DEVELOPMENT OF SERUM-FABP ASSAY AND IT'S CLINICAL APPLICATION

血清FABP检测方法的研制及其临床应用

• 批准号: 04557126
• 负责人: ONO Teruo
• 金额: $ 4.93万
• 依托单位: NIIGATA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-04557126/
• 关键词: Fatty Acid-Binding Protein; H-FABP; I-FABP; I-15P; Myocardial Infarct; Serum Mark; L-FABP

We have succeeded in cloning of two FABP family new members. One is a I-15P from intestine and the other is c-FABP from rat skin. The deduced I-15P cDNA sequence of 127 amino acids was identical that of rat I-15P protein purified from rat intestinal epithelium. Northern blot analysis indicated that the same was deteceted in the ovary suggesting that I-15P or a homologous protein might in volved in the metabolism of steroids in steroid hormone-producing tissues. Another new family member, c-FABP exhibits 50 % identity to myelin P2 protein, adipocyte FABP and heat FABP.We have developed the assay methods of serum FABPs and tested whether serum FABP is available as a marker of damaged tissues. Serum I-FABP was measured in rats with intestinal ischemic condition. The I-FABP level increased rapidly at 1, 2, 4 and 8 hr after ligation of rat intestine. It also increased at 1 hr after a 30-min transient occlusion and then returned to a normal level. Histological studies supported I-FABP release from necrotic adsorptive epithelial cell. The results suggest that the I-FABP is a useful biochemical maker for intestinal ischemia, particularly in the early reversible phase. The serum H-FABP determinations performed on 9 patitents with acute myocardial infarct (AMI) demonstrated that 4 serum samples obtaining within 1.5 h after heart stroke were within normal level, whereas 5 serum samples obtained with more than 1.5 h after heart stroke were showed elevated H-FABP levels. However, it reached maximum levels faster than serum creatine kinase MB(CK-MB) and creatine phosphokinase (CKB) levels within 6 h after percutaneous transluminal coronary angioplasty (PTCA) treatment. The increase of urinary H-FABP after PTCA treatment is in a marked contrast to urinary CK-MB and CPK which has been scarcely detected. Thus, serum H-FABP is a useful biochemical marker for estimation of recirculation by PTCA treatment rather than the onset of heart stroke.

我们已经成功克隆了两个FABP家族的新成员。一种是来自肠道的I-15P，另一种是来自大鼠皮肤的c-FABP。推导的127个氨基酸的I-15P基因序列与从大鼠肠上皮中纯化的大鼠I-15P蛋白完全相同。Northern印迹分析表明，在卵巢中也检测到同样的结果，这表明I-15P或同源蛋白可能参与了类固醇激素产生组织中类固醇的代谢。另一种新的家族成员c-FABP与髓鞘P2蛋白、脂肪细胞FABP和热FABP有50%的同源性。我们建立了血清FABP的测定方法，并检验了血清FABP是否可以作为组织损伤的标志物。测定肠缺血大鼠血清I-FABP水平。大鼠肠结扎后1、2、4、8h，I-FABP水平迅速升高。在短暂阻断30分钟后1小时，它也升高，然后恢复到正常水平。组织学研究支持I-FABP从坏死的吸附上皮细胞释放。结果表明，I-FABP是肠缺血的有用生化标志物，尤其是在早期可逆性阶段。对9例急性心肌梗死(AMI)患者进行了血清H-FABP测定，其中4例在卒中后1.5小时内测定的血清H-FABP水平在正常范围内，5例在卒中后1.5小时以上的血清H-FABP水平升高。但在经皮冠状动脉腔内成形术(PTCA)治疗后6h内达到峰值的速度快于血清肌酸激酶MB(CK-MB)和肌酸磷酸激酶(CKB)水平。PTCA术后尿H-FABP的升高与很少检测到的尿CK-MB和CPK的升高形成明显的对比。因此，血清H-FABP是一种有用的生化标志物，可以用来评估PTCA治疗的再循环，而不是心脏病卒中的发生。

项目成果

Suzuki,T.: "Establishment of a human hepatoblastoma model in athymic nude mice:Producibility of fatty acid binding protein,α-fetoprotein and α_1-acid glycoprotein" Acta Pathol.Jan.42. 255-261 (1992)

Suzuki, T.：“在无胸腺裸鼠中建立人肝母细胞瘤模型：脂肪酸结合蛋白、α-胎蛋白和α_1-酸性糖蛋白的生产能力”Acta Pathol.Jan.42（1992）。

Aono,S.: "Detection of bilirubin binding proteins in the liver on a nitrocellulose membrane" Biomed.Res.13. 69-74 (1992)

Aono,S.：“硝酸纤维素膜上肝脏中胆红素结合蛋白的检测”Biomed.Res.13。

小野輝夫: "新生化学実験化学講座 脂肪酸結合タンパク質" 東京化学同人, 5 (1993)

小野照夫：《新实验化学课程：脂肪酸结合蛋白》东京化学同人，5（1993）

Sachiko Aono: "Detection of bilirubin-binding proteins in the liver on a nitrocellulose membrane" Biomedical Research. 13. 69-74 (1992)

Sachiko Aono：“在硝酸纤维素膜上检测肝脏中的胆红素结合蛋白”生物医学研究。

Tatsuo Kanda: "Intestinal fatty acid binding protein as as sensitive marker of intestinal ischemia" Digestive Disease and Sciences. 37. 1362-1367 (1992)

Tatsuo Kanda：“肠脂肪酸结合蛋白作为肠缺血的敏感标记”《消化疾病与科学》。