New Therapeutic omega-3 unsaturated fatty acid for nonspecific inflammatory colonic diseases.

用于非特异性炎症性结肠疾病的新型治疗性 omega-3 不饱和脂肪酸。

• 批准号: 07807125
• 负责人: NAKASAKI Hisao
• 金额: $ 1.15万
• 依托单位: Tokai University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07807125/
• 关键词: non specific inflammatory colonic disease; TNBS-induced colitis; omega-3 type fatty acid; fish oil

The causes of nonspecific inflammatory diseases of the intestinal tract--Crohn's disease, ulcerative colitis, and intestinal Behcet's disease--are unknown. The remedies for these afflictions are total parenteral nutrition and the administration of steroids and salazosulfa pyridine immunosppressants. It is known, however, that total parenteral nutrition over a long period leads to a decline in local immunocompetence, accompanied by disused atrophy of the intestinal tract. This produces expansion of an auxiliary lesion of the inflammatory diseases and delayd healing.The purposes of the research were as follow ;(1) (a) Preparatory development targeting the creation of an absorbable EPA,which has a superior antiinflammatory effects. (b) The establishment of preparatory technology for emulsification by the use of lecithin, and (c) the creation of an emulsion that includes omega-3 fat by mixing soybean oil and fish oil. (2) Examination of the effectiveness of the pervenous-administration met … More hod, by using the newly developed fat nutrient on diseased-animals' models. (3) Confirmation of the effect as a fat nutrient (a) by administering an appropriate mixture of fish oil to animal models, (b) by analyzing the fatty acid in the serum, and (c) by examining the histological findings and the state of the biological function of the intestinal mucous membranes.The results ;TPN solutions with various fatty acid compositions were administered. Soybean contains 6.9% omega-3 fatty acid and fish oil containns 32.1% of omega-3 fatty acid. The fat emulsions and their relative proportions used in the respective group were as follows :Group I : Soybean oil emulsion only.Group II : mixture of 75% soybean oil and 25% fish oil emulsion.Group III : mixture of 50% soybean oil and 50% fish oil emulsion.Group IV : mixture of 25% soybean oil and 75% fish oil emulsion.Group V : fish oil emulsion only.Group VI : no fat emulsion administered.After completion of the 7-day TPN period the rats were laparotomized under ether anesthesia. The degree of healing of ulcerative colitis was assessed by HE staining of the colitis region and grading in accordance with the criteria.The severity of colitis was least in Group II (containing 13.2% of omega-3 fatty acid), and was relatively greater in Group III,I,IV and VI in that order.Group II displayd a significantly lower degree of severity as compared with group VI according to the Dunnett multiple comparison method and also as compared with group V according to the Tukey multiple comparison method. The result indicates that administration of omega-3 essential fatty acids has an anti-inflammatory effect. Moreover, the results indicated that healing effects could not be expected from administration of fat emulsions containing only soybean oil (Group I).Further studies are necessary in order to ascertain the concentrations between appropriate fish oil dosages. Less

肠道非特异性炎症性疾病——克罗恩病、溃疡性结肠炎和肠道白塞氏病——的病因尚不清楚。这些疾病的治疗方法是全肠外营养以及使用类固醇和柳氮磺胺吡啶免疫抑制剂。但众所周知，长期全胃肠外营养会导致局部免疫能力下降，并伴有肠道废弃性萎缩。这会导致炎症性疾病的辅助病变扩大并延迟愈合。本研究的目的如下：(1)(a)以创建具有优异抗炎作用的可吸收EPA为目标的前期开发。 (b) 建立了使用卵磷脂的乳化制备技术，以及 (c) 通过混合大豆油和鱼油来制备含有 omega-3 脂肪的乳液。 (2) 通过在患病动物模型上使用新开发的脂肪营养素来检查静脉给药的有效性。 (3)作为脂肪营养素的效果的确认(a)通过向动物模型给予适当的鱼油混合物，(b)通过分析血清中的脂肪酸，以及(c)通过检查组织学结果和肠粘膜的生物功能状态。结果；给予具有各种脂肪酸组成的TPN溶液。大豆含有 6.9% 的 omega-3 脂肪酸，鱼油含有 32.1% 的 omega-3 脂肪酸。各组中使用的脂肪乳剂及其相对比例如下：第 I 组：仅大豆油乳剂。第 II 组：75% 大豆油和 25% 鱼油乳剂的混合物。第 III 组：50% 大豆油和 50% 鱼油乳剂的混合物。第 IV 组：25% 大豆油和 75% 鱼油乳剂的混合物。第 V 组：鱼油乳剂。 仅第VI组：不施用脂肪乳剂。7天TPN期结束后，在乙醚麻醉下对大鼠进行剖腹手术。通过对结肠炎区域进行HE染色并按照标准进行分级来评估溃疡性结肠炎的愈合程度。II组结肠炎的严重程度最轻（含有13.2%的omega-3脂肪酸），III、I、IV和VI组的结肠炎严重程度相对较高。根据Dunnett多重比较法，II组的严重程度明显低于VI组，并且与VI组相比，II组的结肠炎严重程度明显低于VI组。 根据Tukey多重比较法与V组进行比较。结果表明，施用omega-3必需脂肪酸具有抗炎作用。此外，结果表明仅含有大豆油的脂肪乳剂（第一组）的治疗效果无法预期。为了确定适当的鱼油剂量之间的浓度，有必要进行进一步的研究。较少的