Study on Reguratory Substance of ANCA Related-Nephritis

ANCA相关性肾炎调节物质的研究

• 批准号: 08671313
• 负责人: I-OKAWARA Akiko
• 金额: $ 0.9万
• 依托单位: National Institute of Infectious Diseases
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671313/
• 关键词: ANCA; Autoimmune diseases; MPO; Aseanostatin

1) The selection of model animalsUsually, MPO activity nor MPO-ANCA are detected in normal blood. However, both of them are detected at high level in rat plasma derived from anti-glomerulo basement membrane (GBM) antibody-induced-nephritis and adjuvant-induced-arthritis. GBM-induced-nephritis rat showed high protein urine, joint swelling was detected in paw injected adjuvant.2) The evaluation of aseanostatin, i-14 : 0 on improvement of adjuvant-induced-arthritisOral administration (20 mg/kg), or intraperitoneal administration (30 mg/kg) was continued to adjuvant-induced-arthritis rat for 18 days. MPO-ANCA level decreased near the normal level. On the other hand, the degree of joint swelling, change of weight of thymus and spleen, biochemical change of serum were hardly affected by administration of aseanostatin. Intraperitoneal administration of aseanostatin appeared effective on improvement of inhibition of body weight decrease, leukocyte increase, paw swelling, bone destruction, howe … More ver, similar result was detected in the group injected only solvent for 18 days. This phenomenon could be explained by the reason that injection of intraperitoneal induce inflammation at the site, then anti-inflammatory effect may produce. As a result, treatment effect of aseanostatin may be weak. Since measurement of aseanostatin as a fatty acid could not establish, concentration of aseanostatin could not clear exactly, it may be low level in serum. Moreover, effect of aseanostatin on improvement of GBM-induced-nephritis will investigate.Summary1) MPO-ANCA titer increased in serum derived from adjuvant-induced-arthritis rat.2) Administration of aseanostatin decreased MPO-ANCA titer near the normal level, however it's medical effect was not enough.3) Since MPO-ANCA is one of indicator of neutrophil activation, decrease of MPO-ANCA titer could reflect reduction of risk of arthritis. However, condition of arthrits was hardly improvement.4) Epitope analysis would need to clarify the relationship between induction of MPO-ANCA and arthritis. Less

1)模型动物的选择正常人血液中通常不检测MPO活性，也不检测MPO-ANCA。然而，在抗肾小球基底膜（GBM）抗体诱导的肾炎和抗炎药诱导的关节炎大鼠血浆中检测到高水平的这两种药物。GBM诱导的肾炎大鼠表现出高蛋白尿，注射抗炎药的足爪中检测到关节肿胀。2）评价aseanostatin，i-14：0对抗炎药诱导的关节炎的改善。MPO-ANCA水平下降至接近正常水平。而对小鼠关节肿胀程度、胸腺和脾脏重量变化、血清生化指标变化无明显影响。腹腔注射谷氨酰胺抑菌素对小鼠体重下降、白细胞增多、足肿胀、骨破坏、骨坏死、 ...更多信息 而仅注射溶剂18天的组也检测到类似的结果。这可能是由于腹腔注射引起局部炎症反应，从而产生抗炎作用。因此，aseanostatin的治疗效果可能较弱。由于无法建立脂肪酸形式的测定方法，因此无法准确测定血清中的谷氨酰胺酶抑制素浓度，可能存在低水平。结论1）实验性关节炎大鼠血清中MPO-ANCA滴度升高; 2）应用谷氨酰胺抑菌素后，MPO-ANCA滴度下降，接近正常水平，但其治疗效果不明显; 3）由于MPO-ANCA是中性粒细胞活化的指标之一，因此MPO-ANCA滴度的降低可反映关节炎风险的降低。4）表位分析需要进一步阐明MPO-ANCA的诱导与关节炎的关系。少

项目成果

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