紧密连接蛋白（Tight Junction，TJ）是目前黏膜屏障的研究热点，是细胞与细胞间最为重要的连接方式，它可选择性的区分小分子，以及细菌、病毒等外来侵入性大分子，在肠道屏障的维护中起着举足轻重的作用。而这一作用，与中医"正气"的概念极为接近。以往对补益药的研究多为直接对某种病理模型的改善，很少能区分出机体本身的"正气"，以及补益药所谓"补"和"益"的作用。.本研究试图构建由补益药、机体屏障及外来邪毒组成的研究体系，以屏障功能代表"正气"；以细菌感染代表"外邪"； 采用整体动物模型与体外细胞培养相结合的方式，通过对上皮细胞形态及行为、细菌侵袭力及细胞通透性考察、紧密连接结构破坏、炎症介质释放以及TNF-α/NF-kB/MLCK信号转导的调控等角度研究在细菌侵入之时，机体屏障功能的变化，以及补益药四君子汤所可能发挥的顾护、治疗及补益作用，为"正气存内，邪不可干"提供实验依据。

Mucosal barrier is the most important barrier in the intestine. It constitutes with integrity of the intestinal epithelial cells(IEC) and the junction between adjacent intestinal epithelial cells with the function of regulate transepithelial water and solute transport(such as simple sugars, amino acids, nucleotides, vitamins and hormones, etc.).There are several kinds of connection between adjacent epithelial cells, such as tight junction(TJ), and gap junction(GJ), adherence junction(AJ), and desmosome and others. TJ is most important connections in the epithelial cell, its function is to allow ions and small molecules soluble substances through while block toxic marcomolecules and microorganisms. This particular physiological function plays an important role in the maintenance of the intestinal barriers. A significant body of evidence has demonstrated that intestinal barrier defects are involved in several intestinal and metabolic diseases, such as inflammatory bowel disease, food allergies obesity and alcoholic liver disease In these diseases, inflammatory cytokines, reactive oxygen species andpathogenic bacteria have been found to impair intestinal TJ function..We have seen in literature review about Sijunzi-decoction and other benefit formulas that the current study of these kinds of benefit formulas is mainly concentrated in weak, elderly and low immunity and mainly reflected the effects of tonic nursing Qi. The function of get rid of pathogenic factors (in term of "Xie") for benefit formulas was rarely involved. Chinese traditional medicine has a saying "Righteousness exist, evil can not enter". But there is still no clear experimental data to support. What is the role of benefit formulas in the role of get rid of pathogenic factor is still unclear..Goodwin published the "leaky roof" in 1998, he said gastric mucosal barrier likened to the roof. Similarly, we can also be seen as the epithelial barrier is the "roof". Pathogenic bacterial infection firstly destroyed the cell tight junctions, resulting in the leaking of the roof and in the body incidence. Combine the features of the tonic of strengthen Qi, whether we can speculate: the tonic could repair the "roof",restore of damaged tight junctions and finally get rid of the pathogenic factors?.This study attempts to build the research system consisted with tonic, tight junctions and foreign pathogenic factors. Within this system, tight junction on behalf of "righteousness Qi ", foreign bacterial infection on behalf of "evils". We will study the barrier function changes, as well as the role played by the tonic when body was invaded by the pathogenic bacteria. Our study also provide the experimental basis for "Righteousness exist, evil can not enter".