从肠淋巴液物质基础探讨"肺病治肠"在重症胰腺炎急性肺损伤治疗中的应用

Acute lung injury is the important factor that causes the high mortality of severe acute pancreatitis , which can be cured by the improved gut barrier function treated by traditional Chinese medicine with the principle of Unblocking The Bowels To Purge. While the mechanism of "Treating The Intestines To Relieve Lung Disorder" is unclear. The research put forward a hypothesis that "the way of the mesenteric lymph is the critical way of 'Treating The Pulmonary Disease Through Treating The Intestine' '' and the hypothesis that "the cytokines represented as HMGB1 and its receptor RAGE is the material basis when the severe acute pancreaitis causing acute lung injury through mesenteric lymph",which based on the research basis that is the ligation of mesenteric lypmph can relieve the acute lung injury of the rats with severe acute pancreatitis , and also based on the anatomy and physiological characteristic of mesenteric lymph .Try to explain the mechanism of Da Cheng Qi Decoction's alleviating the lung injury from the level of gene，protein and the morphology by observing the improvement of the gut barrier function ,the change of the endotoxin in the blood serum and mesenteric lymph, the influence of the cytokine such as HMGB1 and its receptor RAGE. That is Da Cheng Qi Decoction's alleviating the lung injury, which is achieved by the improved gut barrier function and then the less cytokine in the mesenteric lymph acting on the lung, which provide a new idea for investigating the modern medical mechanism for the traditional Chinese medical theory "Treating The Intestines To Relieve Lung Disorder".

重症胰腺炎急性肺损伤是重症胰腺炎高死亡率的重要原因，是目前临床治疗的难点和热点。通腑泻下中药大承气汤通过治"肠"能有效改善"肺"损伤，但中医"肺病治肠"的现代医学机理尚不明确。本研究基于前期对肠淋巴结扎后减轻重症胰腺炎大鼠急性肺损伤的研究基础、肠淋巴解剖结构和生理功能特点提出"肠淋巴途径可能为重症胰腺炎大鼠'肺肠相关'的关键途径"及"以HMGB1及其受体RAGE为代表的炎症因子为肠淋巴液介导重症胰腺炎大鼠急性肺损伤的物质基础"。拟通过大承气汤干预后，观测肠屏障功能改善、血和肠淋巴液中内毒素、HMGB1及其受体RAGE等炎症因子的变化、肺损伤的减轻，试从基因、蛋白、组织形态学等水平讨论大承气汤治疗重症胰腺炎急性肺损伤的机制。即大承气汤可能通过改善重症胰腺炎大鼠的肠屏障功能，从而减轻其肠淋巴液中炎症因子的介导，进而减轻急性肺损伤，为探究中医理论"肺病治肠"的现代医学机理提供新思路。

项目背景：重症急性胰腺炎急性肺损伤可以通过通腑泻下法得到治疗作用，实践了“肺病治肠”的中医理论，但其机理不明。.研究内容：本项目组从“肠淋巴途径”探讨中医理论“肺病治肠”的实质及物质基础，拟通过大承气汤干预重症急性胰腺炎大鼠急性肺损伤，观测肠屏障功能改善、血和肠淋巴中炎症因子的变化、肺损伤的减轻，试从基因、蛋白、组织形态学等水平讨论大承气汤治疗重症胰腺炎急性肺损伤的机制。.关键数据：.（1）胰腺组织病理损伤：经过肠淋巴结扎及大承气汤干预后，胰腺组织的病理损伤明显减轻。.（2）肠屏障功能：经过肠淋巴结扎及大承气汤干预后肠屏障功能明显改善。（从以下几个方面体现：小肠病理损伤、免疫组化、透射电镜、血清DAO、血清D-乳酸）.（3）肠淋巴炎症因子变化：经过肠淋巴结扎及大承气汤干预后，肠淋巴炎症因子明显降低。（肠淋巴荧光定量PCR）.（4）肺损伤变化：经过肠淋巴结扎及大承气汤干预后，肺损伤明显减轻。（从以下几个方面体现：病理损伤，MPO，荧光定量PCR,Western Blot,免疫组化）.（5）全身炎症反应：经过肠淋巴结扎及大承气汤干预后，血清炎症因子明显降低。.重要结果：.（1）从基因、蛋白、组织形态学等角度阐释重症胰腺炎大鼠急性肺损伤可通过大承气汤的推陈致新、荡涤肠胃的方法来改善肠屏障功能，从而减少肠淋巴液中炎症因子的介导而实现。.（2）肠淋巴途径为重症胰腺炎大鼠“肺肠相关”的关键途径；以HMGB1及其受体RAGE为代表的炎症因子为肠淋巴液介导重症胰腺炎大鼠急性肺损伤的物质基础。.科学意义：.（1）为“通腑泻下法”治疗重症急性胰腺炎急性肺损伤的作用机理提供新思路。(2)阐释“肠淋巴途径”为重症急性胰腺炎急性肺损伤的重要中间环节。.(3)为内科治疗及外科治疗重症急性胰腺炎急性肺损伤提供理论依据。