BIOCHEMICAL AND HISTOCHEMICAL EXAMINATIONS ON LIPJD-BINDING PROTEINS (LBP), PEROXISOME PROLIFERATOR ACTIVATED RECEPTORS (PPAR) AND RETINOL RECEPTORS (RXR) IN KIDNEY.

1. 人正常与病变肾脏中flbp和PPARs表达的研究。(1)在正常人肾脏中，肝型（L-）脂肪酸结合蛋白（FABP）和心脏型FABP分别主要定位于肾小管上皮细胞（RTEC）的近端和远端细胞质中。PPAR-α主要存在于近端RTEC细胞质中，PPAR-γ主要存在于远端RTEC细胞质和收集管中。(2)重度缺氧的移植肾，部分近端rtec细胞质中L-FABP和PPAR-α表达升高。在间质性肾炎中，一些rtec近端可见L-FABP和PPAR-α的核染色，提示L-FABP与PPAR-α的相互作用。纯化的L-FABP含有内源性长链脂肪酸，可作为PPAR-α的配体和刺激剂。在间质性肾炎中，PPAR-α在浸润性嗜酸性细胞中表达，而在巨噬细胞中不表达。膜性肾病的核染色显示PPAR-α含量高于正常肾。人培养肾小管近端上皮细胞中lbp和PPARs表达的研究。(1)间接免疫荧光法和免疫印迹法显示L-FABP和PPAR-α在培养的人肾近端小管上皮细胞中表达。PAI-1在培养细胞中也有表达。(2)人近端肾小管细胞在含多种生长因子和生物活性分子的培养基中培养后，在浓度为250 ~ 600 ng/mL的培养基中检测到PAI-1抗原。在基础培养基中加入氢化可的松和肾上腺素可使培养细胞条件培养基中PAI- 1的浓度升高。缺氧似乎进一步诱导了生长培养基中培养细胞PAI-1的表达。临床变量与晚期肾脏疾病及血管疾病的关系分析。在高HDL-C血液透析患者中，胆固醇酯转移蛋白（CETP）是预防血管疾病的保护因子。亚甲基四氢叶酸还原酶（MTHFR）基因中一种常见的C677T突变与血清同型半胱氨酸水平升高有关，从而导致内皮细胞氧化应激。纯合突变体（TT基因型）在诱导血液透析时更年轻，透析持续时间更短，这表明高同型半胱氨酸血症可能与开始透析后肾损害的加速进展和死亡率有关。在糖尿病患者中，严重蛋白尿超过1000 mg/gCr的患者尿液中PAI-1浓度高于微量白蛋白尿患者，而血浆PAI-1水平在糖尿病肾病的进展过程中保持不变。尿PAI-1水平与尿NAG和糖水平呈正相关。少

1. Investigation on the expression ofLBPs and PPARs in normal and diseased human kidneys.(1) In normal human kidney, liver type (L-) fatty acid-binding protein (FABP) and heart-type FABP were predominantly localized in cytoplasm of proximal and distal renal tubular epithelial cells (RTEC), respectively. PPAR-α was mainly present in cytoplasm of proximal RTEC and PPAR-γ was present in cytoplasm of distal RTEC and collecting ducts.(2) As for transplanted kidneys suffering from severe hypoxia, the expressions of L-FABP and PPAR-α were increased in cytoplasm of some proximal RTECs. In interstitial nephritis, nuclear stainings for L-FABP and PPAR-α were found in some proximal RTECs, suggesting the interaction between L-FABP and PPAR-α. Purified L-FABP contained endogenously long-chain fatty acids which can serve as ligands, stimulators for PPAR-α. In interstitial nephritis, PPAR-α was expressed in infiltrating eosinophils but not macrophages. In membranous nephropathy, nuclear staining for … More PPAR-α was more frequent than normal kidney.2. Investigation on the expression of LBPs and PPARs in human cultured proximal renal tubular epithelial cells.(1) Indirect immunofluorescence method and immunoblotting revealed that L-FABP and PPAR-α were expressed in human cultured proximal renal tubular epithelial cells. PAI-1 was also expressed in the cultured cells.(2) PAI-1 antigen was detected in the medium of human cultured proximal renal tubular cells at a concentration of 250-600 ng/mL after the cells were cultured in the medium including several growth factors and bioactive molecules. Addition of hydrocortisone and epinephrine to the basic medium increased the concentration of PAI- 1 in the conditioned medium of the cultured cells. Hypoxia appeared to induce further the expression of PAI-1 in the cells cultured in the growth medium.3. Analysis of relationships between clinical variables and advanced renal disease and vascular disease.In hemodialysis patients with high HDL-C status, cholesteryl ester transfer protein (CETP) was a protective factor against vascular disease. A common C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene was associated with increased serum levels of homocysteine which causes oxidative stress to endothelial cells. The homozygous mutants (TT genotype) were younger at the induction of hemodialysis and had a shorter duration of dialysis, suggesting that hyperhomocysteinemia may be related to accelerated progression of renal damage and mortality after initiation of dialysis. Among diabetic patients, PAI-1 concentrations in urine were higher in those with severe proteinuria over 1000 mg/gCr than those with microalbuminuria, while plasma PAI-1 levels were unchanged during progression of diabetic nephropathy. Urinary PAI-1 levels were positively associated with urinary NAG and sugar levels. Less