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Prevention of inflammatory diseases by regulating the production of lipid mediators-basic and clinical studies

通过调节脂质介质的产生预防炎症性疾病——基础和临床研究

基本信息

批准号：
13470500
负责人：
OKUYAMA Harumi
金额：
$ 8.32万
依托单位：
Nagoya City University, Graduate School Pharmaceutical Sciences
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

项目摘要

Inflammatory diseases include allergy, cancers of the Western type and many kinds of so-called intractable diseases. We interpreted that persistent inflammation is a major cause for the increased incidence of these diseases in Japan in the past half a century, and that these inflammatory diseases could be prevented by regulating the production of inflammatory mediators. At present, no safe means has been found to regulate the production of peptide mediators. However, the amounts and activities of lipid mediators can be modified safely by reducing the intake of n-6 fatty acids and increasing that of n-3 fatty acids in foods.In animal experiments, reducing the content of linoleic acid (n-6) and increasing that of α-linolenic acid (n-3) or fish oil enriched with EPA (n-3) and DHA (n-3) were shown to suppress the productions and activites of lipid kidney was suppressed similarly, and some results from animal experiments are collected in this report.On the other hand, we collaborated with clinicians to perform clinical trials aimed at treating atopic dermatitis and colorectal tumors by lowering the n-6/-3 ratio of fatty acids in foods. Subjects with atopic dermatitis (n=76) were advised to select foods so as to lower the n-6/n-3 ratio of ingested fatty acids, and were followed for 2 years to find that this means is very promising for the improvement of hyper-allergic constitution. In the randomized control trial for the suppression of recurrence of colorectal polyps after polypectomy, the number of subjects participating in the trial has been increasing. When the number of subjects was 20 in each group, this method seemed to be promising, too.These results support our interpretation that increased linoleic acid intake (>2.5 times high compared with the level of 40 years ago, several-fold higher than the essential amount) and relative n-3 fatty acid deficiency are the major causes for the increases in the incidence of these diseases.

炎症性疾病包括过敏，西方类型的癌症和许多所谓的顽固性疾病。我们解释说，在过去的半个世纪里，持续的炎症是日本这些疾病发病率增加的主要原因，这些炎症性疾病可以通过调节炎症介质的产生来预防。目前，还没有找到安全的方法来调节多肽介质的产生。然而，通过减少食物中n-6脂肪酸的摄入和增加n-3脂肪酸的摄入，可以安全地改变脂质介质的数量和活性。动物实验表明，降低亚油酸（n-6）含量，增加α-亚麻酸（n-3）含量，或富含EPA （n-3）和DHA （n-3）的鱼油均可抑制脂质肾的生成和活性，本报告收集了部分动物实验结果。另一方面，我们与临床医生合作，通过降低食物中n-6/-3脂肪酸的比例，进行治疗特应性皮炎和结直肠肿瘤的临床试验。建议76例特应性皮炎患者选择食物以降低摄入脂肪酸的n-6/n-3比率，并随访2年，发现这种方法对改善超过敏体质非常有希望。在抑制结直肠息肉切除术后复发的随机对照试验中，参与试验的受试者数量不断增加。当每组受试者人数为20人时，这种方法似乎也很有前途。这些结果支持了我们的解释，即亚油酸摄入量的增加（与40年前相比增加2.5倍，比必需量高出数倍）和n-3脂肪酸的相对缺乏是这些疾病发病率增加的主要原因。