation and insulin resistance in the rats with metabolic syndrome induced by a high sucrose and high fat diet(HSHF).Meanwhile it has obvious enterogastric function, such as modulating of enteric dysbacteriosis, improving gut barrier, promoting digestion, regulating intestinal immune, etc. We speculate that Dendrobium officinale improve HSHF diet induced metabolic disturbances and insulin resistance mainly depend on the regulation of intestinal homeostasis, improving or blocking the IETM mediated inflammatory reaction. In this regard, we first investigated whether Dendrobium officinale suppresses IETM, inflammation in HSHF diet induced metabolic syndrome model rats and analyze its correlation with markers of IR by dynamic observation of intestinal permeability, serum LPS concentration, pro- inflammatory factor and HOMA-IR. Furthermore, underlying mechanisms by which Dendrobium officinale may recover them will be further confirmed by Caco-2 cell models in vitro. This study aim to indicate that Dendrobium officinale prevents a high sucrose and high fat diet-induced insulin resistance and inflammation in rats through inhibition of IETM and its underlying mechanism. Our research will promote its application in the prevention and treatment of metabolic diseases especially induced by improper diet composition and it’s a new enrichment of enterogastric function.