阅读说明：本技术 溶血磷脂酰乙醇胺18:1在制备缓解、治疗炎症性肠病药物中的应用 (Application of lysophosphatidylethanolamine 18:1 in preparation of medicines for relieving and treating inflammatory bowel diseases ) 是由 高翔 林兆宇 周达远 于 2019-12-12 设计创作，主要内容包括：本发明属于医药领域,涉及溶血磷脂酰乙醇胺18:1在制备缓解、治疗炎症性肠病药物中的应用。本发明公开了溶血磷脂酰乙醇胺18:1通过增加肠道上皮屏障的稳定性,以致于缓解或治疗肠炎和炎症性肠病。是一种有效的治疗炎症性肠病的药物。(The invention belongs to the field of medicines, and relates to application of lysophosphatidylethanolamine 18:1 in preparation of medicines for relieving and treating inflammatory bowel diseases. The present invention discloses that lysophosphatidylethanolamine 18:1 can be used for relieving or treating enteritis and inflammatory bowel diseases by increasing the stability of intestinal epithelial barrier. Is an effective medicine for treating inflammatory bowel diseases.)

1. Application of lysophosphatidylethanolamine 18:1 in preparing a medicine for relieving intestinal inflammation.

2. The application of lysophosphatidylethanolamine 18:1 in preparing medicines for treating inflammatory bowel diseases.

Technical Field

The invention belongs to the field of medicines, and relates to lysophosphatidylethanolamine 18:1 for relieving occurrence and development of intestinal inflammation so as to prevent or treat enteritis and inflammatory bowel diseases; in particular to lysophosphatidylethanolamine 18:1 which can relieve or treat enteritis and inflammatory bowel diseases by increasing the stability of the epithelial barrier of the intestinal tract.

Background

With the increasing abundance of production materials, people's diet is refined, and the incidence of Inflammatory Bowel Disease (IBD) is increasing. Worldwide, the annual incidence of IBD in North America and Western Europe is high10/10⁵(ii) a In China, the annual incidence of IBD is 0.3/10 of 1950⁵Increased to 1.4/10 of 2002⁵And shows a tendency to rise year by year.

Inflammatory Bowel Disease (IBD), is an idiopathic inflammatory disease involving the colon and small intestine. Crohn's disease and ulcerative colitis are the major types of inflammatory bowel disease. Crohn's disease affects the small intestine, large intestine, mouth, esophagus, stomach and anus, as a non-continuous, full-thickness inflammation, most frequently affecting the terminal ileum, colon and perianal region; ulcerative colitis is a continuous inflammation of the mucosal and submucosal layers of the colon, and the disease usually involves the rectum and gradually spreads throughout the colon. Inflammatory bowel disease is often accompanied by symptoms of diarrhea, abdominal pain, tenesmus, abdominal mass, anemia, fever, malnutrition, and the like.

Lysophosphatidylethanolamine (LPE)18:1 is white powder, is extremely insoluble in water and is extremely soluble in chloroform. Molecular formula of C23H46NO7PC₂₃H₄₆NO₇P, the chemical structural formula is shown in the following figure (I). There is no report on the effect of lysophosphatidylethanolamine 18:1 in treating inflammatory bowel disease.

To date, the etiology of inflammatory bowel disease is unclear and effective as to means for further study. Recent studies have indicated that the onset of inflammatory bowel disease is closely related to the intestinal flora. In the case of intestinal inflammation, bacteria of the enterobacteriaceae family (in particular escherichia coli) exhibit an explosive growth; and the tungstate is used for specifically inhibiting the growth of escherichia coli, so that the intestinal inflammation is favorably improved. These studies point out that finding effective means to treat inflammatory bowel disease is imperative; it is also significant to find a new diagnosis and treatment method for inflammatory bowel disease.

Disclosure of Invention

The invention aims to provide a new application of lysophosphatidylethanolamine 18: 1.

The invention discloses application of lysophosphatidylethanolamine 18:1 in preparation of a medicine for relieving intestinal inflammation.

The invention discloses application of lysophosphatidylethanolamine 18:1 in preparation of a medicament for treating inflammatory bowel diseases.

Through screening of C.elegans on Keio monogenic deletion Escherichia coli bank and mouse experiments, the polymorphism of blc gene of Escherichia coli is found, wherein the gene blc exists^a251(protein Blc^E84) And has a correlation with inflammatory bowel disease. Subsequent studies found Blc^E84The protein is due to reduced binding to the lipid lysophosphatidylethanolamine 18: 1; stool samples from patients with inflammatory bowel disease also showed a significant decrease in the amount of lysophosphatidylethanolamine 18:1 in the patient's intestinal tract. The artificial supplementation of lysophosphatidylethanolamine 18:1 can reverse the expression of blc^E84Pathogenic bacteria of proteins (blc)^E84Bacteria) infection caused intestinal injury in mice.

Artificial supplementation of lysophosphatidylethanolamine 18:1 (20. mu. mol/L, 200. mu.L/mouse) can reverse blc^E84Intestinal injury in mice caused by bacterial infection.

Drawings

FIG. 1 shows that lysophosphatidylethanolamine 18:1 in feces is significantly reduced after mice are infected with pathogenic Escherichia coli;

FIG. 2 shows the down-regulation of lysophosphatidylethanolamine 18:1 in feces of patients with inflammatory bowel disease compared to normal.

FIG. 3 shows that the supplement of lysophosphatidylethanolamine 18:1 can improve the decrease of intestinal permeability of mice caused by the infection of pathogenic Escherichia coli;

FIG. 4 shows that the supplementation of lysophosphatidylethanolamine 18:1 up-regulates the decrease of the expression level of intestinal barrier-associated cell connexin;

FIG. 5 is a gray scale analysis statistic of FIG. 4;

FIG. 6 shows the localization of the supplemental lysophosphatidylethanolamine 18:1 remodeling gut tight junction protein Claudin-1;

FIG. 7 shows the localization of the supplemental lysophosphatidylethanolamine 18:1 remodelling intestinal tight junction protein ZO-1;

FIG. 8 shows the localization of the supplemental lysophosphatidylethanolamine 18:1 remodeling gut tight junction protein Occludin.

P is <0.05, compared with mice infected with pathogenic bacteria and mice infected with non-pathogenic bacteria; denotes p < 0.01; denotes p < 0.0001.

Detailed Description